{ "_meta": { "name": "GLP-1 and incretin drug clinical trials: structured summaries (Saciedad)", "description": "Randomized clinical trial publications on semaglutide, tirzepatide and other GLP-1 receptor agonists and incretin drugs, including some secondary analyses (extensions and post hoc analyses): population, number of participants, duration, primary outcome, primary result with confidence intervals when the abstract gives them, limitations (funding, design, population), DOI and trial registration. Neutral summaries in Spanish and English.", "license": "Creative Commons Attribution 4.0 International (CC BY 4.0)", "licenseUrl": "https://creativecommons.org/licenses/by/4.0/", "attribution": "Alex Gonzalez, saciedad.com (https://saciedad.com/datos/), CC BY 4.0", "version": "2026-10-07", "records": 53, "creator": "Alex Gonzalez", "publisher": "saciedad.com", "documentation": "https://saciedad.com/en/data/", "documentationEs": "https://saciedad.com/datos/", "upstreamSources": "Every record lists its own sources[]. Upstream sources (USDA FoodData Central, food composition tables and papers, Holt et al. 1995, EMA, FDA, AEMPS and other regulators, trial publications) remain under their own terms and must be cited too.", "notes": "One record per primary publication of a randomized clinical trial, including some secondary analyses (extensions, post hoc). Numbers not given in the abstract or full text are omitted, not approximated. drugIds refer to the drugs dataset. Text fields ending in Es are in Spanish, En in English." }, "records": [ { "id": "scale-maintenance", "acronym": "SCALE Maintenance", "title": "Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: The SCALE Maintenance randomized study", "titleEn": "SCALE Maintenance: liraglutide after diet-induced weight loss", "firstAuthor": "Wadden TA", "journal": "International Journal of Obesity", "year": 2013, "doi": "10.1038/ijo.2013.120", "url": "https://doi.org/10.1038/ijo.2013.120", "registryId": "NCT00781937", "drugIds": [ "liraglutida" ], "design": "rct", "populationEs": "422 adultos con IMC de 30 o más (o de 27 o más con comorbilidades) que perdieron al menos un 5 % del peso con una dieta baja en calorías antes de la aleatorización (un 6,0 % de media).", "populationEn": "422 adults with a BMI of 30 or more (or 27 or more with comorbidities) who lost at least 5% of their weight on a low-calorie diet before randomization (6.0% on average).", "nParticipants": 422, "durationWeeks": 56, "primaryOutcomeEs": "Tres variables principales desde la aleatorización hasta la semana 56, con liraglutida 3,0 mg diaria frente a placebo y consejo sobre dieta y ejercicio en ambos grupos: cambio porcentual del peso, proporción que mantuvo la pérdida inicial de al menos el 5 % y proporción que perdió al menos otro 5 %.", "primaryOutcomeEn": "Three primary outcomes from randomization to week 56, with liraglutide 3.0 mg daily versus placebo and diet and exercise counseling in both groups: percentage change in weight, proportion maintaining the initial loss of at least 5% and proportion losing at least another 5%.", "resultSummaryEs": "Tras perder un 6,0 % con la dieta, el peso bajó un 6,2 % adicional con liraglutida y un 0,2 % con placebo entre la aleatorización y la semana 56 (diferencia estimada de −6,1 puntos porcentuales; IC 95 %: −7,5 a −4,6). El 81,4 % con liraglutida mantuvo la pérdida inicial de al menos el 5 %, frente al 48,9 % con placebo (OR 4,8; IC 95 %: 3,0 a 7,7), y el 50,5 % frente al 21,8 % perdió al menos otro 5 % (OR 3,9; IC 95 %: 2,4 a 6,1). Hubo mejoras pequeñas, pero estadísticamente significativas, en varios factores de riesgo cardiometabólico. Los trastornos digestivos fueron más frecuentes con liraglutida, en su mayoría transitorios y leves o moderados.", "resultSummaryEn": "After losing 6.0% on the diet, weight fell by a further 6.2% with liraglutide and 0.2% with placebo between randomization and week 56 (estimated difference of −6.1 percentage points; 95% CI, −7.5 to −4.6). Of those on liraglutide, 81.4% maintained the initial loss of at least 5%, compared with 48.9% on placebo (OR 4.8; 95% CI, 3.0 to 7.7), and 50.5% versus 21.8% lost at least another 5% (OR 3.9; 95% CI, 2.4 to 6.1). There were small but statistically significant improvements in several cardiometabolic risk factors. Digestive disorders were more frequent with liraglutide, mostly transient and mild or moderate.", "limitationsEs": "Promovido por Novo Nordisk, según el registro del ensayo. Solo incluyó a quienes ya habían perdido al menos un 5 % con la dieta, lo que selecciona a personas con buena respuesta inicial. Estudió liraglutida diaria, no los fármacos semanales más recientes. El resumen no informa de lo que ocurre al suspender el tratamiento.", "limitationsEn": "Sponsored by Novo Nordisk, according to the trial registry. It only included people who had already lost at least 5% on the diet, which selects people with a good initial response. It studied daily liraglutide, not the newer weekly drugs. The abstract does not report what happens when treatment is stopped.", "sources": [ { "title": "Wadden TA, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013;37(11):1443-1451", "url": "https://doi.org/10.1038/ijo.2013.120", "publisher": "International Journal of Obesity", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 23812094 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/23812094/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "ClinicalTrials.gov NCT00781937: SCALE - Maintenance (sponsor and enrolment)", "url": "https://clinicaltrials.gov/study/NCT00781937", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SCALE Maintenance", "pageUrl": "https://saciedad.com/estudios/scale-maintenance/", "pageUrlEn": "https://saciedad.com/en/studies/scale-maintenance/" }, { "id": "scale-obesity-and-prediabetes", "acronym": "SCALE Obesity and Prediabetes", "title": "A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management", "titleEn": "SCALE Obesity and Prediabetes: liraglutide 3.0 mg (Saxenda)", "firstAuthor": "Pi-Sunyer X", "journal": "New England Journal of Medicine", "year": 2015, "doi": "10.1056/NEJMoa1411892", "url": "https://doi.org/10.1056/NEJMoa1411892", "registryId": "NCT01272219", "drugIds": [ "liraglutida" ], "design": "rct", "populationEs": "3731 adultos sin diabetes tipo 2 con IMC de 30 o más (o de 27 o más con dislipidemia o hipertensión); el 61,2 % tenía prediabetes y el peso medio inicial era de 106,2 kg.", "populationEn": "3,731 adults without type 2 diabetes with a BMI of 30 or more (or 27 or more with dyslipidemia or hypertension); 61.2% had prediabetes and mean starting weight was 106.2 kg.", "nParticipants": 3731, "durationWeeks": 56, "primaryOutcomeEs": "Cambio de peso, proporción con pérdida de al menos el 5 % y proporción con pérdida de más del 10 % a las 56 semanas.", "primaryOutcomeEn": "Change in weight, proportion losing at least 5% and proportion losing more than 10% at 56 weeks.", "resultSummaryEs": "Con liraglutida 3,0 mg diaria, junto con dieta y ejercicio, los participantes perdieron una media de 8,4 kg a las 56 semanas, frente a 2,8 kg con placebo; la diferencia fue de −5,6 kg (IC 95 %: −6,0 a −5,1). El 63,2 % perdió al menos el 5 % del peso, frente al 27,1 % con placebo, y el 33,1 % perdió más del 10 %, frente al 10,6 %. Los efectos adversos más frecuentes fueron náuseas y diarrea leves o moderadas; hubo eventos graves en el 6,2 % con liraglutida y el 5,0 % con placebo.", "resultSummaryEn": "With liraglutide 3.0 mg daily, plus diet and exercise, participants lost an average of 8.4 kg at 56 weeks, compared with 2.8 kg on placebo; the difference was −5.6 kg (95% CI, −6.0 to −5.1). Of those on liraglutide, 63.2% lost at least 5% of their weight, compared with 27.1% on placebo, and 33.1% lost more than 10%, compared with 10.6%. The most common adverse effects were mild or moderate nausea and diarrhea; serious events occurred in 6.2% on liraglutide and 5.0% on placebo.", "limitationsEs": "Financiado por Novo Nordisk. Los datos faltantes se imputaron con la última observación disponible, un método hoy considerado poco conservador. La pérdida de peso es menor que la observada después con semaglutida y tirzepatida, aunque no se compararon directamente.", "limitationsEn": "Funded by Novo Nordisk. Missing data were imputed with the last observation carried forward, a method now considered not very conservative. Weight loss is smaller than that later seen with semaglutide and tirzepatide, although they were not compared directly.", "sources": [ { "title": "Pi-Sunyer X, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22", "url": "https://doi.org/10.1056/NEJMoa1411892", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 26132939 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/26132939/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SCALE Obesity and Prediabetes", "pageUrl": "https://saciedad.com/estudios/scale-obesity-and-prediabetes/", "pageUrlEn": "https://saciedad.com/en/studies/scale-obesity-and-prediabetes/" }, { "id": "sustain-6", "acronym": "SUSTAIN-6", "title": "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes", "titleEn": "SUSTAIN-6: semaglutide (Ozempic) and heart outcomes in diabetes", "firstAuthor": "Marso SP", "journal": "New England Journal of Medicine", "year": 2016, "doi": "10.1056/NEJMoa1607141", "url": "https://doi.org/10.1056/NEJMoa1607141", "registryId": "NCT01720446", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "3297 adultos con diabetes tipo 2 y riesgo cardiovascular alto; el 83 % tenía enfermedad cardiovascular establecida, enfermedad renal crónica o ambas.", "populationEn": "3,297 adults with type 2 diabetes and high cardiovascular risk; 83% had established cardiovascular disease, chronic kidney disease or both.", "nParticipants": 3297, "durationWeeks": 104, "primaryOutcomeEs": "Primer evento cardiovascular mayor (muerte cardiovascular, infarto no mortal o ictus no mortal), con hipótesis principal de no inferioridad frente a placebo.", "primaryOutcomeEn": "First major cardiovascular event (cardiovascular death, nonfatal heart attack or nonfatal stroke), with a primary noninferiority hypothesis versus placebo.", "resultSummaryEs": "Con semaglutida subcutánea (0,5 o 1 mg semanal) durante una mediana de 2,1 años, el evento cardiovascular mayor ocurrió en el 6,6 % de los pacientes, frente al 8,9 % con placebo (hazard ratio 0,74; IC 95 %: 0,58 a 0,95; p < 0,001 para no inferioridad). El ictus no mortal fue menos frecuente (1,6 % frente a 2,7 %; HR 0,61; IC 95 %: 0,38 a 0,99), mientras que la muerte cardiovascular fue similar en ambos grupos. Las complicaciones de retinopatía diabética fueron más frecuentes con semaglutida (HR 1,76; IC 95 %: 1,11 a 2,78). Más pacientes abandonaron el tratamiento por efectos adversos, sobre todo digestivos.", "resultSummaryEn": "With subcutaneous semaglutide (0.5 or 1 mg once weekly) over a median of 2.1 years, a major cardiovascular event occurred in 6.6% of patients, compared with 8.9% on placebo (hazard ratio 0.74; 95% CI, 0.58 to 0.95; p < 0.001 for noninferiority). Nonfatal stroke was less frequent (1.6% versus 2.7%; HR 0.61; 95% CI, 0.38 to 0.99), while cardiovascular death was similar in both groups. Diabetic retinopathy complications were more frequent with semaglutide (HR 1.76; 95% CI, 1.11 to 2.78). More patients stopped treatment because of adverse effects, mainly digestive ones.", "limitationsEs": "Financiado por Novo Nordisk. Diseñado para demostrar no inferioridad, no superioridad; el número de eventos fue relativamente pequeño. La señal de retinopatía motivó estudios posteriores (FOCUS). Estudió las dosis de diabetes, no la de 2,4 mg.", "limitationsEn": "Funded by Novo Nordisk. Designed to show noninferiority, not superiority; the number of events was relatively small. The retinopathy signal prompted later studies (FOCUS). It studied the diabetes doses, not the 2.4 mg dose.", "sources": [ { "title": "Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834-1844", "url": "https://doi.org/10.1056/NEJMoa1607141", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 27633186 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/27633186/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SUSTAIN-6", "pageUrl": "https://saciedad.com/estudios/sustain-6/", "pageUrlEn": "https://saciedad.com/en/studies/sustain-6/" }, { "id": "step-1", "acronym": "STEP 1", "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity", "titleEn": "STEP 1: semaglutide 2.4 mg (Wegovy) for obesity without diabetes", "firstAuthor": "Wilding JPH", "journal": "New England Journal of Medicine", "year": 2021, "doi": "10.1056/NEJMoa2032183", "url": "https://doi.org/10.1056/NEJMoa2032183", "registryId": "NCT03548935", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "1961 adultos con IMC de 30 o más (o de 27 o más con al menos una comorbilidad relacionada con el peso), sin diabetes, en 16 países.", "populationEn": "1,961 adults with a BMI of 30 or more (or 27 or more with at least one weight-related comorbidity), without diabetes, in 16 countries.", "nParticipants": 1961, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción de participantes con una pérdida de al menos el 5 % a las 68 semanas.", "primaryOutcomeEn": "Percentage change in body weight and proportion of participants who lost at least 5% of their weight at 68 weeks.", "resultSummaryEs": "Semaglutida 2,4 mg semanal, junto con intervención sobre el estilo de vida, redujo el peso un 14,9 % de media a las 68 semanas, frente al 2,4 % con placebo; la diferencia estimada fue de −12,4 puntos porcentuales (IC 95 %: −13,4 a −11,5). El 86,4 % de los participantes con semaglutida perdió al menos el 5 % del peso, frente al 31,5 % con placebo, y el 50,5 % perdió al menos el 15 %, frente al 4,9 %. En kilos, la pérdida media fue de 15,3 kg frente a 2,6 kg. Las náuseas y la diarrea fueron los efectos adversos más frecuentes, en general leves o moderados y transitorios; el 4,5 % abandonó el tratamiento por síntomas digestivos, frente al 0,8 % con placebo.", "resultSummaryEn": "Semaglutide 2.4 mg once weekly, together with a lifestyle intervention, reduced weight by an average of 14.9% at 68 weeks, compared with 2.4% on placebo; the estimated difference was −12.4 percentage points (95% CI, −13.4 to −11.5). Of the participants on semaglutide, 86.4% lost at least 5% of their weight, compared with 31.5% on placebo, and 50.5% lost at least 15%, compared with 4.9%. In kilograms, the average loss was 15.3 kg versus 2.6 kg. Nausea and diarrhea were the most common adverse effects, generally mild or moderate and transient; 4.5% stopped treatment because of digestive symptoms, compared with 0.8% on placebo.", "limitationsEs": "Financiado por Novo Nordisk. Excluyó a personas con diabetes. Todos los participantes recibieron asesoramiento sobre dieta y ejercicio, algo que no siempre se replica en la práctica. No informa de lo que ocurre al suspender el fármaco (eso lo estudió la extensión STEP 1 y el ensayo STEP 4).", "limitationsEn": "Funded by Novo Nordisk. People with diabetes were excluded. All participants received diet and exercise counseling, which is not always replicated in practice. It does not report what happens when the drug is stopped (that was studied in the STEP 1 extension and the STEP 4 trial).", "sources": [ { "title": "Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002", "url": "https://doi.org/10.1056/NEJMoa2032183", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 33567185 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/33567185/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP 1", "pageUrl": "https://saciedad.com/estudios/step-1/", "pageUrlEn": "https://saciedad.com/en/studies/step-1/" }, { "id": "step-2", "acronym": "STEP 2", "title": "Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial", "titleEn": "STEP 2: semaglutide 2.4 mg (Wegovy) in type 2 diabetes", "firstAuthor": "Davies M", "journal": "The Lancet", "year": 2021, "doi": "10.1016/S0140-6736(21)00213-0", "url": "https://doi.org/10.1016/S0140-6736(21)00213-0", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "1210 adultos con diabetes tipo 2, IMC de 27 o más y HbA1c entre el 7 % y el 10 %, en 149 centros de 12 países.", "populationEn": "1,210 adults with type 2 diabetes, a BMI of 27 or more and an HbA1c between 7% and 10%, at 149 sites in 12 countries.", "nParticipants": 1210, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción con pérdida de al menos el 5 % a las 68 semanas, semaglutida 2,4 mg frente a placebo.", "primaryOutcomeEn": "Percentage change in body weight and proportion losing at least 5% at 68 weeks, semaglutide 2.4 mg versus placebo.", "resultSummaryEs": "En personas con diabetes tipo 2, semaglutida 2,4 mg semanal redujo el peso un 9,6 % a las 68 semanas, frente al 3,4 % con placebo; la diferencia estimada fue de −6,2 puntos porcentuales (IC 95 %: −7,3 a −5,2). Un tercer grupo con semaglutida 1,0 mg (la dosis de diabetes) sirvió de comparación activa. El 68,8 % de los participantes con 2,4 mg perdió al menos el 5 % del peso, frente al 28,5 % con placebo. Los efectos adversos digestivos, en su mayoría leves o moderados, afectaron al 63,5 % con 2,4 mg, al 57,5 % con 1,0 mg y al 34,3 % con placebo.", "resultSummaryEn": "In people with type 2 diabetes, semaglutide 2.4 mg once weekly reduced weight by 9.6% at 68 weeks, compared with 3.4% on placebo; the estimated difference was −6.2 percentage points (95% CI, −7.3 to −5.2). A third group on semaglutide 1.0 mg (the diabetes dose) served as an active comparison. Of the participants on 2.4 mg, 68.8% lost at least 5% of their weight, compared with 28.5% on placebo. Digestive adverse effects, mostly mild or moderate, affected 63.5% on 2.4 mg, 57.5% on 1.0 mg and 34.3% on placebo.", "limitationsEs": "Financiado por Novo Nordisk. La pérdida de peso fue menor que en STEP 1, algo habitual en personas con diabetes tipo 2. La comparación con semaglutida 1,0 mg no era el objetivo principal del ensayo.", "limitationsEn": "Funded by Novo Nordisk. Weight loss was smaller than in STEP 1, which is common in people with type 2 diabetes. The comparison with semaglutide 1.0 mg was not the main objective of the trial.", "sources": [ { "title": "Davies M, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). Lancet. 2021;397(10278):971-984", "url": "https://doi.org/10.1016/S0140-6736(21)00213-0", "publisher": "The Lancet", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 33667417 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/33667417/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP 2", "pageUrl": "https://saciedad.com/estudios/step-2/", "pageUrlEn": "https://saciedad.com/en/studies/step-2/" }, { "id": "step-3", "acronym": "STEP 3", "title": "Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial", "titleEn": "STEP 3: semaglutide (Wegovy) plus intensive behavioral therapy", "firstAuthor": "Wadden TA", "journal": "JAMA", "year": 2021, "doi": "10.1001/jama.2021.1831", "url": "https://doi.org/10.1001/jama.2021.1831", "registryId": "NCT03611582", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "611 adultos sin diabetes con IMC de 30 o más, o de 27 o más con al menos una comorbilidad, en 41 centros de Estados Unidos, aleatorizados a semaglutida 2,4 mg semanal (407) o placebo (204); 81,0 % mujeres, edad media de 46 años, peso medio de 105,8 kg e IMC medio de 38,0.", "populationEn": "611 adults without diabetes with a BMI of 30 or more, or 27 or more with at least one comorbidity, at 41 sites in the United States, randomized to semaglutide 2.4 mg once weekly (407) or placebo (204); 81.0% women, mean age 46 years, mean weight 105.8 kg and mean BMI 38.0.", "nParticipants": 611, "durationWeeks": 68, "primaryOutcomeEs": "Dos objetivos coprincipales a las 68 semanas: cambio porcentual del peso y proporción de participantes que perdieron al menos un 5 % del peso inicial, con semaglutida 2,4 mg semanal frente a placebo, ambos junto con una dieta baja en calorías las primeras 8 semanas y terapia conductual intensiva (30 sesiones de asesoramiento) durante las 68 semanas.", "primaryOutcomeEn": "Two co-primary objectives at 68 weeks: percentage change in weight and proportion of participants who lost at least 5% of their starting weight, with semaglutide 2.4 mg once weekly versus placebo, both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (30 counseling sessions) over the 68 weeks.", "resultSummaryEs": "A las 68 semanas, el peso cambió un −16,0 % con semaglutida y un −5,7 % con placebo; la diferencia estimada fue de −10,3 puntos porcentuales (IC 95 %: −12,0 a −8,6). Perdieron al menos un 5 % del peso el 86,6 % con semaglutida y el 47,6 % con placebo, al menos un 10 %, el 75,3 % y el 27,0 %, y al menos un 15 %, el 55,8 % y el 13,2 %. Son resultados del estimando de política de tratamiento, que incluye a todos los aleatorizados sigan o no el tratamiento; con el estimando de producto en ensayo, que supone que todos lo siguieron, la diferencia fue de −12,7 puntos porcentuales (IC 95 %: −14,3 a −11,0). Los efectos adversos digestivos afectaron al 82,8 % con semaglutida y al 63,2 % con placebo, y los motivaron el abandono del tratamiento en el 3,4 % con semaglutida, frente al 0 % con placebo.", "resultSummaryEn": "At 68 weeks, weight changed by −16.0% with semaglutide and −5.7% with placebo; the estimated difference was −10.3 percentage points (95% CI, −12.0 to −8.6). Weight fell by at least 5% in 86.6% on semaglutide and 47.6% on placebo, by at least 10% in 75.3% and 27.0%, and by at least 15% in 55.8% and 13.2%. These are results for the treatment-policy estimand, which includes everyone randomized whether or not they stayed on treatment; with the trial-product estimand, which assumes everyone stayed on it, the difference was −12.7 percentage points (95% CI, −14.3 to −11.0). Digestive adverse events affected 82.8% on semaglutide and 63.2% on placebo, and they led 3.4% on semaglutide to stop treatment, compared with 0% on placebo.", "limitationsEs": "Financiado por Novo Nordisk, que participó en el diseño, el análisis de los datos y la redacción. El programa de estilo de vida fue muy intensivo (30 visitas de asesoramiento y sustitutos de comidas las primeras 8 semanas), más de lo que suele ofrecerse en la práctica habitual. Excluyó a personas con diabetes, y la mayoría de los participantes eran mujeres (81,0 %) y blancos (76,1 %), todos en Estados Unidos. Duró 68 semanas y no evaluó qué ocurre al dejar el tratamiento.", "limitationsEn": "Funded by Novo Nordisk, which took part in the design, the data analysis and the writing. The lifestyle program was very intensive (30 counseling visits and meal replacements for the first 8 weeks), more than is usually offered in routine care. People with diabetes were excluded, and most participants were women (81.0%) and white (76.1%), all in the United States. It lasted 68 weeks and did not assess what happens after stopping treatment.", "sources": [ { "title": "Wadden TA, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325(14):1403-1413", "url": "https://doi.org/10.1001/jama.2021.1831", "publisher": "JAMA", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 33625476 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/33625476/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "Full text PMC7905697 (estimands, trial-product estimand result, race, meal replacements and role of the funder)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7905697/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT03611582 (registration and primary outcomes)", "url": "https://clinicaltrials.gov/study/NCT03611582", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "STEP 3", "pageUrl": "https://saciedad.com/estudios/step-3/", "pageUrlEn": "https://saciedad.com/en/studies/step-3/" }, { "id": "step-4", "acronym": "STEP 4", "title": "Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial", "titleEn": "STEP 4: continuing vs stopping semaglutide (Wegovy)", "firstAuthor": "Rubino D", "journal": "JAMA", "year": 2021, "doi": "10.1001/jama.2021.3224", "url": "https://doi.org/10.1001/jama.2021.3224", "registryId": "NCT03548987", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "902 adultos con IMC de 30 o más (o de 27 o más con al menos una comorbilidad relacionada con el peso), sin diabetes, en 73 centros de 10 países; 803 que alcanzaron 2,4 mg semanales tras 20 semanas de preinclusión fueron aleatorizados (2:1) a continuar con semaglutida (n = 535) o cambiar a placebo (n = 268), ambos con intervención sobre el estilo de vida.", "populationEn": "902 adults with a BMI of 30 or more (or 27 or more with at least one weight-related comorbidity), without diabetes, at 73 sites in 10 countries; 803 who reached 2.4 mg once weekly after a 20-week run-in were randomized (2:1) to continue semaglutide (n = 535) or switch to placebo (n = 268), both with a lifestyle intervention.", "nParticipants": 803, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal desde la semana 20 (aleatorización) hasta la semana 68, continuar con semaglutida 2,4 mg frente a cambiar a placebo.", "primaryOutcomeEn": "Percentage change in body weight from week 20 (randomization) to week 68, continuing semaglutide 2.4 mg versus switching to placebo.", "resultSummaryEs": "De la semana 20 a la 68, el peso cambió un −7,9 % en quienes siguieron con semaglutida y un +6,9 % en quienes pasaron a placebo (diferencia de −14,8 puntos porcentuales; IC 95 %: −16,0 a −13,5). Antes de la aleatorización, en las 20 semanas de preinclusión con semaglutida, habían perdido de media un 10,6 % del peso. El perímetro de cintura (−9,7 cm; IC 95 %: −10,9 a −8,5), la presión arterial sistólica (−3,9 mm Hg; IC 95 %: −5,8 a −2,0) y la puntuación de función física del SF-36 (2,5 puntos; IC 95 %: 1,6 a 3,3) también mejoraron al continuar frente a placebo. Los eventos digestivos afectaron al 49,1 % de quienes continuaron, frente al 26,1 % con placebo; los abandonos por efectos adversos fueron parecidos (2,4 % y 2,2 %).", "resultSummaryEn": "From week 20 to week 68, weight changed by −7.9% in those who stayed on semaglutide and by +6.9% in those switched to placebo (difference of −14.8 percentage points; 95% CI, −16.0 to −13.5). Before randomization, during the 20-week run-in on semaglutide, they had lost an average of 10.6% of their weight. Waist circumference (−9.7 cm; 95% CI, −10.9 to −8.5), systolic blood pressure (−3.9 mm Hg; 95% CI, −5.8 to −2.0) and the SF-36 physical functioning score (2.5 points; 95% CI, 1.6 to 3.3) also improved with continued treatment versus placebo. Digestive events affected 49.1% of those who continued, compared with 26.1% on placebo; discontinuations because of adverse effects were similar (2.4% and 2.2%).", "limitationsEs": "Financiado por Novo Nordisk, que participó en el diseño, el análisis y la redacción. La preinclusión abierta seleccionó a quienes toleraron la dosis de 2,4 mg (el 89,0 % de quienes la empezaron). Excluyó a personas con diabetes. Refleja una retirada completa a placebo, no una reducción progresiva ni un cambio a otro tratamiento.", "limitationsEn": "Funded by Novo Nordisk, which took part in the design, analysis and writing. The open-label run-in selected people who tolerated the 2.4 mg dose (89.0% of those who started it). People with diabetes were excluded. It reflects complete withdrawal to placebo, not a gradual dose reduction or a switch to another treatment.", "sources": [ { "title": "Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425", "url": "https://doi.org/10.1001/jama.2021.3224", "publisher": "JAMA", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 33755728 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/33755728/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC7988425 (funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7988425/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP 4", "pageUrl": "https://saciedad.com/estudios/step-4/", "pageUrlEn": "https://saciedad.com/en/studies/step-4/" }, { "id": "surpass-2", "acronym": "SURPASS-2", "title": "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes", "titleEn": "SURPASS-2: tirzepatide (Mounjaro) vs semaglutide in diabetes", "firstAuthor": "Frías JP", "journal": "New England Journal of Medicine", "year": 2021, "doi": "10.1056/NEJMoa2107519", "url": "https://doi.org/10.1056/NEJMoa2107519", "registryId": "NCT03987919", "drugIds": [ "tirzepatida", "semaglutida" ], "design": "rct", "populationEs": "1879 adultos con diabetes tipo 2 no controlada con metformina.", "populationEn": "1,879 adults with type 2 diabetes not controlled on metformin.", "nParticipants": 1879, "durationWeeks": 40, "primaryOutcomeEs": "Cambio de la HbA1c a las 40 semanas con tirzepatida 5, 10 o 15 mg frente a semaglutida 1 mg (no inferioridad y superioridad).", "primaryOutcomeEn": "Change in HbA1c at 40 weeks with tirzepatide 5, 10 or 15 mg versus semaglutide 1 mg (noninferiority and superiority).", "resultSummaryEs": "La HbA1c bajó 2,01, 2,24 y 2,30 puntos porcentuales con tirzepatida 5, 10 y 15 mg, frente a 1,86 puntos con semaglutida 1 mg; las diferencias fueron de −0,15 (IC 95 %: −0,28 a −0,03), −0,39 (IC 95 %: −0,51 a −0,26) y −0,45 puntos (IC 95 %: −0,57 a −0,32). Tirzepatida fue no inferior y superior a semaglutida en todas las dosis. La pérdida de peso fue mayor con tirzepatida: diferencias de −1,9, −3,6 y −5,5 kg frente a semaglutida. Los efectos adversos digestivos fueron parecidos entre grupos (náuseas del 17 al 22 % con tirzepatida y del 18 % con semaglutida).", "resultSummaryEn": "HbA1c fell by 2.01, 2.24 and 2.30 percentage points with tirzepatide 5, 10 and 15 mg, compared with 1.86 points with semaglutide 1 mg; the differences were −0.15 (95% CI, −0.28 to −0.03), −0.39 (95% CI, −0.51 to −0.26) and −0.45 points (95% CI, −0.57 to −0.32). Tirzepatide was noninferior and superior to semaglutide at every dose. Weight loss was greater with tirzepatide: differences of −1.9, −3.6 and −5.5 kg versus semaglutide. Digestive adverse effects were similar across groups (nausea in 17 to 22% on tirzepatide and 18% on semaglutide).", "limitationsEs": "Financiado por Eli Lilly. Comparó con semaglutida 1 mg, no con la dosis de 2 mg aprobada después para diabetes ni con la de 2,4 mg para obesidad. Diseño abierto en cuanto al dispositivo, aunque con evaluación enmascarada de la HbA1c.", "limitationsEn": "Funded by Eli Lilly. It compared tirzepatide with semaglutide 1 mg, not with the 2 mg dose later approved for diabetes or the 2.4 mg dose for obesity. Open-label with respect to the injection device, although HbA1c was assessed blinded.", "sources": [ { "title": "Frías JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503-515", "url": "https://doi.org/10.1056/NEJMoa2107519", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 34170647 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/34170647/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURPASS-2", "pageUrl": "https://saciedad.com/estudios/surpass-2/", "pageUrlEn": "https://saciedad.com/en/studies/surpass-2/" }, { "id": "surpass-3", "acronym": "SURPASS-3", "title": "Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial", "titleEn": "SURPASS-3: tirzepatide (Mounjaro) vs insulin degludec", "firstAuthor": "Ludvik B", "journal": "The Lancet", "year": 2021, "doi": "10.1016/S0140-6736(21)01443-4", "url": "https://doi.org/10.1016/S0140-6736(21)01443-4", "registryId": "NCT03882970", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "1444 adultos con diabetes tipo 2 no controlada con metformina, sola o con un inhibidor de SGLT2, que nunca habían usado insulina, con HbA1c del 7,0 al 10,5 % e IMC de 25 o más, en 122 centros de 13 países, aleatorizados a tirzepatida 5, 10 o 15 mg semanal o a insulina degludec diaria ajustada; se analizaron 1437 (358, 360, 359 y 360 por grupo), con HbA1c media inicial del 8,17 % y peso medio de 94,3 kg.", "populationEn": "1,444 adults with type 2 diabetes not controlled on metformin, alone or with an SGLT2 inhibitor, who had never used insulin, with HbA1c of 7.0 to 10.5% and a BMI of 25 or more, at 122 sites in 13 countries, randomized to tirzepatide 5, 10 or 15 mg once weekly or to titrated once-daily insulin degludec; 1,437 were analyzed (358, 360, 359 and 360 per group), with a mean starting HbA1c of 8.17% and mean weight of 94.3 kg.", "nParticipants": 1444, "durationWeeks": 52, "primaryOutcomeEs": "No inferioridad de tirzepatida 10 mg, 15 mg o ambas frente a insulina degludec en el cambio de la HbA1c a las 52 semanas, con un margen de 0,3 puntos porcentuales; la superioridad de todas las dosis en HbA1c y peso fue un objetivo secundario clave.", "primaryOutcomeEn": "Non-inferiority of tirzepatide 10 mg, 15 mg or both versus insulin degludec in the change in HbA1c at 52 weeks, with a margin of 0.3 percentage points; superiority of all doses in HbA1c and weight was a key secondary objective.", "resultSummaryEs": "A las 52 semanas, la HbA1c bajó 1,93, 2,20 y 2,37 puntos porcentuales con tirzepatida 5, 10 y 15 mg, y 1,34 puntos con insulina degludec; la diferencia frente a degludec fue de −0,59 a −1,04 puntos según la dosis, y todas las dosis fueron superiores. Alcanzaron una HbA1c inferior al 7,0 % entre el 82 y el 93 % con tirzepatida, frente al 61 % con degludec. El peso cambió entre −7,5 y −12,9 kg con tirzepatida y aumentó 2,3 kg con degludec (diferencia de −9,8 a −15,2 kg). Según el registro del ensayo, estas cifras excluyen los datos posteriores a dejar el fármaco o a empezar medicación de rescate, así que estiman el efecto en quienes siguieron el tratamiento. Hubo más náuseas (12 a 24 % frente a 2 %), diarrea (15 a 17 % frente a 4 %) y vómitos (6 a 10 % frente a 1 %) con tirzepatida, y más hipoglucemias por debajo de 54 mg/dl o graves con degludec (7 % frente a 1 a 2 %).", "resultSummaryEn": "At 52 weeks, HbA1c fell by 1.93, 2.20 and 2.37 percentage points with tirzepatide 5, 10 and 15 mg, and by 1.34 points with insulin degludec; the difference versus degludec ranged from −0.59 to −1.04 points by dose, and all doses were superior. HbA1c below 7.0% was reached by 82 to 93% on tirzepatide, compared with 61% on degludec. Weight changed by −7.5 to −12.9 kg with tirzepatide and rose by 2.3 kg with degludec (difference of −9.8 to −15.2 kg). According to the trial registry, these figures exclude data after stopping the drug or starting rescue medication, so they estimate the effect in those who stayed on treatment. There was more nausea (12 to 24% versus 2%), diarrhea (15 to 17% versus 4%) and vomiting (6 to 10% versus 1%) with tirzepatide, and more hypoglycemia below 54 mg/dL or severe with degludec (7% versus 1 to 2%).", "limitationsEs": "Financiado por Eli Lilly, fabricante de la tirzepatida. Fue un ensayo abierto: participantes e investigadores sabían qué tratamiento recibía cada uno. Comparó con una insulina ajustada a una glucosa en ayunas inferior a 5,0 mmol/l (90 mg/dl), no con otro agonista GLP-1, y con la insulina el peso aumentó, lo que agranda la diferencia en kilos. Solo incluyó a personas que tomaban metformina y nunca habían usado insulina, y duró 52 semanas. Dejar el tratamiento por efectos adversos fue más frecuente con tirzepatida que con degludec.", "limitationsEn": "Funded by Eli Lilly, the maker of tirzepatide. It was an open-label trial: participants and investigators knew which treatment each person received. It compared tirzepatide with insulin titrated to a fasting glucose below 5.0 mmol/L (90 mg/dL), not with another GLP-1 receptor agonist, and weight rose on insulin, which widens the difference in kilograms. It only included people taking metformin who had never used insulin, and it lasted 52 weeks. Stopping treatment because of adverse events was more common with tirzepatide than with degludec.", "sources": [ { "title": "Ludvik B, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598", "url": "https://doi.org/10.1016/S0140-6736(21)01443-4", "publisher": "The Lancet", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 34370970 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/34370970/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT03882970 (results: analysis population of the HbA1c and weight outcomes)", "url": "https://clinicaltrials.gov/study/NCT03882970", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "SURPASS-3", "pageUrl": "https://saciedad.com/estudios/surpass-3/", "pageUrlEn": "https://saciedad.com/en/studies/surpass-3/" }, { "id": "step-1-extension", "acronym": "STEP 1 (extensión)", "acronymEn": "STEP 1 (extension)", "title": "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension", "titleEn": "STEP 1 extension: weight regain after stopping semaglutide", "firstAuthor": "Wilding JPH", "journal": "Diabetes, Obesity and Metabolism", "year": 2022, "doi": "10.1111/dom.14725", "url": "https://doi.org/10.1111/dom.14725", "registryId": "NCT03548935", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "327 participantes de STEP 1 (adultos con IMC de 30 o más, o de 27 o más con al menos una comorbilidad, sin diabetes) que completaron las 68 semanas de tratamiento y fueron seguidos un año más sin tratamiento; subgrupo de centros de Canadá, Alemania, Reino Unido, Estados Unidos y Japón.", "populationEn": "327 STEP 1 participants (adults with a BMI of 30 or more, or 27 or more with at least one comorbidity, without diabetes) who completed the 68 weeks of treatment and were followed for another year off treatment; a subgroup from sites in Canada, Germany, the United Kingdom, the United States and Japan.", "nParticipants": 327, "durationWeeks": 120, "primaryOutcomeEs": "Análisis exploratorio del cambio de peso y de factores de riesgo cardiometabólico desde la semana 68 (fin del tratamiento con semaglutida 2,4 mg o placebo y de la intervención sobre el estilo de vida) hasta la semana 120.", "primaryOutcomeEn": "Exploratory analysis of the change in weight and cardiometabolic risk factors from week 68 (end of treatment with semaglutide 2.4 mg or placebo and of the lifestyle intervention) to week 120.", "resultSummaryEs": "Entre la semana 0 y la 68, el peso bajó de media un 17,3 % con semaglutida y un 2,0 % con placebo. Un año después de suspender el tratamiento y la intervención sobre el estilo de vida, los participantes que habían recibido semaglutida recuperaron 11,6 puntos porcentuales del peso perdido, frente a 1,9 con placebo, lo que dejó una pérdida neta del 5,6 % y del 0,1 %, respectivamente, en la semana 120. La mayoría de las mejoras cardiometabólicas volvieron hacia los valores iniciales. Los autores lo resumen como una recuperación de dos tercios de la pérdida previa.", "resultSummaryEn": "From week 0 to week 68, weight fell by an average of 17.3% with semaglutide and 2.0% with placebo. One year after treatment and the lifestyle intervention were stopped, participants who had received semaglutide regained 11.6 percentage points of the weight they had lost, compared with 1.9 on placebo, leaving a net loss of 5.6% and 0.1%, respectively, at week 120. Most cardiometabolic improvements drifted back toward baseline values. The authors sum this up as regaining two thirds of the prior loss.", "limitationsEs": "Financiado por Novo Nordisk. Todos los análisis son exploratorios y el subgrupo es pequeño (327 de 1961 participantes). Se suspendió a la vez el fármaco y la intervención sobre el estilo de vida, por lo que no separa el efecto de cada uno. Refleja una retirada completa, no una reducción progresiva ni un cambio a otro tratamiento.", "limitationsEn": "Funded by Novo Nordisk. All analyses are exploratory and the subgroup is small (327 of 1,961 participants). The drug and the lifestyle intervention were stopped at the same time, so the effect of each cannot be separated. It reflects complete withdrawal, not a gradual dose reduction or a switch to another treatment.", "sources": [ { "title": "Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564", "url": "https://doi.org/10.1111/dom.14725", "publisher": "Diabetes, Obesity and Metabolism", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 35441470 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/35441470/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC9542252 (methods, funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9542252/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP 1 (extensión)", "pageUrl": "https://saciedad.com/estudios/step-1-extension/", "pageUrlEn": "https://saciedad.com/en/studies/step-1-extension/" }, { "id": "step-5", "acronym": "STEP 5", "title": "Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial", "titleEn": "STEP 5: two years of semaglutide 2.4 mg (Wegovy) for obesity", "firstAuthor": "Garvey WT", "journal": "Nature Medicine", "year": 2022, "doi": "10.1038/s41591-022-02026-4", "url": "https://doi.org/10.1038/s41591-022-02026-4", "registryId": "NCT03693430", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "304 adultos con obesidad, o con sobrepeso y al menos una comorbilidad relacionada con el peso, sin diabetes, en 41 centros de cinco países (Canadá, España, Estados Unidos, Hungría e Italia), aleatorizados a semaglutida 2,4 mg semanal (152) o placebo (152); 77,6 % mujeres, edad media de 47,3 años, IMC medio de 38,5 y peso medio de 106,0 kg.", "populationEn": "304 adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes, at 41 sites in five countries (Canada, Hungary, Italy, Spain and the United States), randomized to semaglutide 2.4 mg once weekly (152) or placebo (152); 77.6% women, mean age 47.3 years, mean BMI 38.5 and mean weight 106.0 kg.", "nParticipants": 304, "durationWeeks": 104, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción de participantes que perdieron al menos un 5 % del peso a las 104 semanas (dos años) con semaglutida 2,4 mg semanal frente a placebo, ambos con intervención conductual.", "primaryOutcomeEn": "Percentage change in body weight and proportion of participants who lost at least 5% of their weight at 104 weeks (two years) with semaglutide 2.4 mg once weekly versus placebo, both with a behavioral intervention.", "resultSummaryEs": "A las 104 semanas, el peso cambió un −15,2 % con semaglutida 2,4 mg y un −2,6 % con placebo; la diferencia estimada fue de −12,6 puntos porcentuales (IC 95 %: −15,3 a −9,8). El 77,1 % de los participantes con semaglutida perdió al menos el 5 % del peso, frente al 34,4 % con placebo. El análisis principal incluyó a todos los aleatorizados, con independencia de que dejaran el tratamiento o recibieran otra intervención (estimando de política de tratamiento), y el 92,8 % completó el ensayo. Los efectos adversos digestivos, en su mayoría leves o moderados, fueron más frecuentes con semaglutida (82,2 % frente a 53,9 %).", "resultSummaryEn": "At 104 weeks, weight changed by −15.2% with semaglutide 2.4 mg and −2.6% with placebo; the estimated difference was −12.6 percentage points (95% CI, −15.3 to −9.8). Of the participants on semaglutide, 77.1% lost at least 5% of their weight, compared with 34.4% on placebo. The main analysis included everyone who was randomized, whether or not they stopped treatment or received another intervention (treatment-policy estimand), and 92.8% completed the trial. Digestive adverse effects, mostly mild or moderate, were more frequent with semaglutide (82.2% versus 53.9%).", "limitationsEs": "Financiado por Novo Nordisk, que diseñó el ensayo, supervisó su realización y recogió y analizó los datos. Muestra pequeña (304 participantes), con mayoría de mujeres y de personas blancas (93,1 %). Excluyó a personas con diabetes. Todos los participantes recibieron intervención conductual. No informa de lo que ocurre al suspender el fármaco después de los dos años.", "limitationsEn": "Funded by Novo Nordisk, which designed the trial, oversaw its conduct and collected and analyzed the data. Small sample (304 participants), mostly women and mostly white (93.1%). People with diabetes were excluded. All participants received a behavioral intervention. It does not report what happens when the drug is stopped after the two years.", "sources": [ { "title": "Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-2091", "url": "https://doi.org/10.1038/s41591-022-02026-4", "publisher": "Nature Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 36216945 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/36216945/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC9556320 (sites, estimands and funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9556320/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP 5", "pageUrl": "https://saciedad.com/estudios/step-5/", "pageUrlEn": "https://saciedad.com/en/studies/step-5/" }, { "id": "step-8", "acronym": "STEP 8", "title": "Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial", "titleEn": "STEP 8: semaglutide (Wegovy) vs liraglutide (Saxenda)", "firstAuthor": "Rubino DM", "journal": "JAMA", "year": 2022, "doi": "10.1001/jama.2021.23619", "url": "https://doi.org/10.1001/jama.2021.23619", "registryId": "NCT04074161", "drugIds": [ "semaglutida", "liraglutida" ], "design": "rct", "populationEs": "338 adultos con IMC de 30 o más (o de 27 o más con al menos una comorbilidad relacionada con el peso), sin diabetes, en 19 centros de Estados Unidos, aleatorizados a semaglutida 2,4 mg semanal (126), liraglutida 3,0 mg diaria (127) o placebo (85, dos grupos de placebo analizados juntos); edad media de 49 años, 78,4 % mujeres, peso medio de 104,5 kg e IMC medio de 37,5.", "populationEn": "338 adults with a BMI of 30 or more (or 27 or more with at least one weight-related comorbidity), without diabetes, at 19 sites in the United States, randomized to semaglutide 2.4 mg once weekly (126), liraglutide 3.0 mg once daily (127) or placebo (85, two placebo groups analyzed together); mean age 49 years, 78.4% women, mean weight 104.5 kg and mean BMI 37.5.", "nParticipants": 338, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal a las 68 semanas con semaglutida 2,4 mg semanal frente a liraglutida 3,0 mg diaria, ambas con dieta y actividad física. La comparación entre los dos fármacos fue abierta; cada uno era doble ciego frente a su placebo.", "primaryOutcomeEn": "Percentage change in body weight at 68 weeks with semaglutide 2.4 mg once weekly versus liraglutide 3.0 mg once daily, both with diet and physical activity. The comparison between the two drugs was open-label; each was double-blinded against its own placebo.", "resultSummaryEs": "A las 68 semanas, el peso cambió un −15,8 % con semaglutida y un −6,4 % con liraglutida (diferencia de −9,4 puntos porcentuales; IC 95 %: −12,0 a −6,8); con placebo, un −1,9 %. Perdieron al menos el 10 % del peso el 70,9 % con semaglutida y el 25,6 % con liraglutida, al menos el 15 %, el 55,6 % y el 12,0 %, y al menos el 20 %, el 38,5 % y el 6,0 %. Los resultados incluyen a quienes dejaron el tratamiento (estimando de política de tratamiento). Dejaron el tratamiento por cualquier motivo el 13,5 % con semaglutida y el 27,6 % con liraglutida; los efectos adversos digestivos fueron parecidos (84,1 % y 82,7 %).", "resultSummaryEn": "At 68 weeks, weight changed by −15.8% with semaglutide and −6.4% with liraglutide (difference of −9.4 percentage points; 95% CI, −12.0 to −6.8); on placebo it changed by −1.9%. At least 10% of weight was lost by 70.9% on semaglutide and 25.6% on liraglutide, at least 15% by 55.6% and 12.0%, and at least 20% by 38.5% and 6.0%. The results include people who stopped treatment (treatment-policy estimand). Treatment was stopped for any reason by 13.5% on semaglutide and 27.6% on liraglutide; digestive adverse effects were similar (84.1% and 82.7%).", "limitationsEs": "Financiado por Novo Nordisk, fabricante de los dos fármacos, que participó en el diseño, el análisis y la redacción. La comparación entre semaglutida y liraglutida fue abierta: los participantes sabían cuál de los dos recibían. Muestra pequeña, en un solo país y sin personas con diabetes. Quien no toleraba 2,4 mg de semaglutida podía seguir con 1,7 mg, mientras que quien no toleraba 3,0 mg de liraglutida debía interrumpirla y podía reiniciar la escalada de dosis, lo que puede influir en los abandonos.", "limitationsEn": "Funded by Novo Nordisk, the maker of both drugs, which took part in the design, analysis and writing. The comparison between semaglutide and liraglutide was open-label: participants knew which of the two they were getting. Small sample, in a single country and without people with diabetes. People who could not tolerate 2.4 mg of semaglutide could continue on 1.7 mg, whereas people who could not tolerate 3.0 mg of liraglutide had to stop it and could restart the dose escalation, which may influence discontinuations.", "sources": [ { "title": "Rubino DM, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138-150", "url": "https://doi.org/10.1001/jama.2021.23619", "publisher": "JAMA", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 35015037 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/35015037/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC8753508 (estimands and funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8753508/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP 8", "pageUrl": "https://saciedad.com/estudios/step-8/", "pageUrlEn": "https://saciedad.com/en/studies/step-8/" }, { "id": "surmount-1", "acronym": "SURMOUNT-1", "title": "Tirzepatide Once Weekly for the Treatment of Obesity", "titleEn": "SURMOUNT-1: tirzepatide (Zepbound) for obesity without diabetes", "firstAuthor": "Jastreboff AM", "journal": "New England Journal of Medicine", "year": 2022, "doi": "10.1056/NEJMoa2206038", "url": "https://doi.org/10.1056/NEJMoa2206038", "registryId": "NCT04184622", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "2539 adultos con IMC de 30 o más (o de 27 o más con al menos una complicación relacionada con el peso), sin diabetes; peso medio inicial de 104,8 kg.", "populationEn": "2,539 adults with a BMI of 30 or more (or 27 or more with at least one weight-related complication), without diabetes; mean starting weight of 104.8 kg.", "nParticipants": 2539, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción con pérdida de al menos el 5 % a las 72 semanas, para cada dosis de tirzepatida frente a placebo.", "primaryOutcomeEn": "Percentage change in body weight and proportion losing at least 5% at 72 weeks, for each tirzepatide dose versus placebo.", "resultSummaryEs": "A las 72 semanas, el cambio medio de peso fue del −15,0 % con tirzepatida 5 mg (IC 95 %: −15,9 a −14,2), del −19,5 % con 10 mg (IC 95 %: −20,4 a −18,5) y del −20,9 % con 15 mg (IC 95 %: −21,8 a −19,9), frente al −3,1 % con placebo (IC 95 %: −4,3 a −1,9). Perdió al menos el 5 % del peso el 85 %, el 89 % y el 91 % de los participantes con 5, 10 y 15 mg, frente al 35 % con placebo. Con 10 y 15 mg, el 50 % y el 57 % perdió al menos el 20 % del peso, frente al 3 % con placebo. Los efectos adversos más frecuentes fueron digestivos, en su mayoría leves o moderados y concentrados en la fase de escalada de dosis; llevaron a abandonar el tratamiento al 4,3 %, 7,1 % y 6,2 % con tirzepatida y al 2,6 % con placebo.", "resultSummaryEn": "At 72 weeks, the mean change in weight was −15.0% with tirzepatide 5 mg (95% CI, −15.9 to −14.2), −19.5% with 10 mg (95% CI, −20.4 to −18.5) and −20.9% with 15 mg (95% CI, −21.8 to −19.9), compared with −3.1% on placebo (95% CI, −4.3 to −1.9). At least 5% of body weight was lost by 85%, 89% and 91% of participants on 5, 10 and 15 mg, compared with 35% on placebo. On 10 and 15 mg, 50% and 57% lost at least 20% of their weight, compared with 3% on placebo. The most common adverse effects were digestive, mostly mild or moderate and concentrated in the dose-escalation phase; they led 4.3%, 7.1% and 6.2% of participants on tirzepatide and 2.6% on placebo to stop treatment.", "limitationsEs": "Financiado por Eli Lilly. Excluyó a personas con diabetes. No comparó directamente con semaglutida (eso lo hizo SURMOUNT-5). Los resultados reflejan tratamiento continuado con apoyo sobre el estilo de vida.", "limitationsEn": "Funded by Eli Lilly. People with diabetes were excluded. It did not compare tirzepatide directly with semaglutide (SURMOUNT-5 did). The results reflect continued treatment with lifestyle support.", "sources": [ { "title": "Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216", "url": "https://doi.org/10.1056/NEJMoa2206038", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 35658024 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/35658024/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-1", "pageUrl": "https://saciedad.com/estudios/surmount-1/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-1/" }, { "id": "oasis-1", "acronym": "OASIS 1", "title": "Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial", "titleEn": "OASIS 1: oral semaglutide 50 mg, a daily pill, for obesity", "firstAuthor": "Knop FK", "journal": "The Lancet", "year": 2023, "doi": "10.1016/S0140-6736(23)01185-6", "url": "https://doi.org/10.1016/S0140-6736(23)01185-6", "registryId": "NCT05035095", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "667 adultos sin diabetes tipo 2 con IMC de 30 o más, o de 27 o más con complicaciones o comorbilidades relacionadas con el peso, en 50 centros ambulatorios de nueve países de Asia, Europa y Norteamérica, aleatorizados a semaglutida oral 50 mg (334) o placebo (333).", "populationEn": "667 adults without type 2 diabetes with a BMI of 30 or more, or 27 or more with weight-related complications or comorbidities, at 50 outpatient clinics in nine countries in Asia, Europe and North America, randomized to oral semaglutide 50 mg (334) or placebo (333).", "nParticipants": 667, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción que redujo al menos un 5 % el peso a las 68 semanas con semaglutida oral diaria, escalada hasta 50 mg, frente a placebo, ambos con intervención sobre el estilo de vida.", "primaryOutcomeEn": "Percentage change in body weight and proportion reducing their weight by at least 5% at 68 weeks with daily oral semaglutide, escalated to 50 mg, versus placebo, both with a lifestyle intervention.", "resultSummaryEs": "A las 68 semanas, el peso cambió un −15,1 % con semaglutida oral 50 mg y un −2,4 % con placebo; la diferencia estimada fue de −12,7 puntos porcentuales (IC 95 %: −14,2 a −11,3). Redujeron el peso al menos un 5 % el 85 % con semaglutida y el 26 % con placebo, al menos un 10 %, el 69 % y el 12 %, al menos un 15 %, el 54 % y el 6 %, y al menos un 20 %, el 34 % y el 3 %. El análisis principal incluyó a todos los aleatorizados, con independencia de que dejaran el tratamiento o usaran otras terapias para perder peso (análisis por intención de tratar). Los efectos adversos digestivos, en su mayoría leves o moderados, afectaron al 80 % con semaglutida y al 46 % con placebo.", "resultSummaryEn": "At 68 weeks, weight changed by −15.1% with oral semaglutide 50 mg and −2.4% with placebo; the estimated difference was −12.7 percentage points (95% CI, −14.2 to −11.3). Weight fell by at least 5% in 85% on semaglutide and 26% on placebo, by at least 10% in 69% and 12%, by at least 15% in 54% and 6%, and by at least 20% in 34% and 3%. The main analysis included everyone who was randomized, whether or not they stopped treatment or used other weight-loss therapies (intention-to-treat analysis). Digestive adverse effects, mostly mild or moderate, affected 80% on semaglutide and 46% on placebo.", "limitationsEs": "Financiado por Novo Nordisk. Excluyó a personas con diabetes tipo 2. Estudió una dosis diaria de 50 mg, distinta de la de 25 mg evaluada en OASIS 4, y no se comparó con la semaglutida inyectable. Los porcentajes de participantes que alcanzaron cada umbral se calcularon sobre quienes tenían datos a las 68 semanas (317 con semaglutida y 295 con placebo).", "limitationsEn": "Funded by Novo Nordisk. People with type 2 diabetes were excluded. It studied a daily dose of 50 mg, different from the 25 mg dose evaluated in OASIS 4, and it was not compared with injectable semaglutide. The percentages of participants reaching each threshold were calculated among those with data at 68 weeks (317 on semaglutide and 295 on placebo).", "sources": [ { "title": "Knop FK, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402(10403):705-719", "url": "https://doi.org/10.1016/S0140-6736(23)01185-6", "publisher": "The Lancet", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 37385278 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/37385278/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "OASIS 1", "pageUrl": "https://saciedad.com/estudios/oasis-1/", "pageUrlEn": "https://saciedad.com/en/studies/oasis-1/" }, { "id": "retatrutide-phase-2-obesity", "acronym": "Retatrutida fase 2 (obesidad)", "acronymEn": "Retatrutide phase 2 (obesity)", "title": "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial", "titleEn": "Retatrutide phase 2 trial in obesity: results at 48 weeks", "firstAuthor": "Jastreboff AM", "journal": "New England Journal of Medicine", "year": 2023, "doi": "10.1056/NEJMoa2301972", "url": "https://doi.org/10.1056/NEJMoa2301972", "registryId": "NCT04881760", "drugIds": [ "retatrutida" ], "design": "rct", "populationEs": "338 adultos con IMC de 30 o más (o de 27 a 30 con al menos una enfermedad relacionada con el peso), sin diabetes.", "populationEn": "338 adults with a BMI of 30 or more (or 27 to 30 with at least one weight-related condition), without diabetes.", "nParticipants": 338, "durationWeeks": 48, "primaryOutcomeEs": "Cambio porcentual del peso corporal a las 24 semanas; el cambio a las 48 semanas fue un objetivo secundario.", "primaryOutcomeEn": "Percentage change in body weight at 24 weeks; the change at 48 weeks was a secondary objective.", "resultSummaryEs": "En este ensayo de fase 2, retatrutida (agonista de los receptores GIP, GLP-1 y glucagón) redujo el peso a las 48 semanas un 24,2 % con 12 mg semanales, un 22,8 % con 8 mg, un 17,1 % con 4 mg y un 8,7 % con 1 mg, frente al 2,1 % con placebo. A las 24 semanas (objetivo principal) la reducción fue del 17,5 % con 12 mg frente al 1,6 % con placebo. Los efectos adversos más frecuentes fueron digestivos y dependientes de la dosis. Los intervalos de confianza no figuran en el resumen del artículo.", "resultSummaryEn": "In this phase 2 trial, retatrutide (a GIP, GLP-1 and glucagon receptor agonist) reduced weight at 48 weeks by 24.2% with 12 mg once weekly, 22.8% with 8 mg, 17.1% with 4 mg and 8.7% with 1 mg, compared with 2.1% on placebo. At 24 weeks (the primary outcome), the reduction was 17.5% with 12 mg versus 1.6% on placebo. The most common adverse effects were digestive and dose-dependent. Confidence intervals are not given in the paper’s abstract.", "limitationsEs": "Ensayo de fase 2 con pocos participantes por grupo y financiado por Eli Lilly; los dos primeros ensayos de fase 3 (TRIUMPH-1 y TRIUMPH-2) se publicaron en revistas revisadas por pares el 29 de septiembre de 2026; TRIUMPH-3 y TRIUMPH-4 solo se habían comunicado por nota de prensa en la fecha de revisión. El fármaco no está aprobado en ningún país.", "limitationsEn": "A phase 2 trial with few participants per group, funded by Eli Lilly; the first two phase 3 trials (TRIUMPH-1 and TRIUMPH-2) were published in peer-reviewed journals on 29 September 2026; TRIUMPH-3 and TRIUMPH-4 had only been announced in press releases as of the review date. The drug is not approved in any country.", "sources": [ { "title": "Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526", "url": "https://doi.org/10.1056/NEJMoa2301972", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 37366315 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/37366315/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "Retatrutida fase 2 (obesidad)", "pageUrl": "https://saciedad.com/estudios/retatrutide-phase-2-obesity/", "pageUrlEn": "https://saciedad.com/en/studies/retatrutide-phase-2-obesity/" }, { "id": "select", "acronym": "SELECT", "title": "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes", "titleEn": "SELECT: semaglutide (Wegovy) and heart attacks and strokes", "firstAuthor": "Lincoff AM", "journal": "New England Journal of Medicine", "year": 2023, "doi": "10.1056/NEJMoa2307563", "url": "https://doi.org/10.1056/NEJMoa2307563", "registryId": "NCT03574597", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "17 604 adultos de 45 años o más con enfermedad cardiovascular establecida e IMC de 27 o más, sin diabetes.", "populationEn": "17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or more, without diabetes.", "nParticipants": 17604, "durationWeeks": null, "primaryOutcomeEs": "Primer evento cardiovascular mayor (muerte cardiovascular, infarto no mortal o ictus no mortal), semaglutida 2,4 mg frente a placebo.", "primaryOutcomeEn": "First major cardiovascular event (cardiovascular death, nonfatal heart attack or nonfatal stroke), semaglutide 2.4 mg versus placebo.", "resultSummaryEs": "Con un seguimiento medio de 39,8 meses, el evento cardiovascular mayor ocurrió en el 6,5 % de los pacientes con semaglutida 2,4 mg semanal y en el 8,0 % con placebo (hazard ratio 0,80; IC 95 %: 0,72 a 0,90; p < 0,001). Es el primer ensayo que muestra una reducción de eventos cardiovasculares con un fármaco para la obesidad en personas sin diabetes. Los efectos adversos llevaron a suspender el tratamiento de forma permanente al 16,6 % de los pacientes con semaglutida, frente al 8,2 % con placebo. La exposición media al tratamiento fue de 34,2 meses.", "resultSummaryEn": "With a mean follow-up of 39.8 months, a major cardiovascular event occurred in 6.5% of patients on semaglutide 2.4 mg once weekly and in 8.0% on placebo (hazard ratio 0.80; 95% CI, 0.72 to 0.90; p < 0.001). It is the first trial to show a reduction in cardiovascular events with an obesity drug in people without diabetes. Adverse effects led 16.6% of patients on semaglutide to stop treatment permanently, compared with 8.2% on placebo. Mean exposure to treatment was 34.2 months.", "limitationsEs": "Financiado por Novo Nordisk. Población con enfermedad cardiovascular previa, por lo que el beneficio absoluto no es extrapolable a personas con obesidad sin ese riesgo. El cambio de peso no forma parte del resumen del artículo y se detalla en el texto completo.", "limitationsEn": "Funded by Novo Nordisk. The population had prior cardiovascular disease, so the absolute benefit cannot be extrapolated to people with obesity who do not have that risk. The change in weight is not part of the paper’s abstract and is detailed in the full text.", "sources": [ { "title": "Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232", "url": "https://doi.org/10.1056/NEJMoa2307563", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 37952131 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/37952131/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SELECT", "pageUrl": "https://saciedad.com/estudios/select/", "pageUrlEn": "https://saciedad.com/en/studies/select/" }, { "id": "step-hfpef", "acronym": "STEP-HFpEF", "title": "Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity", "titleEn": "STEP-HFpEF: semaglutide 2.4 mg for heart failure with obesity", "firstAuthor": "Kosiborod MN", "journal": "New England Journal of Medicine", "year": 2023, "doi": "10.1056/NEJMoa2306963", "url": "https://doi.org/10.1056/NEJMoa2306963", "registryId": "NCT04788511", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "529 adultos con insuficiencia cardiaca con fracción de eyección preservada (fracción de eyección del ventrículo izquierdo del 45 % o más y síntomas de clase II a IV de la NYHA) e IMC de 30 o más, sin diabetes (HbA1c inferior al 6,5 %), aleatorizados a semaglutida 2,4 mg semanal (263) o placebo (266); edad media de 68 años y 297 mujeres.", "populationEn": "529 adults with heart failure with preserved ejection fraction (left ventricular ejection fraction of 45% or more and NYHA class II to IV symptoms) and a BMI of 30 or more, without diabetes (HbA1c below 6.5%), randomized to semaglutide 2.4 mg once weekly (263) or placebo (266); mean age 68 years and 297 women.", "nParticipants": 529, "durationWeeks": 52, "primaryOutcomeEs": "Dos objetivos principales a las 52 semanas: el cambio en la puntuación clínica resumida del cuestionario de miocardiopatía de Kansas City (KCCQ-CSS, de 0 a 100, en la que más puntos indican menos síntomas y limitaciones físicas) y el cambio porcentual del peso corporal.", "primaryOutcomeEn": "Two primary objectives at 52 weeks: the change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, from 0 to 100, where more points mean fewer symptoms and physical limitations) and the percentage change in body weight.", "resultSummaryEs": "A las 52 semanas, la puntuación KCCQ-CSS mejoró 16,6 puntos con semaglutida y 8,7 con placebo (diferencia de 7,8 puntos; IC 95 %: 4,8 a 10,9), y el peso cambió un −13,3 % frente a un −2,6 % (diferencia de −10,7 puntos porcentuales; IC 95 %: −11,9 a −9,4). La distancia recorrida en la prueba de marcha de 6 minutos aumentó 21,5 m con semaglutida y 1,2 m con placebo (diferencia de 20,3 m; IC 95 %: 8,6 a 32,1). La proteína C reactiva, un marcador de inflamación, bajó un 43,5 % con semaglutida y un 7,3 % con placebo. Hubo efectos adversos graves en el 13,3 % con semaglutida y en el 26,7 % con placebo.", "resultSummaryEn": "At 52 weeks, the KCCQ-CSS score improved by 16.6 points with semaglutide and 8.7 with placebo (difference of 7.8 points; 95% CI, 4.8 to 10.9), and weight changed by −13.3% versus −2.6% (difference of −10.7 percentage points; 95% CI, −11.9 to −9.4). The distance covered in the 6-minute walk test increased by 21.5 m with semaglutide and 1.2 m with placebo (difference of 20.3 m; 95% CI, 8.6 to 32.1). C-reactive protein, a marker of inflammation, fell by 43.5% with semaglutide and 7.3% with placebo. Serious adverse events occurred in 13.3% on semaglutide and 26.7% on placebo.", "limitationsEs": "Financiado por Novo Nordisk. Duró 52 semanas y, con 529 participantes, no permite sacar conclusiones sobre muertes ni hospitalizaciones por insuficiencia cardiaca. La mejora de síntomas se mide con un cuestionario que responden los propios participantes. Excluyó a personas con diabetes. Según el registro del ensayo, los resultados usan los datos de todos los aleatorizados mientras siguieron en el ensayo, hubieran dejado o no el tratamiento.", "limitationsEn": "Funded by Novo Nordisk. It lasted 52 weeks and, with 529 participants, it does not allow conclusions about deaths or hospitalizations for heart failure. The improvement in symptoms is measured with a questionnaire that participants fill in themselves. People with diabetes were excluded. According to the trial registry, the results use the data of everyone randomized for as long as they stayed in the trial, whether or not they had stopped treatment.", "sources": [ { "title": "Kosiborod MN, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023;389(12):1069-1084", "url": "https://doi.org/10.1056/NEJMoa2306963", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 37622681 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/37622681/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "ClinicalTrials.gov record NCT04788511 (eligibility, arm sizes, baseline and analysis period)", "url": "https://clinicaltrials.gov/study/NCT04788511", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP-HFpEF", "pageUrl": "https://saciedad.com/estudios/step-hfpef/", "pageUrlEn": "https://saciedad.com/en/studies/step-hfpef/" }, { "id": "surmount-2", "acronym": "SURMOUNT-2", "title": "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial", "titleEn": "SURMOUNT-2: tirzepatide (Zepbound) in type 2 diabetes", "firstAuthor": "Garvey WT", "journal": "The Lancet", "year": 2023, "doi": "10.1016/S0140-6736(23)01200-X", "url": "https://doi.org/10.1016/S0140-6736(23)01200-X", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "938 adultos con obesidad (IMC de 27 o más) y diabetes tipo 2; peso medio inicial de 100,7 kg y HbA1c del 8,02 %. El 60 % de los participantes eran hispanos o latinos.", "populationEn": "938 adults with obesity (BMI of 27 or more) and type 2 diabetes; mean starting weight of 100.7 kg and HbA1c of 8.02%. Of the participants, 60% were Hispanic or Latino.", "nParticipants": 938, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción con pérdida de al menos el 5 % a las 72 semanas, tirzepatida 10 y 15 mg frente a placebo.", "primaryOutcomeEn": "Percentage change in body weight and proportion losing at least 5% at 72 weeks, tirzepatide 10 and 15 mg versus placebo.", "resultSummaryEs": "En personas con diabetes tipo 2 y obesidad, tirzepatida redujo el peso un 12,8 % con 10 mg y un 14,7 % con 15 mg a las 72 semanas, frente al 3,2 % con placebo. Las diferencias estimadas fueron de −9,6 puntos porcentuales (IC 95 %: −11,1 a −8,1) y de −11,6 puntos (IC 95 %: −13,0 a −10,1). Entre el 79 % y el 83 % de los tratados perdió al menos el 5 % del peso, frente al 32 % con placebo. Los efectos adversos más frecuentes fueron náuseas, diarrea y vómitos, en su mayoría leves o moderados, con menos del 5 % de abandonos por esa causa.", "resultSummaryEn": "In people with type 2 diabetes and obesity, tirzepatide reduced weight by 12.8% with 10 mg and 14.7% with 15 mg at 72 weeks, compared with 3.2% on placebo. The estimated differences were −9.6 percentage points (95% CI, −11.1 to −8.1) and −11.6 points (95% CI, −13.0 to −10.1). Between 79% and 83% of treated participants lost at least 5% of their weight, compared with 32% on placebo. The most common adverse effects were nausea, diarrhea and vomiting, mostly mild or moderate, with fewer than 5% stopping treatment because of them.", "limitationsEs": "Financiado por Eli Lilly. La pérdida de peso fue menor que en SURMOUNT-1, como suele ocurrir en personas con diabetes tipo 2. Sin comparador activo.", "limitationsEn": "Funded by Eli Lilly. Weight loss was smaller than in SURMOUNT-1, as usually happens in people with type 2 diabetes. No active comparator.", "sources": [ { "title": "Garvey WT, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2). Lancet. 2023;402(10402):613-626", "url": "https://doi.org/10.1016/S0140-6736(23)01200-X", "publisher": "The Lancet", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 37385275 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/37385275/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-2", "pageUrl": "https://saciedad.com/estudios/surmount-2/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-2/" }, { "id": "surmount-3", "acronym": "SURMOUNT-3", "title": "Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial", "titleEn": "SURMOUNT-3: tirzepatide (Zepbound) after a lifestyle program", "firstAuthor": "Wadden TA", "journal": "Nature Medicine", "year": 2023, "doi": "10.1038/s41591-023-02597-w", "url": "https://doi.org/10.1038/s41591-023-02597-w", "registryId": "NCT04657016", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "806 adultos con IMC de 30 o más (o de 27 o más con al menos una complicación relacionada con la obesidad), sin diabetes, empezaron 12 semanas de intervención intensiva sobre el estilo de vida. Los 579 que perdieron al menos un 5,0 % del peso (un 6,9 % de media, de 109,5 a 101,9 kg) fueron aleatorizados a tirzepatida, 287, o a placebo, 292; 62,9 % mujeres y edad media de 45,6 años.", "populationEn": "806 adults with a BMI of 30 or more (or 27 or more with at least one obesity-related complication), without diabetes, started a 12-week intensive lifestyle intervention. The 579 who lost at least 5.0% of their weight (6.9% on average, from 109.5 to 101.9 kg) were randomized to tirzepatide, 287, or to placebo, 292; 62.9% women and mean age 45.6 years.", "nParticipants": 579, "durationWeeks": 72, "primaryOutcomeEs": "Dos objetivos coprincipales desde la aleatorización hasta la semana 72: cambio porcentual adicional del peso y proporción de participantes que perdieron al menos un 5 % adicional, con la dosis máxima tolerada de tirzepatida (10 o 15 mg semanales) frente a placebo.", "primaryOutcomeEn": "Two co-primary objectives from randomization to week 72: additional percentage change in weight and proportion of participants who lost at least an additional 5%, with the maximum tolerated dose of tirzepatide (10 or 15 mg once weekly) versus placebo.", "resultSummaryEs": "Desde la aleatorización hasta la semana 72, el peso cambió un −18,4 % adicional con tirzepatida y un +2,5 % con placebo; la diferencia estimada fue de −20,8 puntos porcentuales (IC 95 %: −23,2 a −18,5). El 87,5 % con tirzepatida perdió al menos un 5 % adicional, frente al 16,5 % con placebo (OR 34,6; IC 95 %: 19,2 a 62,6). Son resultados del estimando de régimen de tratamiento, que incluye a todos los aleatorizados sigan o no el tratamiento; con el estimando de eficacia, que supone que todos lo siguieron, la diferencia fue de −24,5 puntos porcentuales (IC 95 %: −26,1 a −22,8). Los efectos adversos más frecuentes con tirzepatida fueron digestivos, en su mayoría leves o moderados; el 10,5 % dejó el tratamiento por efectos adversos, frente al 2,1 % con placebo.", "resultSummaryEn": "From randomization to week 72, weight changed by an additional −18.4% with tirzepatide and +2.5% with placebo; the estimated difference was −20.8 percentage points (95% CI, −23.2 to −18.5). Of those on tirzepatide, 87.5% lost at least an additional 5%, compared with 16.5% on placebo (OR 34.6; 95% CI, 19.2 to 62.6). These are results for the treatment-regimen estimand, which includes everyone randomized whether or not they stayed on treatment; with the efficacy estimand, which assumes everyone stayed on it, the difference was −24.5 percentage points (95% CI, −26.1 to −22.8). The most common adverse effects with tirzepatide were digestive, mostly mild or moderate; 10.5% stopped treatment because of adverse effects, compared with 2.1% on placebo.", "limitationsEs": "Financiado por Eli Lilly, que contribuyó al diseño, supervisó la realización del estudio y apoyó la redacción. Solo incluyó a quienes ya habían perdido al menos un 5,0 % del peso en la fase inicial de 12 semanas, un grupo seleccionado. Excluyó a personas con diabetes, y la mayoría de los participantes eran blancos (86,0 %). Completaron el estudio más participantes con tirzepatida que con placebo (87,8 % frente a 77,7 %).", "limitationsEn": "Funded by Eli Lilly, which contributed to the design, oversaw the conduct of the study and supported the writing. It only included people who had already lost at least 5.0% of their weight in the initial 12-week phase, a selected group. People with diabetes were excluded, and most participants were white (86.0%). More participants completed the study on tirzepatide than on placebo (87.8% versus 77.7%).", "sources": [ { "title": "Wadden TA, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918", "url": "https://doi.org/10.1038/s41591-023-02597-w", "publisher": "Nature Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 37840095 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/37840095/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC10667099 (lead-in, efficacy estimand, discontinuations and funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-3", "pageUrl": "https://saciedad.com/estudios/surmount-3/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-3/" }, { "id": "flow", "acronym": "FLOW", "title": "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes", "titleEn": "FLOW: semaglutide (Ozempic) and kidney disease in type 2 diabetes", "firstAuthor": "Perkovic V", "journal": "New England Journal of Medicine", "year": 2024, "doi": "10.1056/NEJMoa2403347", "url": "https://doi.org/10.1056/NEJMoa2403347", "registryId": "NCT03819153", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "3533 pacientes con diabetes tipo 2 y enfermedad renal crónica (filtrado glomerular estimado de 50 a 75 ml/min/1,73 m² con un cociente albúmina/creatinina en orina de más de 300 y menos de 5000 mg/g, o filtrado de 25 a menos de 50 con un cociente de más de 100 y menos de 5000), aleatorizados a semaglutida 1,0 mg semanal (1767) o placebo (1766).", "populationEn": "3,533 patients with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate of 50 to 75 mL/min/1.73 m² with a urine albumin-to-creatinine ratio above 300 and below 5,000 mg/g, or a filtration rate of 25 to below 50 with a ratio above 100 and below 5,000), randomized to semaglutide 1.0 mg once weekly (1,767) or placebo (1,766).", "nParticipants": 3533, "durationWeeks": null, "primaryOutcomeEs": "Eventos renales mayores: compuesto de inicio de insuficiencia renal (diálisis, trasplante o filtrado glomerular estimado inferior a 15 ml/min/1,73 m²), reducción de al menos un 50 % del filtrado respecto al inicial o muerte de causa renal o cardiovascular, con semaglutida 1,0 mg semanal frente a placebo.", "primaryOutcomeEn": "Major kidney disease events: a composite of the onset of kidney failure (dialysis, transplantation or an estimated glomerular filtration rate below 15 mL/min/1.73 m²), a reduction of at least 50% in filtration rate from baseline, or death from kidney-related or cardiovascular causes, with semaglutide 1.0 mg once weekly versus placebo.", "resultSummaryEs": "Con una mediana de seguimiento de 3,4 años, el objetivo principal ocurrió en 331 pacientes con semaglutida y 410 con placebo, un riesgo un 24 % menor (hazard ratio 0,76; IC 95 %: 0,66 a 0,88). El ensayo terminó antes de lo previsto, tras recomendarse su interrupción en un análisis intermedio preespecificado. Los resultados fueron similares para el compuesto de los componentes renales (hazard ratio 0,79; IC 95 %: 0,66 a 0,94) y para la muerte cardiovascular (hazard ratio 0,71; IC 95 %: 0,56 a 0,89). El filtrado glomerular bajó cada año 1,16 ml/min/1,73 m² menos con semaglutida, el riesgo de eventos cardiovasculares mayores fue un 18 % menor (hazard ratio 0,82; IC 95 %: 0,68 a 0,98) y el de muerte por cualquier causa, un 20 % menor (hazard ratio 0,80; IC 95 %: 0,67 a 0,95). Hubo efectos adversos graves en el 49,6 % con semaglutida y en el 53,8 % con placebo.", "resultSummaryEn": "Over a median follow-up of 3.4 years, the primary outcome occurred in 331 patients on semaglutide and 410 on placebo, a 24% lower risk (hazard ratio 0.76; 95% CI, 0.66 to 0.88). The trial ended earlier than planned, after stopping was recommended at a prespecified interim analysis. Results were similar for the composite of the kidney-specific components (hazard ratio 0.79; 95% CI, 0.66 to 0.94) and for cardiovascular death (hazard ratio 0.71; 95% CI, 0.56 to 0.89). Glomerular filtration rate fell by 1.16 mL/min/1.73 m² less per year with semaglutide, the risk of major cardiovascular events was 18% lower (hazard ratio 0.82; 95% CI, 0.68 to 0.98) and the risk of death from any cause 20% lower (hazard ratio 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 49.6% on semaglutide and 53.8% on placebo.", "limitationsEs": "Financiado por Novo Nordisk. Terminó antes de lo previsto tras un análisis intermedio, y los ensayos que se detienen pronto pueden sobrestimar el tamaño del efecto. Usó semaglutida 1,0 mg, una dosis para la diabetes, no la de 2,4 mg que se usa para la obesidad. Solo incluyó a personas con diabetes tipo 2 y enfermedad renal crónica con albúmina en la orina, así que no se puede trasladar sin más a la enfermedad renal sin diabetes.", "limitationsEn": "Funded by Novo Nordisk. It ended earlier than planned after an interim analysis, and trials that stop early can overestimate the size of the effect. It used semaglutide 1.0 mg, a diabetes dose, not the 2.4 mg dose used for obesity. It only included people with type 2 diabetes and chronic kidney disease with albumin in the urine, so it cannot simply be applied to kidney disease without diabetes.", "sources": [ { "title": "Perkovic V, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121", "url": "https://doi.org/10.1056/NEJMoa2403347", "publisher": "New England Journal of Medicine", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 38785209 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/38785209/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT03819153 (registration and primary outcome)", "url": "https://clinicaltrials.gov/study/NCT03819153", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "FLOW", "pageUrl": "https://saciedad.com/estudios/flow/", "pageUrlEn": "https://saciedad.com/en/studies/flow/" }, { "id": "s-lite-seguimiento-sin-tratamiento", "acronym": "S-LiTE (seguimiento sin tratamiento)", "acronymEn": "S-LiTE (off-treatment follow-up)", "title": "Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial", "titleEn": "S-LiTE: exercise, liraglutide or both, a year after stopping", "firstAuthor": "Jensen SBK", "journal": "eClinicalMedicine", "year": 2024, "doi": "10.1016/j.eclinm.2024.102475", "url": "https://doi.org/10.1016/j.eclinm.2024.102475", "registryId": "NCT04122716", "drugIds": [ "liraglutida" ], "design": "rct", "populationEs": "Adultos con obesidad (18 a 65 años, IMC inicial de 32 a 43) que perdieron 13,1 kg de media con 8 semanas de dieta baja en calorías y fueron aleatorizados a un año de mantenimiento con ejercicio supervisado, liraglutida 3,0 mg, ambos o placebo; 109 acudieron a la evaluación un año después de terminar el tratamiento, en Copenhague.", "populationEn": "Adults with obesity (aged 18 to 65, baseline BMI of 32 to 43) who lost an average of 13.1 kg on an 8-week low-calorie diet and were randomized to one year of maintenance with supervised exercise, liraglutide 3.0 mg, both or placebo; 109 attended the assessment one year after treatment ended, in Copenhagen.", "nParticipants": 109, "durationWeeks": 104, "primaryOutcomeEs": "Cambio del peso corporal desde la aleatorización (semana 0) hasta un año después de terminar el tratamiento (semana 104), en la población por intención de tratar.", "primaryOutcomeEn": "Change in body weight from randomization (week 0) to one year after treatment ended (week 104), in the intention-to-treat population.", "resultSummaryEs": "Un año después de terminar el tratamiento, quienes habían recibido ejercicio más liraglutida pesaban 5,1 kg menos (IC 95 %: −10,0 a −0,2) y tenían un porcentaje de grasa 2,3 puntos menor (IC 95 %: −4,3 a −0,3) que quienes habían recibido solo liraglutida. Durante el año sin tratamiento, la recuperación de peso fue 6,0 kg mayor (IC 95 %: 2,1 a 10,0) tras dejar la liraglutida sola que tras dejar el ejercicio supervisado. Mantener una pérdida de al menos el 10 % del peso inicial fue más probable con la combinación que con placebo (OR 7,2; IC 95 %: 2,4 a 21,3) o que con liraglutida sola (OR 4,2; IC 95 %: 1,6 a 10,8), y con el ejercicio que con placebo (OR 3,7; IC 95 %: 1,2 a 11,1).", "resultSummaryEn": "One year after treatment ended, those who had received exercise plus liraglutide weighed 5.1 kg less (95% CI, −10.0 to −0.2) and had a body fat percentage 2.3 points lower (95% CI, −4.3 to −0.3) than those who had received liraglutide alone. During the year off treatment, weight regain was 6.0 kg greater (95% CI, 2.1 to 10.0) after stopping liraglutide alone than after stopping supervised exercise. Keeping off at least 10% of initial weight was more likely with the combination than with placebo (OR 7.2; 95% CI, 2.4 to 21.3) or with liraglutide alone (OR 4.2; 95% CI, 1.6 to 10.8), and with exercise than with placebo (OR 3.7; 95% CI, 1.2 to 11.1).", "limitationsEs": "Análisis posterior al tratamiento de un ensayo aleatorizado, con pérdida de seguimiento (109 de los participantes aleatorizados acudieron). Muestra pequeña. Usó liraglutida, no semaglutida ni tirzepatida, tras una pérdida inicial con dieta. Financiado por Helsefonden y la Novo Nordisk Foundation.", "limitationsEn": "A post-treatment analysis of a randomized trial, with loss to follow-up (109 of the randomized participants attended). Small sample. It used liraglutide, not semaglutide or tirzepatide, after an initial diet-induced loss. Funded by Helsefonden and the Novo Nordisk Foundation.", "sources": [ { "title": "Jensen SBK, et al. Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment. eClinicalMedicine. 2024;69:102475", "url": "https://doi.org/10.1016/j.eclinm.2024.102475", "publisher": "eClinicalMedicine (The Lancet)", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 38544798 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/38544798/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "S-LiTE (seguimiento sin tratamiento)", "pageUrl": "https://saciedad.com/estudios/s-lite-seguimiento-sin-tratamiento/", "pageUrlEn": "https://saciedad.com/en/studies/s-lite-seguimiento-sin-tratamiento/" }, { "id": "surmount-4", "acronym": "SURMOUNT-4", "title": "Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial", "titleEn": "SURMOUNT-4: what happens after stopping tirzepatide (Zepbound)", "firstAuthor": "Aronne LJ", "journal": "JAMA", "year": 2024, "doi": "10.1001/jama.2023.24945", "url": "https://doi.org/10.1001/jama.2023.24945", "registryId": "NCT04660643", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "783 adultos con IMC de 30 o más (o de 27 o más con al menos una complicación relacionada con el peso), sin diabetes, en 70 centros de 4 países; 670 fueron aleatorizados tras 36 semanas de tratamiento abierto (edad media de 48 años, 71 % mujeres, peso medio de 107,3 kg).", "populationEn": "783 adults with a BMI of 30 or more (or 27 or more with at least one weight-related complication), without diabetes, at 70 sites in 4 countries; 670 were randomized after 36 weeks of open-label treatment (mean age 48 years, 71% women, mean weight 107.3 kg).", "nParticipants": 670, "durationWeeks": 88, "primaryOutcomeEs": "Cambio porcentual medio del peso desde la semana 36 (aleatorización) hasta la semana 88, continuar con tirzepatida frente a cambiar a placebo.", "primaryOutcomeEn": "Mean percentage change in weight from week 36 (randomization) to week 88, continuing tirzepatide versus switching to placebo.", "resultSummaryEs": "De la semana 36 a la 88, el peso cambió un −5,5 % en quienes siguieron con tirzepatida y un +14,0 % en quienes pasaron a placebo (diferencia de −19,4 puntos porcentuales; IC 95 %: −21,2 a −17,7). Antes de la aleatorización, en las 36 semanas iniciales con la dosis máxima tolerada de tirzepatida (10 o 15 mg), habían perdido de media un 20,9 % del peso. El 89,5 % de quienes continuaron mantuvo al menos el 80 % del peso perdido, frente al 16,6 % con placebo. Desde la semana 0 a la 88, la reducción media fue del 25,3 % con tirzepatida y del 9,9 % con placebo. Los efectos adversos más frecuentes fueron digestivos, en su mayoría leves o moderados, y más habituales con tirzepatida.", "resultSummaryEn": "From week 36 to week 88, weight changed by −5.5% in those who stayed on tirzepatide and by +14.0% in those switched to placebo (difference of −19.4 percentage points; 95% CI, −21.2 to −17.7). Before randomization, during the first 36 weeks on the maximum tolerated dose of tirzepatide (10 or 15 mg), they had lost an average of 20.9% of their weight. Of those who continued, 89.5% kept off at least 80% of the weight they had lost, compared with 16.6% on placebo. From week 0 to week 88, the mean reduction was 25.3% with tirzepatide and 9.9% with placebo. The most common adverse effects were digestive, mostly mild or moderate, and more frequent with tirzepatide.", "limitationsEs": "Financiado por Eli Lilly, que participó en el diseño, el análisis y la redacción. El periodo inicial abierto de 36 semanas seleccionó a quienes toleraron el fármaco. Excluyó a personas con diabetes. Refleja una retirada completa a placebo, no una reducción progresiva de la dosis ni un cambio a otro tratamiento, y no evaluó estrategias nutricionales específicas tras la retirada.", "limitationsEn": "Funded by Eli Lilly, which took part in the design, analysis and writing. The initial 36-week open-label period selected people who tolerated the drug. People with diabetes were excluded. It reflects complete withdrawal to placebo, not a gradual dose reduction or a switch to another treatment, and it did not evaluate specific nutrition strategies after withdrawal.", "sources": [ { "title": "Aronne LJ, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38-48", "url": "https://doi.org/10.1001/jama.2023.24945", "publisher": "JAMA", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 38078870 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/38078870/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC10714284 (funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10714284/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-4", "pageUrl": "https://saciedad.com/estudios/surmount-4/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-4/" }, { "id": "surmount-osa", "acronym": "SURMOUNT-OSA", "title": "Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity", "titleEn": "SURMOUNT-OSA: tirzepatide (Zepbound) for sleep apnea and obesity", "firstAuthor": "Malhotra A", "journal": "New England Journal of Medicine", "year": 2024, "doi": "10.1056/NEJMoa2404881", "url": "https://doi.org/10.1056/NEJMoa2404881", "registryId": "NCT05412004", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "469 adultos con apnea obstructiva del sueño moderada o grave y obesidad (IMC de 30 o más; 27 o más en Japón), sin diabetes, en dos ensayos paralelos: el ensayo 1 con 234 personas que no usaban presión positiva en la vía respiratoria (PAP, como la CPAP) y el ensayo 2 con 235 que sí la usaban. El índice de apnea-hipopnea medio inicial era de 51,5 y 49,5 eventos por hora, y el IMC medio de 39,1 y 38,7.", "populationEn": "469 adults with moderate or severe obstructive sleep apnea and obesity (BMI of 30 or more; 27 or more in Japan), without diabetes, in two parallel trials: trial 1 with 234 people who were not using positive airway pressure (PAP, such as CPAP) and trial 2 with 235 who were. Mean baseline apnea-hypopnea index was 51.5 and 49.5 events per hour, and mean BMI was 39.1 and 38.7.", "nParticipants": 469, "durationWeeks": 52, "primaryOutcomeEs": "Cambio del índice de apnea-hipopnea (IAH, número de apneas e hipopneas por hora de sueño) desde el inicio hasta la semana 52 con la dosis máxima tolerada de tirzepatida (10 o 15 mg semanales) frente a placebo.", "primaryOutcomeEn": "Change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas per hour of sleep) from baseline to week 52 with the maximum tolerated dose of tirzepatide (10 or 15 mg once weekly) versus placebo.", "resultSummaryEs": "A las 52 semanas, el IAH bajó 25,3 eventos por hora con tirzepatida y 5,3 con placebo en el ensayo 1 (diferencia de −20,0; IC 95 %: −25,8 a −14,2), y 29,3 frente a 5,5 en el ensayo 2 (diferencia de −23,8; IC 95 %: −29,6 a −17,9). El peso cambió un −17,7 % frente a un −1,6 % en el ensayo 1 (diferencia de −16,1 puntos porcentuales; IC 95 %: −18,0 a −14,2) y un −19,6 % frente a un −2,3 % en el ensayo 2 (diferencia de −17,3 puntos; IC 95 %: −19,3 a −15,3). También mejoraron frente a placebo la carga hipóxica, la proteína C reactiva, la presión arterial sistólica y las alteraciones del sueño comunicadas por los participantes. Los efectos adversos más frecuentes con tirzepatida fueron digestivos, en su mayoría leves o moderados.", "resultSummaryEn": "At 52 weeks, the AHI fell by 25.3 events per hour with tirzepatide and 5.3 with placebo in trial 1 (difference of −20.0; 95% CI, −25.8 to −14.2), and by 29.3 versus 5.5 in trial 2 (difference of −23.8; 95% CI, −29.6 to −17.9). Weight changed by −17.7% versus −1.6% in trial 1 (difference of −16.1 percentage points; 95% CI, −18.0 to −14.2) and by −19.6% versus −2.3% in trial 2 (difference of −17.3 points; 95% CI, −19.3 to −15.3). Hypoxic burden, C-reactive protein, systolic blood pressure and participant-reported sleep impairment also improved versus placebo. The most common adverse effects with tirzepatide were digestive, mostly mild or moderate.", "limitationsEs": "Financiado por Eli Lilly; los análisis estadísticos los hicieron empleados del promotor. Con 52 semanas no permite evaluar resultados cardiovasculares a largo plazo. Solo incluyó a personas con obesidad y sin diabetes. El ensayo 2 no se diseñó para saber si el fármaco cambia el uso de la CPAP. Completó el ensayo el 91,5 % de los participantes con tirzepatida y el 74,4 % con placebo.", "limitationsEn": "Funded by Eli Lilly; the statistical analyses were done by employees of the sponsor. At 52 weeks, it cannot assess long-term cardiovascular outcomes. It only included people with obesity and without diabetes. Trial 2 was not designed to find out whether the drug changes CPAP use. The trial was completed by 91.5% of participants on tirzepatide and 74.4% on placebo.", "sources": [ { "title": "Malhotra A, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024;391(13):1193-1205", "url": "https://doi.org/10.1056/NEJMoa2404881", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 38912654 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/38912654/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC11598664 (author manuscript: participants, weight results, limitations, funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11598664/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-OSA", "pageUrl": "https://saciedad.com/estudios/surmount-osa/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-osa/" }, { "id": "achieve-1", "acronym": "ACHIEVE-1", "title": "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes", "titleEn": "ACHIEVE-1: the orforglipron pill in early type 2 diabetes", "firstAuthor": "Rosenstock J", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2505669", "url": "https://doi.org/10.1056/NEJMoa2505669", "registryId": "NCT05971940", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "559 adultos con diabetes tipo 2 de inicio reciente tratada solo con dieta y ejercicio; HbA1c inicial del 8,0 %.", "populationEn": "559 adults with recently diagnosed type 2 diabetes treated with diet and exercise alone; baseline HbA1c of 8.0%.", "nParticipants": 559, "durationWeeks": 40, "primaryOutcomeEs": "Cambio de la HbA1c a las 40 semanas con orforglipron 3, 12 o 36 mg diarios frente a placebo.", "primaryOutcomeEn": "Change in HbA1c at 40 weeks with orforglipron 3, 12 or 36 mg daily versus placebo.", "resultSummaryEs": "La HbA1c bajó 1,24, 1,47 y 1,48 puntos porcentuales con orforglipron 3, 12 y 36 mg, frente a 0,41 puntos con placebo; las diferencias fueron de −0,83 (IC 95 %: −1,10 a −0,56), −1,06 (IC 95 %: −1,33 a −0,79) y −1,07 puntos (IC 95 %: −1,33 a −0,81). El peso se redujo un 4,5 %, un 5,8 % y un 7,6 %, frente al 1,7 % con placebo. Los efectos adversos más frecuentes fueron digestivos, de intensidad leve a moderada.", "resultSummaryEn": "HbA1c fell by 1.24, 1.47 and 1.48 percentage points with orforglipron 3, 12 and 36 mg, compared with 0.41 points on placebo; the differences were −0.83 (95% CI, −1.10 to −0.56), −1.06 (95% CI, −1.33 to −0.79) and −1.07 points (95% CI, −1.33 to −0.81). Weight fell by 4.5%, 5.8% and 7.6%, compared with 1.7% on placebo. The most common adverse effects were digestive, mild to moderate in severity.", "limitationsEs": "Financiado por Eli Lilly. Población con diabetes reciente y sin otros antidiabéticos, por lo que no informa del uso combinado con metformina u otros fármacos. En la fecha de revisión, la indicación en diabetes tipo 2 estaba en evaluación por la FDA.", "limitationsEn": "Funded by Eli Lilly. The population had recent diabetes and took no other diabetes drugs, so it says nothing about use in combination with metformin or other drugs. As of the review date, the type 2 diabetes indication was under FDA review.", "sources": [ { "title": "Rosenstock J, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. N Engl J Med. 2025;393(11):1065-1076", "url": "https://doi.org/10.1056/NEJMoa2505669", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40544435 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40544435/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "ACHIEVE-1", "pageUrl": "https://saciedad.com/estudios/achieve-1/", "pageUrlEn": "https://saciedad.com/en/studies/achieve-1/" }, { "id": "attain-1", "acronym": "ATTAIN-1", "title": "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment", "titleEn": "ATTAIN-1: orforglipron, a daily GLP-1 pill, for obesity", "firstAuthor": "Wharton S", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2511774", "url": "https://doi.org/10.1056/NEJMoa2511774", "registryId": "NCT05869903", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "3127 adultos con obesidad (o sobrepeso con al menos una complicación relacionada con el peso), sin diabetes.", "populationEn": "3,127 adults with obesity (or overweight with at least one weight-related complication), without diabetes.", "nParticipants": 3127, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual del peso corporal a las 72 semanas con orforglipron oral 6, 12 o 36 mg diarios frente a placebo.", "primaryOutcomeEn": "Percentage change in body weight at 72 weeks with oral orforglipron 6, 12 or 36 mg daily versus placebo.", "resultSummaryEs": "Orforglipron, un agonista del receptor GLP-1 oral de molécula pequeña, redujo el peso a las 72 semanas un 11,2 % con 36 mg (IC 95 %: −12,0 a −10,4), un 8,4 % con 12 mg (IC 95 %: −9,1 a −7,7) y un 7,5 % con 6 mg (IC 95 %: −8,2 a −6,8), frente al 2,1 % con placebo (IC 95 %: −2,8 a −1,4). La diferencia frente a placebo con 36 mg fue de −9,1 puntos porcentuales (IC 95 %: −10,1 a −8,1). El fármaco se inició con 1 mg y se escaló cada 4 semanas hasta la dosis asignada. Los efectos adversos más frecuentes fueron digestivos.", "resultSummaryEn": "Orforglipron, an oral small-molecule GLP-1 receptor agonist, reduced weight at 72 weeks by 11.2% with 36 mg (95% CI, −12.0 to −10.4), 8.4% with 12 mg (95% CI, −9.1 to −7.7) and 7.5% with 6 mg (95% CI, −8.2 to −6.8), compared with 2.1% on placebo (95% CI, −2.8 to −1.4). The difference versus placebo with 36 mg was −9.1 percentage points (95% CI, −10.1 to −8.1). The drug was started at 1 mg and increased every 4 weeks up to the assigned dose. The most common adverse effects were digestive.", "limitationsEs": "Financiado por Eli Lilly. La pérdida de peso es menor que la de los inyectables semanales, aunque no se compararon directamente. Las dosis del ensayo (6, 12 y 36 mg) no coinciden con las etiquetas de dosis del producto aprobado en Estados Unidos en 2026 (Foundayo: 5,5, 9 y 17,2 mg), que la FDA hace equivaler a las del ensayo.", "limitationsEn": "Funded by Eli Lilly. Weight loss is smaller than with the weekly injectables, although they were not compared directly. The trial doses (6, 12 and 36 mg) do not match the dose strengths on the label of the product approved in the United States in 2026 (Foundayo: 5.5, 9 and 17.2 mg), which the FDA treats as equivalent to the trial doses.", "sources": [ { "title": "Wharton S, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med. 2025;393(18):1796-1806", "url": "https://doi.org/10.1056/NEJMoa2511774", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40960239 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40960239/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "ATTAIN-1", "pageUrl": "https://saciedad.com/estudios/attain-1/", "pageUrlEn": "https://saciedad.com/en/studies/attain-1/" }, { "id": "attain-2", "acronym": "ATTAIN-2", "title": "Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial", "titleEn": "ATTAIN-2: orforglipron, a daily pill, for obesity with diabetes", "firstAuthor": "Horn DB", "journal": "The Lancet", "year": 2025, "doi": "10.1016/S0140-6736(25)02165-8", "url": "https://doi.org/10.1016/S0140-6736(25)02165-8", "registryId": "NCT05872620", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "1613 adultos con diabetes tipo 2 (HbA1c del 7 al 10 %) e IMC de 27 o más, en 136 centros de diez países, aleatorizados a orforglipron 6 mg (329), 12 mg (332) o 36 mg (322) o a placebo (630); 46,9 % mujeres, peso medio de 101,4 kg, IMC medio de 35,6 y HbA1c media de 8,05 %.", "populationEn": "1,613 adults with type 2 diabetes (HbA1c of 7 to 10%) and a BMI of 27 or more, at 136 sites in ten countries, randomized to orforglipron 6 mg (329), 12 mg (332) or 36 mg (322) or to placebo (630); 46.9% women, mean weight 101.4 kg, mean BMI 35.6 and mean HbA1c 8.05%.", "nParticipants": 1613, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual medio del peso corporal desde el inicio hasta la semana 72 con orforglipron oral 6, 12 o 36 mg diarios frente a placebo, como complemento de cambios en el estilo de vida.", "primaryOutcomeEn": "Mean percentage change in body weight from baseline to week 72 with oral orforglipron 6, 12 or 36 mg daily versus placebo, as an adjunct to lifestyle changes.", "resultSummaryEs": "A las 72 semanas, el peso cambió un −9,6 % con orforglipron 36 mg, un −7,0 % con 12 mg y un −5,1 % con 6 mg, frente a un −2,5 % con placebo; la diferencia frente a placebo fue de −7,1 puntos porcentuales con 36 mg (IC 95 %: −8,2 a −6,1), de −4,5 con 12 mg (IC 95 %: −5,5 a −3,6) y de −2,7 con 6 mg (IC 95 %: −3,7 a −1,6). Son resultados del estimando de régimen de tratamiento, que incluye a todos los aleatorizados con independencia de lo que ocurriera durante el ensayo. La HbA1c y todas las medidas de peso y cardiometabólicas preespecificadas mejoraron con orforglipron. Los efectos adversos más frecuentes fueron digestivos, leves o moderados y sobre todo durante la escalada de dosis; dejaron el tratamiento por efectos adversos entre el 6,1 y el 9,9 % con orforglipron, frente al 4,1 % con placebo.", "resultSummaryEn": "At 72 weeks, weight changed by −9.6% with orforglipron 36 mg, −7.0% with 12 mg and −5.1% with 6 mg, compared with −2.5% on placebo; the difference versus placebo was −7.1 percentage points with 36 mg (95% CI, −8.2 to −6.1), −4.5 with 12 mg (95% CI, −5.5 to −3.6) and −2.7 with 6 mg (95% CI, −3.7 to −1.6). These are results for the treatment-regimen estimand, which includes everyone randomized regardless of what happened during the trial. HbA1c and all prespecified weight and cardiometabolic measures improved with orforglipron. The most common adverse effects were digestive, mild or moderate and mostly during dose escalation; between 6.1 and 9.9% stopped treatment because of adverse effects on orforglipron, compared with 4.1% on placebo.", "limitationsEs": "Financiado por Eli Lilly, que desarrolla el orforglipron. Incluyó solo a personas con diabetes tipo 2, en quienes la pérdida de peso con estos fármacos suele ser menor que sin diabetes, así que sus cifras no se comparan directamente con las de ATTAIN-1. Se comparó con placebo, no con otros tratamientos. Hubo 10 muertes (6 con orforglipron y 4 con placebo), que los investigadores no atribuyeron al fármaco.", "limitationsEn": "Funded by Eli Lilly, which is developing orforglipron. It included only people with type 2 diabetes, in whom weight loss with these drugs is usually smaller than in people without diabetes, so its figures are not directly comparable with those of ATTAIN-1. It was compared with placebo, not with other treatments. There were 10 deaths (6 on orforglipron and 4 on placebo), which the investigators did not attribute to the drug.", "sources": [ { "title": "Horn DB, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2025;406(10522):2927-2944", "url": "https://doi.org/10.1016/S0140-6736(25)02165-8", "publisher": "The Lancet", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 41275875 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/41275875/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "ATTAIN-2", "pageUrl": "https://saciedad.com/estudios/attain-2/", "pageUrlEn": "https://saciedad.com/en/studies/attain-2/" }, { "id": "essence", "acronym": "ESSENCE", "title": "Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis", "titleEn": "ESSENCE: semaglutide 2.4 mg (Wegovy) for MASH liver disease", "firstAuthor": "Sanyal AJ", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2413258", "url": "https://doi.org/10.1056/NEJMoa2413258", "registryId": "NCT04822181", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "1197 pacientes con esteatohepatitis asociada a disfunción metabólica (MASH) confirmada por biopsia y fibrosis hepática en estadio 2 o 3, aleatorizados en proporción 2:1 a semaglutida 2,4 mg semanal o placebo durante 240 semanas; esta publicación es el análisis intermedio previsto a las 72 semanas en los primeros 800 (534 con semaglutida y 266 con placebo).", "populationEn": "1,197 patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or 3 liver fibrosis, randomized 2:1 to semaglutide 2.4 mg once weekly or placebo for 240 weeks; this paper is the planned interim analysis at 72 weeks in the first 800 (534 on semaglutide and 266 on placebo).", "nParticipants": 800, "durationWeeks": 72, "primaryOutcomeEs": "Dos objetivos principales de la primera parte, evaluados en la biopsia hepática a las 72 semanas: resolución de la esteatohepatitis sin empeoramiento de la fibrosis, y reducción de la fibrosis sin empeoramiento de la esteatohepatitis.", "primaryOutcomeEn": "Two primary objectives of the first part, assessed on liver biopsy at 72 weeks: resolution of steatohepatitis without worsening of fibrosis, and reduction in fibrosis without worsening of steatohepatitis.", "resultSummaryEs": "A las 72 semanas, la esteatohepatitis se resolvió sin empeoramiento de la fibrosis en el 62,9 % con semaglutida y en el 34,3 % con placebo (diferencia de 28,7 puntos porcentuales; IC 95 %: 21,1 a 36,2), y la fibrosis se redujo sin empeoramiento de la esteatohepatitis en el 36,8 % frente al 22,4 % (diferencia de 14,4 puntos porcentuales; IC 95 %: 7,5 a 21,3). Las dos cosas a la vez ocurrieron en el 32,7 % frente al 16,1 % (diferencia de 16,5 puntos porcentuales; IC 95 %: 10,2 a 22,8). El peso cambió un −10,5 % con semaglutida y un −2,0 % con placebo (diferencia de −8,5 puntos porcentuales; IC 95 %: −9,6 a −7,4). Las puntuaciones de dolor corporal no difirieron entre los grupos, y los efectos adversos digestivos fueron más frecuentes con semaglutida.", "resultSummaryEn": "At 72 weeks, steatohepatitis resolved without worsening of fibrosis in 62.9% on semaglutide and 34.3% on placebo (difference of 28.7 percentage points; 95% CI, 21.1 to 36.2), and fibrosis was reduced without worsening of steatohepatitis in 36.8% versus 22.4% (difference of 14.4 percentage points; 95% CI, 7.5 to 21.3). Both happened together in 32.7% versus 16.1% (difference of 16.5 percentage points; 95% CI, 10.2 to 22.8). Weight changed by −10.5% with semaglutide and −2.0% with placebo (difference of −8.5 percentage points; 95% CI, −9.6 to −7.4). Bodily pain scores did not differ between the groups, and digestive adverse events were more common with semaglutide.", "limitationsEs": "Financiado por Novo Nordisk. Es un análisis intermedio de un ensayo que sigue en marcha: todavía no se sabe si la semaglutida reduce la cirrosis u otros eventos hepáticos, que según el registro son el objetivo de la segunda parte, a las 240 semanas. Los resultados se basan en cambios en la biopsia, un marcador intermedio, y no en síntomas ni eventos clínicos. Solo incluyó a personas con fibrosis moderada o avanzada (estadios 2 y 3), no con cirrosis.", "limitationsEn": "Funded by Novo Nordisk. It is an interim analysis of an ongoing trial: it is not yet known whether semaglutide reduces cirrhosis or other liver events, which according to the registry are the objective of the second part, at 240 weeks. The results are based on changes in the biopsy, an intermediate marker, not on symptoms or clinical events. It only included people with moderate or advanced fibrosis (stages 2 and 3), not with cirrhosis.", "sources": [ { "title": "Sanyal AJ, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089-2099", "url": "https://doi.org/10.1056/NEJMoa2413258", "publisher": "New England Journal of Medicine", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 40305708 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40305708/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT04822181 (part 1 and part 2 primary outcomes)", "url": "https://clinicaltrials.gov/study/NCT04822181", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "ESSENCE", "pageUrl": "https://saciedad.com/estudios/essence/", "pageUrlEn": "https://saciedad.com/en/studies/essence/" }, { "id": "oasis-2", "acronym": "OASIS 2", "title": "Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial", "titleEn": "OASIS 2: oral semaglutide 50 mg in East Asian adults", "firstAuthor": "Kadowaki T", "journal": "JAMA Internal Medicine", "year": 2025, "doi": "10.1001/jamainternmed.2025.3599", "url": "https://doi.org/10.1001/jamainternmed.2025.3599", "registryId": "NCT05132088", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "201 adultos de Japón y Corea del Sur con IMC de 27,0 o más y al menos dos complicaciones relacionadas con el peso, o de 35,0 o más y al menos una, el 25,4 % de ellos con diabetes tipo 2, aleatorizados en proporción 2:1 a semaglutida oral 50 mg diaria (134) o placebo (67); edad media de 49 años, peso medio de 91,9 kg y 43,3 % mujeres.", "populationEn": "201 adults in Japan and South Korea with a BMI of 27.0 or more and at least two weight-related complications, or 35.0 or more and at least one, 25.4% of them with type 2 diabetes, randomized 2:1 to oral semaglutide 50 mg daily (134) or placebo (67); mean age 49 years, mean weight 91.9 kg and 43.3% women.", "nParticipants": 201, "durationWeeks": 68, "primaryOutcomeEs": "Dos objetivos coprincipales a las 68 semanas: cambio porcentual del peso y proporción de participantes que redujeron al menos un 5 % el peso, con semaglutida oral 50 mg diaria frente a placebo, ambos con recomendaciones de estilo de vida.", "primaryOutcomeEn": "Two co-primary objectives at 68 weeks: percentage change in weight and proportion of participants who reduced their weight by at least 5%, with oral semaglutide 50 mg daily versus placebo, both with lifestyle recommendations.", "resultSummaryEs": "A las 68 semanas, el peso cambió un −14,3 % con semaglutida oral 50 mg y un −1,3 % con placebo; la diferencia estimada fue de −13,07 puntos porcentuales (IC 95 %: −15,61 a −10,52). Redujeron el peso al menos un 5 % 107 de 127 participantes con semaglutida (84,3 %) y 11 de 64 con placebo (17,2 %) (OR 23,00; IC 95 %: 10,28 a 51,42). Son resultados del estimando de política de tratamiento, que incluye a todos los aleatorizados con independencia de que dejaran el tratamiento o usaran otras terapias para perder peso. Los efectos adversos digestivos afectaron al 63,4 % con semaglutida y al 34,8 % con placebo, y el 4,5 % con semaglutida dejó el tratamiento por efectos adversos.", "resultSummaryEn": "At 68 weeks, weight changed by −14.3% with oral semaglutide 50 mg and −1.3% with placebo; the estimated difference was −13.07 percentage points (95% CI, −15.61 to −10.52). Weight fell by at least 5% in 107 of 127 participants on semaglutide (84.3%) and 11 of 64 on placebo (17.2%) (OR 23.00; 95% CI, 10.28 to 51.42). These are results for the treatment-policy estimand, which includes everyone randomized whether or not they stopped treatment or used other weight-loss therapies. Digestive adverse events affected 63.4% on semaglutide and 34.8% on placebo, and 4.5% on semaglutide stopped treatment because of adverse events.", "limitationsEs": "Financiado por Novo Nordisk, que participó en el diseño, el análisis de los datos y la redacción. Fue un ensayo pequeño, con 201 participantes, solo en Japón y Corea del Sur, así que sus resultados no se pueden trasladar sin más a otras poblaciones. Estudió una dosis diaria de 50 mg, que al final tomaba el 81,4 % de quienes completaron el tratamiento con semaglutida, y no se comparó con la semaglutida inyectable. En el subgrupo con diabetes tipo 2, de solo 51 personas, la pérdida de peso fue menor (−10,7 % con semaglutida frente a −1,5 % con placebo).", "limitationsEn": "Funded by Novo Nordisk, which took part in the design, the data analysis and the writing. It was a small trial, with 201 participants, only in Japan and South Korea, so its results cannot simply be applied to other populations. It studied a daily dose of 50 mg, which 81.4% of those who completed semaglutide treatment were taking at the end, and it was not compared with injectable semaglutide. In the subgroup with type 2 diabetes, of only 51 people, weight loss was smaller (−10.7% with semaglutide versus −1.5% with placebo).", "sources": [ { "title": "Kadowaki T, et al. Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial. JAMA Intern Med. 2025;185(10):1206-1217", "url": "https://doi.org/10.1001/jamainternmed.2025.3599", "publisher": "JAMA Internal Medicine", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 40758358 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40758358/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "Full text PMC12322823 (estimands, dose at week 68, type 2 diabetes subgroup and role of the funder)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12322823/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "OASIS 2", "pageUrl": "https://saciedad.com/estudios/oasis-2/", "pageUrlEn": "https://saciedad.com/en/studies/oasis-2/" }, { "id": "oasis-4", "acronym": "OASIS 4", "title": "Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity", "titleEn": "OASIS 4: oral semaglutide 25 mg (the Wegovy pill) for obesity", "firstAuthor": "Wharton S", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2500969", "url": "https://doi.org/10.1056/NEJMoa2500969", "registryId": "NCT05564117", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "307 adultos sin diabetes con obesidad (IMC de 30 o más) o con IMC de 27 o más y al menos una complicación relacionada con la obesidad, en 22 centros de cuatro países.", "populationEn": "307 adults without diabetes with obesity (BMI of 30 or more) or with a BMI of 27 or more and at least one obesity-related complication, at 22 sites in four countries.", "nParticipants": 307, "durationWeeks": 64, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción que redujo al menos un 5 % el peso a las 64 semanas con semaglutida oral 25 mg diaria frente a placebo, ambos con intervención sobre el estilo de vida.", "primaryOutcomeEn": "Percentage change in body weight and proportion reducing their weight by at least 5% at 64 weeks with oral semaglutide 25 mg daily versus placebo, both with a lifestyle intervention.", "resultSummaryEs": "El peso cambió un −13,6 % con semaglutida oral 25 mg y un −2,2 % con placebo a las 64 semanas; la diferencia estimada fue de −11,4 puntos porcentuales (IC 95 %: −13,9 a −9,0). Más participantes con semaglutida alcanzaron reducciones de al menos el 5, 10, 15 y 20 % y mejoraron la puntuación de función física del IWQOL-Lite-CT. Los efectos adversos digestivos fueron más frecuentes con semaglutida (74,0 % frente a 42,2 %).", "resultSummaryEn": "Weight changed by −13.6% with oral semaglutide 25 mg and −2.2% with placebo at 64 weeks; the estimated difference was −11.4 percentage points (95% CI, −13.9 to −9.0). More participants on semaglutide achieved reductions of at least 5, 10, 15 and 20% and improved their IWQOL-Lite-CT physical function score. Digestive adverse effects were more frequent with semaglutide (74.0% versus 42.2%).", "limitationsEs": "Financiado por Novo Nordisk. Muestra pequeña (205 participantes con semaglutida oral y 102 con placebo) y sin personas con diabetes. Se comparó con placebo, no con la semaglutida inyectable, así que no dice cuál de las dos formas reduce más el peso.", "limitationsEn": "Funded by Novo Nordisk. Small sample (205 participants on oral semaglutide and 102 on placebo) and no people with diabetes. It was compared with placebo, not with injectable semaglutide, so it does not say which of the two forms reduces weight more.", "sources": [ { "title": "Wharton S, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. N Engl J Med. 2025;393(11):1077-1087", "url": "https://doi.org/10.1056/NEJMoa2500969", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40934115 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40934115/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "OASIS 4", "pageUrl": "https://saciedad.com/estudios/oasis-4/", "pageUrlEn": "https://saciedad.com/en/studies/oasis-4/" }, { "id": "redefine-1", "acronym": "REDEFINE 1", "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity", "titleEn": "REDEFINE 1: CagriSema for obesity without diabetes", "firstAuthor": "Garvey WT", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2502081", "url": "https://doi.org/10.1056/NEJMoa2502081", "registryId": "NCT05567796", "drugIds": [ "cagrisema", "semaglutida" ], "design": "rct", "populationEs": "3417 adultos con obesidad (o sobrepeso con al menos una comorbilidad), sin diabetes, asignados a CagriSema, semaglutida sola, cagrilintida sola o placebo.", "populationEn": "3,417 adults with obesity (or overweight with at least one comorbidity), without diabetes, assigned to CagriSema, semaglutide alone, cagrilintide alone or placebo.", "nParticipants": 3417, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción con pérdida de al menos el 5 % a las 68 semanas, CagriSema frente a placebo.", "primaryOutcomeEn": "Percentage change in body weight and proportion losing at least 5% at 68 weeks, CagriSema versus placebo.", "resultSummaryEs": "CagriSema (cagrilintida 2,4 mg más semaglutida 2,4 mg, una vez por semana) redujo el peso un 20,4 % a las 68 semanas, frente al 3,0 % con placebo; la diferencia estimada fue de −17,3 puntos porcentuales (IC 95 %: −18,1 a −16,6; p < 0,001). Según la nota de prensa del promotor, los grupos de semaglutida sola y cagrilintida sola perdieron un 14,9 % y un 11,5 % con el mismo estimando; esas cifras no figuran en el resumen del artículo. Los efectos adversos más frecuentes fueron digestivos.", "resultSummaryEn": "CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg, once weekly) reduced weight by 20.4% at 68 weeks, compared with 3.0% on placebo; the estimated difference was −17.3 percentage points (95% CI, −18.1 to −16.6; p < 0.001). According to the sponsor’s press release, the semaglutide-alone and cagrilintide-alone groups lost 14.9% and 11.5% with the same estimand; those figures are not in the paper’s abstract. The most common adverse effects were digestive.", "limitationsEs": "Financiado por Novo Nordisk. Los intervalos de confianza de las comparaciones frente a semaglutida y cagrilintida solas no aparecen en el resumen publicado. Se permitió flexibilidad de dosis, lo que complica la interpretación. El producto no estaba aprobado en ningún país en la fecha de revisión.", "limitationsEn": "Funded by Novo Nordisk. The confidence intervals for the comparisons with semaglutide alone and cagrilintide alone are not in the published abstract. Flexible dosing was allowed, which complicates interpretation. The product was not approved in any country as of the review date.", "sources": [ { "title": "Garvey WT, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025;393(7):635-647", "url": "https://doi.org/10.1056/NEJMoa2502081", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40544433 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40544433/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Novo Nordisk press release: CagriSema demonstrates superior weight loss in adults with obesity or overweight in the REDEFINE 1 trial (20 December 2024)", "url": "https://www.globenewswire.com/news-release/2024/12/20/3000444/0/en/Novo-Nordisk-A-S-CagriSema-demonstrates-superior-weight-loss-in-adults-with-obesity-or-overweight-in-the-REDEFINE-1-trial.html", "publisher": "Novo Nordisk A/S (GlobeNewswire)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "REDEFINE 1", "pageUrl": "https://saciedad.com/estudios/redefine-1/", "pageUrlEn": "https://saciedad.com/en/studies/redefine-1/" }, { "id": "redefine-2", "acronym": "REDEFINE 2", "title": "Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes", "titleEn": "REDEFINE 2: CagriSema in type 2 diabetes with obesity", "firstAuthor": "Davies MJ", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2502082", "url": "https://doi.org/10.1056/NEJMoa2502082", "registryId": "NCT05394519", "drugIds": [ "cagrisema" ], "design": "rct", "populationEs": "1206 adultos con obesidad o sobrepeso y diabetes tipo 2.", "populationEn": "1,206 adults with obesity or overweight and type 2 diabetes.", "nParticipants": 1206, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso corporal y proporción con pérdida de al menos el 5 % a las 68 semanas, CagriSema frente a placebo.", "primaryOutcomeEn": "Percentage change in body weight and proportion losing at least 5% at 68 weeks, CagriSema versus placebo.", "resultSummaryEs": "En personas con diabetes tipo 2, CagriSema redujo el peso un 13,7 % a las 68 semanas, frente al 3,4 % con placebo; la diferencia estimada fue de −10,4 puntos porcentuales (IC 95 %: −11,2 a −9,5; p < 0,001). El 73,5 % de los tratados alcanzó una HbA1c del 6,5 % o menos, frente al 15,9 % con placebo. Como en otros ensayos, la pérdida de peso fue menor que en personas sin diabetes.", "resultSummaryEn": "In people with type 2 diabetes, CagriSema reduced weight by 13.7% at 68 weeks, compared with 3.4% on placebo; the estimated difference was −10.4 percentage points (95% CI, −11.2 to −9.5; p < 0.001). Of those treated, 73.5% reached an HbA1c of 6.5% or less, compared with 15.9% on placebo. As in other trials, weight loss was smaller than in people without diabetes.", "limitationsEs": "Financiado por Novo Nordisk. Sin comparador activo (no se comparó con semaglutida sola). El producto no estaba aprobado en ningún país en la fecha de revisión.", "limitationsEn": "Funded by Novo Nordisk. No active comparator (it was not compared with semaglutide alone). The product was not approved in any country as of the review date.", "sources": [ { "title": "Davies MJ, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025;393(7):648-659", "url": "https://doi.org/10.1056/NEJMoa2502082", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40544432 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40544432/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "REDEFINE 2", "pageUrl": "https://saciedad.com/estudios/redefine-2/", "pageUrlEn": "https://saciedad.com/en/studies/redefine-2/" }, { "id": "semaglutide-alcohol-use-disorder-hendershot", "title": "Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial", "titleEn": "Semaglutide for alcohol use disorder: a phase 2 trial", "firstAuthor": "Hendershot CS", "journal": "JAMA Psychiatry", "year": 2025, "doi": "10.1001/jamapsychiatry.2024.4789", "url": "https://doi.org/10.1001/jamapsychiatry.2024.4789", "registryId": "NCT05520775", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "48 adultos con trastorno por consumo de alcohol que no buscaban tratamiento, reclutados en un centro médico académico de Estados Unidos entre septiembre de 2022 y febrero de 2024; el 71 % eran mujeres y la edad media era de 39,9 años.", "populationEn": "48 adults with alcohol use disorder who were not seeking treatment, recruited at an academic medical center in the United States between September 2022 and February 2024; 71% were women and the mean age was 39.9 years.", "nParticipants": 48, "durationWeeks": 9, "primaryOutcomeEs": "Autoadministración de alcohol en laboratorio (gramos consumidos y concentración máxima de alcohol en aire espirado), medida antes y después del tratamiento.", "primaryOutcomeEn": "Laboratory alcohol self-administration (grams consumed and peak breath alcohol concentration), measured before and after treatment.", "resultSummaryEs": "Tras 9 semanas, la semaglutida a dosis bajas redujo frente a placebo los gramos de alcohol consumidos en una prueba de laboratorio (β −0,48; IC 95 %: −0,85 a −0,11) y la concentración máxima de alcohol en aire espirado (β −0,46; IC 95 %: −0,87 a −0,06), un efecto de tamaño medio o grande según los autores. No cambió la media de bebidas por día ni el número de días de consumo, pero redujo las bebidas por día de consumo (β −0,41; IC 95 %: −0,73 a −0,09) y el deseo semanal de beber (β −0,39; IC 95 %: −0,73 a −0,06). Fue un ensayo de fase 2, doble ciego, con dosis de 0,25 a 1 mg semanales. Los autores lo presentan como evidencia inicial que justifica ensayos más grandes.", "resultSummaryEn": "After 9 weeks, compared with placebo, low-dose semaglutide reduced the grams of alcohol consumed in a laboratory test (β −0.48; 95% CI, −0.85 to −0.11) and peak breath alcohol concentration (β −0.46; 95% CI, −0.87 to −0.06), a medium to large effect according to the authors. It did not change average drinks per day or the number of drinking days, but it reduced drinks per drinking day (β −0.41; 95% CI, −0.73 to −0.09) and weekly craving (β −0.39; 95% CI, −0.73 to −0.06). It was a double-blind phase 2 trial with doses of 0.25 to 1 mg once weekly. The authors present it as initial evidence that justifies larger trials.", "limitationsEs": "Muestra pequeña y tratamiento corto, propios de una fase 2; dosis bajas elegidas por seguridad, que pudieron limitar la detección de efectos; gravedad moderada del trastorno y participantes que no buscaban tratamiento. Financiado por el NIAAA y el NCATS (NIH); los financiadores no participaron en el diseño ni en el análisis. El tratamiento del consumo de alcohol no es una indicación autorizada de la semaglutida.", "limitationsEn": "Small sample and short treatment, typical of a phase 2 trial; low doses chosen for safety, which may have limited the detection of effects; moderate severity of the disorder and participants who were not seeking treatment. Funded by the NIAAA and the NCATS (NIH); the funders had no role in the design or the analysis. Treating alcohol use is not an approved indication for semaglutide.", "sources": [ { "title": "Hendershot CS, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(4):395-405", "url": "https://doi.org/10.1001/jamapsychiatry.2024.4789", "publisher": "JAMA Psychiatry", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 39937469 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/39937469/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC11822619 (methods, limitations, funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11822619/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "acronym": "Semaglutida y alcohol (fase 2)", "acronymEn": "Semaglutide and alcohol (phase 2)", "name": "Semaglutida y alcohol (fase 2)", "pageUrl": "https://saciedad.com/estudios/semaglutide-alcohol-use-disorder-hendershot/", "pageUrlEn": "https://saciedad.com/en/studies/semaglutide-alcohol-use-disorder-hendershot/" }, { "id": "soul", "acronym": "SOUL", "title": "Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes", "titleEn": "SOUL: oral semaglutide (Rybelsus) and heart outcomes in diabetes", "firstAuthor": "McGuire DK", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2501006", "url": "https://doi.org/10.1056/NEJMoa2501006", "registryId": "NCT03914326", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "9650 adultos de 50 años o más con diabetes tipo 2 (HbA1c del 6,5 al 10,0 %) y enfermedad cardiovascular aterosclerótica, enfermedad renal crónica o ambas, aleatorizados a semaglutida oral o placebo (4825 por grupo), además del tratamiento habitual.", "populationEn": "9,650 adults aged 50 or older with type 2 diabetes (HbA1c of 6.5 to 10.0%) and atherosclerotic cardiovascular disease, chronic kidney disease or both, randomized to oral semaglutide or placebo (4,825 per group), on top of standard care.", "nParticipants": 9650, "durationWeeks": null, "primaryOutcomeEs": "Primer evento cardiovascular mayor (muerte cardiovascular, infarto de miocardio no mortal o ictus no mortal) con semaglutida oral una vez al día (dosis máxima de 14 mg) frente a placebo, con hipótesis de superioridad; los eventos renales mayores fueron un objetivo secundario confirmatorio.", "primaryOutcomeEn": "First major cardiovascular event (cardiovascular death, nonfatal heart attack or nonfatal stroke) with once-daily oral semaglutide (maximum dose 14 mg) versus placebo, with a superiority hypothesis; major kidney events were a confirmatory secondary objective.", "resultSummaryEs": "Con un seguimiento medio de 47,5 meses, el evento cardiovascular mayor ocurrió en el 12,0 % de los participantes con semaglutida oral y en el 13,8 % con placebo (hazard ratio 0,86; IC 95 %: 0,77 a 0,96; p = 0,006). Eso equivale a 3,1 frente a 3,7 eventos por cada 100 personas y año. Los objetivos secundarios confirmatorios, entre ellos los eventos renales mayores, no difirieron de forma significativa entre grupos. Los efectos adversos graves afectaron al 47,9 % con semaglutida oral y al 50,3 % con placebo.", "resultSummaryEn": "Over a mean follow-up of 47.5 months, a major cardiovascular event occurred in 12.0% of participants on oral semaglutide and 13.8% on placebo (hazard ratio 0.86; 95% CI, 0.77 to 0.96; p = 0.006). That equals 3.1 versus 3.7 events per 100 person-years. The confirmatory secondary objectives, including major kidney events, did not differ significantly between groups. Serious adverse effects occurred in 47.9% on oral semaglutide and 50.3% on placebo.", "limitationsEs": "Financiado por Novo Nordisk, fabricante de la semaglutida. Solo incluyó a personas con diabetes tipo 2 y enfermedad cardiovascular o renal, así que no informa sobre personas sin diabetes. Estudió la semaglutida oral a dosis de hasta 14 mg al día, no la inyectable ni las dosis usadas para la obesidad.", "limitationsEn": "Funded by Novo Nordisk, which makes semaglutide. It only included people with type 2 diabetes and cardiovascular or kidney disease, so it says nothing about people without diabetes. It studied oral semaglutide at doses of up to 14 mg a day, not the injectable form or the doses used for obesity.", "sources": [ { "title": "McGuire DK, et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. N Engl J Med. 2025;392(20):2001-2012", "url": "https://doi.org/10.1056/NEJMoa2501006", "publisher": "New England Journal of Medicine", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 40162642 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40162642/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT03914326 (registration and primary outcome)", "url": "https://clinicaltrials.gov/study/NCT03914326", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "SOUL", "pageUrl": "https://saciedad.com/estudios/soul/", "pageUrlEn": "https://saciedad.com/en/studies/soul/" }, { "id": "step-up", "acronym": "STEP UP", "title": "Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial", "titleEn": "STEP UP: semaglutide 7.2 mg vs 2.4 mg for obesity", "firstAuthor": "Wharton S", "journal": "The Lancet Diabetes & Endocrinology", "year": 2025, "doi": "10.1016/S2213-8587(25)00226-8", "url": "https://doi.org/10.1016/S2213-8587(25)00226-8", "registryId": "NCT05646706", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "1407 adultos con obesidad (IMC de 30 o más) sin diabetes, en 95 centros de 11 países, aleatorizados a semaglutida 7,2 mg (1005), semaglutida 2,4 mg (201) o placebo (201); 73,7 % mujeres, edad media de 47 años, peso medio de 113,0 kg e IMC medio de 39,9.", "populationEn": "1,407 adults with obesity (BMI of 30 or more) without diabetes, at 95 sites in 11 countries, randomized to semaglutide 7.2 mg (1,005), semaglutide 2.4 mg (201) or placebo (201); 73.7% women, mean age 47 years, mean weight 113.0 kg and mean BMI 39.9.", "nParticipants": 1407, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual del peso y proporción de participantes que perdieron al menos un 5 % a las 72 semanas con semaglutida 7,2 mg semanal frente a placebo, ambos con intervención sobre el estilo de vida. La comparación con 2,4 mg fue un objetivo secundario confirmatorio.", "primaryOutcomeEn": "Percentage change in weight and proportion of participants losing at least 5% at 72 weeks with semaglutide 7.2 mg once weekly versus placebo, both with a lifestyle intervention. The comparison with 2.4 mg was a confirmatory secondary objective.", "resultSummaryEs": "A las 72 semanas, el peso cambió un −18,7 % con semaglutida 7,2 mg, un −15,6 % con 2,4 mg y un −3,9 % con placebo; la diferencia fue de −14,8 puntos porcentuales frente a placebo (IC 95 %: −16,2 a −13,4) y de −3,1 puntos frente a 2,4 mg (IC 95 %: −4,7 a −1,6). Con 7,2 mg fue más probable que con 2,4 mg perder al menos un 20 % del peso (OR 1,8; IC 95 %: 1,3 a 2,4) o un 25 % (OR 2,4; IC 95 %: 1,6 a 3,5). El perímetro de cintura bajó 11,7 cm más que con placebo (IC 95 %: −13,0 a −10,4). Los efectos adversos digestivos afectaron al 70,8 % con 7,2 mg, al 61,2 % con 2,4 mg y al 42,8 % con placebo, y la disestesia (sensaciones alteradas en la piel, como hormigueo) al 22,9 %, al 6,0 % y al 0,5 %, respectivamente.", "resultSummaryEn": "At 72 weeks, weight changed by −18.7% with semaglutide 7.2 mg, −15.6% with 2.4 mg and −3.9% with placebo; the difference was −14.8 percentage points versus placebo (95% CI, −16.2 to −13.4) and −3.1 points versus 2.4 mg (95% CI, −4.7 to −1.6). With 7.2 mg, losing at least 20% of weight (OR 1.8; 95% CI, 1.3 to 2.4) or 25% (OR 2.4; 95% CI, 1.6 to 3.5) was more likely than with 2.4 mg. Waist circumference fell 11.7 cm more than with placebo (95% CI, −13.0 to −10.4). Digestive adverse effects affected 70.8% on 7.2 mg, 61.2% on 2.4 mg and 42.8% on placebo, and dysesthesia (altered skin sensations, such as tingling) affected 22.9%, 6.0% and 0.5%, respectively.", "limitationsEs": "Financiado por Novo Nordisk. Excluyó a personas con diabetes (se estudiaron en el ensayo paralelo STEP UP T2D). El grupo de 2,4 mg fue pequeño (201 frente a 1005 con 7,2 mg) y la comparación entre dosis fue un objetivo secundario. Los resultados principales incluyen a quienes dejaron el tratamiento (estimando de política de tratamiento). Todos los participantes recibieron intervención sobre el estilo de vida.", "limitationsEn": "Funded by Novo Nordisk. People with diabetes were excluded (they were studied in the parallel STEP UP T2D trial). The 2.4 mg group was small (201 versus 1,005 on 7.2 mg) and the comparison between doses was a secondary objective. The main results include people who stopped treatment (treatment-policy estimand). All participants received a lifestyle intervention.", "sources": [ { "title": "Wharton S, et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949-963", "url": "https://doi.org/10.1016/S2213-8587(25)00226-8", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40961952 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40961952/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "STEP UP", "pageUrl": "https://saciedad.com/estudios/step-up/", "pageUrlEn": "https://saciedad.com/en/studies/step-up/" }, { "id": "step-up-t2d", "acronym": "STEP UP T2D", "title": "Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial", "titleEn": "STEP UP T2D: semaglutide 7.2 mg in obesity with type 2 diabetes", "firstAuthor": "Lingvay I", "journal": "The Lancet Diabetes & Endocrinology", "year": 2025, "doi": "10.1016/S2213-8587(25)00225-6", "url": "https://doi.org/10.1016/S2213-8587(25)00225-6", "registryId": "NCT05649137", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "512 adultos con obesidad (IMC de 30 o más) y diabetes tipo 2 (HbA1c del 7,0 al 10,0 %), en 68 centros de Bulgaria, Canadá, Hungría, Polonia, Portugal, Eslovaquia, Sudáfrica y Estados Unidos, aleatorizados a semaglutida 7,2 mg (307), semaglutida 2,4 mg (103) o placebo (102); 51,8 % mujeres, edad media de 56 años, peso medio de 110,1 kg, IMC medio de 38,6 y HbA1c media de 8,1 %.", "populationEn": "512 adults with obesity (BMI of 30 or more) and type 2 diabetes (HbA1c of 7.0 to 10.0%), at 68 sites in Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa and the United States, randomized to semaglutide 7.2 mg (307), semaglutide 2.4 mg (103) or placebo (102); 51.8% women, mean age 56 years, mean weight 110.1 kg, mean BMI 38.6 and mean HbA1c 8.1%.", "nParticipants": 512, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual del peso y proporción de participantes que perdieron al menos un 5 % a las 72 semanas con semaglutida 7,2 mg semanal frente a placebo, ambos con intervención sobre el estilo de vida.", "primaryOutcomeEn": "Percentage change in weight and share of participants who lost at least 5% at 72 weeks with semaglutide 7.2 mg once weekly versus placebo, both with a lifestyle intervention.", "resultSummaryEs": "A las 72 semanas, el peso había cambiado un −13,2 % con semaglutida 7,2 mg y un −3,9 % con placebo (diferencia de −9,3 puntos porcentuales; IC 95 %: −11,0 a −7,7). Frente a placebo, la HbA1c bajó 1,5 puntos más (IC 95 %: −1,8 a −1,2) y el perímetro de cintura 6,5 cm más (IC 95 %: −9,0 a −4,1). Los efectos adversos digestivos afectaron al 53,1 % con 7,2 mg, al 51,5 % con 2,4 mg y al 25,5 % con placebo, y la disestesia (sensaciones alteradas en la piel, como hormigueo) al 18,9 %, al 4,9 % y a nadie, respectivamente. Las hipoglucemias de nivel 2 o 3 fueron poco frecuentes y parecidas entre grupos.", "resultSummaryEn": "At 72 weeks, weight had changed by −13.2% with semaglutide 7.2 mg and by −3.9% with placebo (difference of −9.3 percentage points; 95% CI, −11.0 to −7.7). Compared with placebo, HbA1c fell by 1.5 points more (95% CI, −1.8 to −1.2) and waist circumference by 6.5 cm more (95% CI, −9.0 to −4.1). Digestive adverse effects affected 53.1% on 7.2 mg, 51.5% on 2.4 mg and 25.5% on placebo, and dysesthesia (altered skin sensations, such as tingling) 18.9%, 4.9% and no one, respectively. Level 2 or 3 hypoglycemia was uncommon and similar between groups.", "limitationsEs": "Financiado por Novo Nordisk. El objetivo principal comparó 7,2 mg con placebo, no con 2,4 mg, y el grupo de 2,4 mg fue pequeño (103 frente a 307). Todos los participantes recibieron intervención sobre el estilo de vida. La revista corrigió en 2026 algunos valores de tablas, figuras y un apéndice del artículo (triglicéridos iniciales, valores p y algunos intervalos de confianza); ninguno afecta a las cifras citadas aquí, que proceden del resumen.", "limitationsEn": "Funded by Novo Nordisk. The primary objective compared 7.2 mg with placebo, not with 2.4 mg, and the 2.4 mg group was small (103 versus 307). All participants received a lifestyle intervention. In 2026 the journal corrected some values in the paper's tables, figures and an appendix (baseline triglycerides, p values and some confidence intervals); none affects the figures cited here, which come from the abstract.", "sources": [ { "title": "Lingvay I, et al. Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):935-948", "url": "https://doi.org/10.1016/S2213-8587(25)00225-6", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 40961953 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40961953/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "Correction to Lancet Diabetes Endocrinol 2025; 13: 935-48. Lancet Diabetes Endocrinol. 2026;14(6):e9", "url": "https://doi.org/10.1016/S2213-8587(26)00078-1", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT05649137 (registration and primary outcomes)", "url": "https://clinicaltrials.gov/study/NCT05649137", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "STEP UP T2D", "pageUrl": "https://saciedad.com/estudios/step-up-t2d/", "pageUrlEn": "https://saciedad.com/en/studies/step-up-t2d/" }, { "id": "summit", "acronym": "SUMMIT", "title": "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity", "titleEn": "SUMMIT: tirzepatide for heart failure with obesity", "firstAuthor": "Packer M", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2410027", "url": "https://doi.org/10.1056/NEJMoa2410027", "registryId": "NCT04847557", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "731 adultos con insuficiencia cardiaca (clase II a IV de la NYHA), fracción de eyección del ventrículo izquierdo del 50 % o más e IMC de 30 o más, aleatorizados a tirzepatida hasta 15 mg semanal (364) o placebo (367) durante al menos 52 semanas. Según el registro del ensayo, podían participar personas con diabetes si la HbA1c era inferior al 9,5 %.", "populationEn": "731 adults with heart failure (NYHA class II to IV), a left ventricular ejection fraction of 50% or more and a BMI of 30 or more, randomized to tirzepatide up to 15 mg once weekly (364) or placebo (367) for at least 52 weeks. According to the trial registry, people with diabetes could take part if their HbA1c was below 9.5%.", "nParticipants": 731, "durationWeeks": 52, "primaryOutcomeEs": "Dos objetivos principales: el primer evento del compuesto de muerte cardiovascular o empeoramiento de la insuficiencia cardiaca, confirmado por un comité y analizado como tiempo hasta el primer evento, y el cambio a las 52 semanas en la puntuación clínica resumida del cuestionario de miocardiopatía de Kansas City (KCCQ-CSS, de 0 a 100, en la que más puntos indican mejor calidad de vida).", "primaryOutcomeEn": "Two primary objectives: the first event of the composite of cardiovascular death or worsening heart failure, confirmed by a committee and analyzed as time to first event, and the change at 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, from 0 to 100, where more points mean better quality of life).", "resultSummaryEs": "Con una mediana de seguimiento de 104 semanas, hubo muerte cardiovascular o empeoramiento de la insuficiencia cardiaca en 36 pacientes con tirzepatida (9,9 %) y en 56 con placebo (15,3 %) (hazard ratio 0,62; IC 95 %: 0,41 a 0,95). Los episodios de empeoramiento de la insuficiencia cardiaca se dieron en el 8,0 % frente al 14,2 % (hazard ratio 0,54; IC 95 %: 0,34 a 0,85), y la muerte cardiovascular, en el 2,2 % frente al 1,4 % (hazard ratio 1,58; IC 95 %: 0,52 a 4,83), un intervalo muy amplio porque solo hubo 8 y 5 muertes. A las 52 semanas, la puntuación KCCQ-CSS mejoró 19,5 puntos con tirzepatida y 12,7 con placebo (diferencia de 6,9 puntos; IC 95 %: 3,3 a 10,6). Dejaron el fármaco por efectos adversos, sobre todo digestivos, el 6,3 % con tirzepatida y el 1,4 % con placebo.", "resultSummaryEn": "Over a median follow-up of 104 weeks, cardiovascular death or worsening heart failure occurred in 36 patients on tirzepatide (9.9%) and 56 on placebo (15.3%) (hazard ratio 0.62; 95% CI, 0.41 to 0.95). Worsening heart-failure events occurred in 8.0% versus 14.2% (hazard ratio 0.54; 95% CI, 0.34 to 0.85), and cardiovascular death in 2.2% versus 1.4% (hazard ratio 1.58; 95% CI, 0.52 to 4.83), a very wide interval because there were only 8 and 5 deaths. At 52 weeks, the KCCQ-CSS score improved by 19.5 points with tirzepatide and 12.7 with placebo (difference of 6.9 points; 95% CI, 3.3 to 10.6). Adverse events, mainly digestive, led 6.3% on tirzepatide and 1.4% on placebo to stop the drug.", "limitationsEs": "Financiado por Eli Lilly, fabricante de la tirzepatida. Con 731 participantes y pocas muertes, no permite saber si la tirzepatida reduce la mortalidad cardiovascular; la reducción del objetivo compuesto se debió sobre todo a los episodios de empeoramiento de la insuficiencia cardiaca, que según el registro incluían, además de los ingresos hospitalarios, los aumentos del diurético oral. La mejora de síntomas se mide con un cuestionario que responden los propios participantes. Solo incluyó a personas con IMC de 30 o más.", "limitationsEn": "Funded by Eli Lilly, the maker of tirzepatide. With 731 participants and few deaths, it cannot show whether tirzepatide reduces cardiovascular mortality; the reduction in the composite outcome came mainly from worsening heart-failure events, which according to the registry included, besides hospital admissions, increases in oral diuretics. The improvement in symptoms is measured with a questionnaire that participants fill in themselves. It only included people with a BMI of 30 or more.", "sources": [ { "title": "Packer M, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025;392(5):427-437", "url": "https://doi.org/10.1056/NEJMoa2410027", "publisher": "New England Journal of Medicine", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 39555826 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/39555826/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT04847557 (eligibility and definition of heart-failure events)", "url": "https://clinicaltrials.gov/study/NCT04847557", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "SUMMIT", "pageUrl": "https://saciedad.com/estudios/summit/", "pageUrlEn": "https://saciedad.com/en/studies/summit/" }, { "id": "surmount-1-composicion-corporal", "acronym": "SURMOUNT-1 (composición corporal)", "acronymEn": "SURMOUNT-1 (body composition)", "title": "Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight", "titleEn": "SURMOUNT-1 body composition: fat vs lean mass on tirzepatide", "firstAuthor": "Look M", "journal": "Diabetes, Obesity and Metabolism", "year": 2025, "doi": "10.1111/dom.16275", "url": "https://doi.org/10.1111/dom.16275", "registryId": "NCT04184622", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "160 de los 2539 participantes de SURMOUNT-1 con densitometría al inicio y en la semana 72 (124 con tirzepatida, dosis agrupadas, y 36 con placebo); 73 % mujeres, peso medio de 102,5 kg e IMC medio de 38,0, sin diabetes.", "populationEn": "160 of the 2,539 SURMOUNT-1 participants with a DXA scan at baseline and at week 72 (124 on tirzepatide, doses pooled, and 36 on placebo); 73% women, mean weight 102.5 kg and mean BMI 38.0, without diabetes.", "nParticipants": 160, "durationWeeks": 72, "primaryOutcomeEs": "Cambio en peso, masa grasa y masa magra medidos por densitometría (DXA) desde el inicio hasta la semana 72, en conjunto y, de forma post hoc, por sexo, edad y tercil de pérdida de peso.", "primaryOutcomeEn": "Change in weight, fat mass and lean mass measured by DXA from baseline to week 72, overall and, post hoc, by sex, age and tertile of weight loss.", "resultSummaryEs": "A las 72 semanas, el peso cambió un −21,3 %, la masa grasa un −33,9 % y la masa magra un −10,9 % con tirzepatida, frente al −5,3 %, −8,2 % y −2,6 % con placebo (p < 0,001 en todas las comparaciones). Del peso perdido, aproximadamente el 75 % fue masa grasa y el 25 % masa magra, tanto con tirzepatida como con placebo. Estas proporciones se mantuvieron en la mayoría de los subgrupos por sexo, edad y magnitud de la pérdida de peso.", "resultSummaryEn": "At 72 weeks, weight changed by −21.3%, fat mass by −33.9% and lean mass by −10.9% with tirzepatide, compared with −5.3%, −8.2% and −2.6% on placebo (p < 0.001 for all comparisons). Of the weight lost, about 75% was fat mass and 25% lean mass, with both tirzepatide and placebo. These proportions held in most subgroups by sex, age and amount of weight lost.", "limitationsEs": "Ensayo financiado por Eli Lilly. Subestudio pequeño, con solo 36 participantes en el grupo placebo y las dosis de tirzepatida agrupadas. Los análisis por subgrupos fueron post hoc. La masa magra medida por DXA incluye órganos, agua y otros tejidos además del músculo.", "limitationsEn": "The trial was funded by Eli Lilly. A small substudy, with only 36 participants in the placebo group and the tirzepatide doses pooled. The subgroup analyses were post hoc. Lean mass measured by DXA includes organs, water and other tissues besides muscle.", "sources": [ { "title": "Look M, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025;27(5):2720-2729", "url": "https://doi.org/10.1111/dom.16275", "publisher": "Diabetes, Obesity and Metabolism", "accessed": "2026-09-23" }, { "title": "Europe PMC record PMID 39996356 (abstract; PMC11965027)", "url": "https://europepmc.org/article/MED/39996356", "publisher": "Europe PMC", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-1 (composición corporal)", "pageUrl": "https://saciedad.com/estudios/surmount-1-composicion-corporal/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-1-composicion-corporal/" }, { "id": "surmount-5", "acronym": "SURMOUNT-5", "title": "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity", "titleEn": "SURMOUNT-5: tirzepatide vs semaglutide (Zepbound vs Wegovy)", "firstAuthor": "Aronne LJ", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2416394", "url": "https://doi.org/10.1056/NEJMoa2416394", "registryId": "NCT05822830", "drugIds": [ "tirzepatida", "semaglutida" ], "design": "rct", "populationEs": "751 adultos con obesidad (o sobrepeso con al menos una complicación relacionada con el peso), sin diabetes.", "populationEn": "751 adults with obesity (or overweight with at least one weight-related complication), without diabetes.", "nParticipants": 751, "durationWeeks": 72, "primaryOutcomeEs": "Cambio porcentual del peso corporal a las 72 semanas con tirzepatida (dosis máxima tolerada de 10 o 15 mg) frente a semaglutida (dosis máxima tolerada de 1,7 o 2,4 mg).", "primaryOutcomeEn": "Percentage change in body weight at 72 weeks with tirzepatide (maximum tolerated dose of 10 or 15 mg) versus semaglutide (maximum tolerated dose of 1.7 or 2.4 mg).", "resultSummaryEs": "A las 72 semanas, el peso bajó un 20,2 % con tirzepatida (IC 95 %: −21,4 a −19,1) y un 13,7 % con semaglutida (IC 95 %: −14,9 a −12,6); la diferencia estimada fue de −6,5 puntos porcentuales (IC 95 %: −8,1 a −4,9; p < 0,001). Es la primera comparación directa entre ambos fármacos en obesidad. El perímetro de cintura se redujo 18,4 cm frente a 13,0 cm. Los efectos adversos más frecuentes fueron digestivos en ambos grupos.", "resultSummaryEn": "At 72 weeks, weight fell by 20.2% with tirzepatide (95% CI, −21.4 to −19.1) and 13.7% with semaglutide (95% CI, −14.9 to −12.6); the estimated difference was −6.5 percentage points (95% CI, −8.1 to −4.9; p < 0.001). It is the first head-to-head comparison of the two drugs in obesity. Waist circumference decreased by 18.4 cm versus 13.0 cm. The most common adverse effects were digestive in both groups.", "limitationsEs": "Financiado por Eli Lilly, fabricante de tirzepatida. Diseño abierto (los participantes sabían qué fármaco recibían), lo que puede influir en la adherencia y en los efectos notificados. Sin grupo placebo.", "limitationsEn": "Funded by Eli Lilly, the maker of tirzepatide. Open-label design (participants knew which drug they were getting), which can influence adherence and the effects reported. No placebo group.", "sources": [ { "title": "Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36", "url": "https://doi.org/10.1056/NEJMoa2416394", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 40353578 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/40353578/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-5", "pageUrl": "https://saciedad.com/estudios/surmount-5/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-5/" }, { "id": "surpass-cvot", "acronym": "SURPASS-CVOT", "title": "Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes", "titleEn": "SURPASS-CVOT: tirzepatide vs dulaglutide and heart outcomes", "firstAuthor": "Nicholls SJ", "journal": "New England Journal of Medicine", "year": 2025, "doi": "10.1056/NEJMoa2505928", "url": "https://doi.org/10.1056/NEJMoa2505928", "registryId": "NCT04255433", "drugIds": [ "tirzepatida", "dulaglutida" ], "design": "rct", "populationEs": "13 299 adultos de 40 años o más con diabetes tipo 2 y enfermedad cardiovascular aterosclerótica (HbA1c del 7 al 10,5 % e IMC de 25 o más), en 640 centros de 30 países; se analizaron 13 165 (edad media de 64,1 años, 29,0 % mujeres, IMC medio de 32,6, HbA1c media de 8,4 % y 14,7 años de diabetes de media).", "populationEn": "13,299 adults aged 40 or older with type 2 diabetes and atherosclerotic cardiovascular disease (HbA1c of 7 to 10.5% and BMI of 25 or more), at 640 sites in 30 countries; 13,165 were analyzed (mean age 64.1 years, 29.0% women, mean BMI 32.6, mean HbA1c 8.4% and an average of 14.7 years with diabetes).", "nParticipants": 13299, "durationWeeks": null, "primaryOutcomeEs": "Primer evento cardiovascular mayor (muerte cardiovascular, infarto de miocardio o ictus) con tirzepatida (hasta 15 mg semanales) frente a dulaglutida 1,5 mg semanal, con hipótesis principal de no inferioridad.", "primaryOutcomeEn": "First major cardiovascular event (cardiovascular death, heart attack or stroke) with tirzepatide (up to 15 mg once weekly) versus dulaglutide 1.5 mg once weekly, with a primary noninferiority hypothesis.", "resultSummaryEs": "Con una mediana de seguimiento de 4,0 años, el evento cardiovascular mayor ocurrió en el 12,2 % de los pacientes con tirzepatida y en el 13,1 % con dulaglutida (hazard ratio 0,92; IC 95,3 %: 0,83 a 1,01). Tirzepatida fue no inferior a dulaglutida (p = 0,003), pero la diferencia no alcanzó la significación estadística para demostrar superioridad (p = 0,09). La incidencia de efectos adversos fue parecida en ambos grupos, con más efectos digestivos con tirzepatida.", "resultSummaryEn": "Over a median follow-up of 4.0 years, a major cardiovascular event occurred in 12.2% of patients on tirzepatide and 13.1% on dulaglutide (hazard ratio 0.92; 95.3% CI, 0.83 to 1.01). Tirzepatide was noninferior to dulaglutide (p = 0.003), but the difference did not reach statistical significance for superiority (p = 0.09). The incidence of adverse effects was similar in both groups, with more digestive effects on tirzepatide.", "limitationsEs": "Financiado por Eli Lilly, que fabrica tanto la tirzepatida como la dulaglutida. Comparó con dulaglutida, un fármaco que ya había demostrado reducir los eventos cardiovasculares, y no con placebo, así que no mide el efecto de la tirzepatida frente a no recibir ninguno de los dos. Solo incluyó a personas con diabetes tipo 2 y enfermedad cardiovascular establecida.", "limitationsEn": "Funded by Eli Lilly, which makes both tirzepatide and dulaglutide. It compared tirzepatide with dulaglutide, a drug already shown to reduce cardiovascular events, and not with placebo, so it does not measure the effect of tirzepatide versus receiving neither drug. It only included people with type 2 diabetes and established cardiovascular disease.", "sources": [ { "title": "Nicholls SJ, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025;393(24):2409-2420", "url": "https://doi.org/10.1056/NEJMoa2505928", "publisher": "New England Journal of Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 41406444 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/41406444/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Zoungas S, et al. Tirzepatide and dulaglutide on major kidney events: pre-specified exploratory analyses of the SURPASS-CVOT trial. Lancet Diabetes Endocrinol. 2026;14(7):544-557 (sites, eligibility and median follow-up; PMID 42114520)", "url": "https://doi.org/10.1016/S2213-8587(26)00032-X", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURPASS-CVOT", "pageUrl": "https://saciedad.com/estudios/surpass-cvot/", "pageUrlEn": "https://saciedad.com/en/studies/surpass-cvot/" }, { "id": "achieve-2", "acronym": "ACHIEVE-2", "title": "Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial", "titleEn": "ACHIEVE-2: orforglipron vs dapagliflozin in type 2 diabetes", "firstAuthor": "Welch M", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)00800-7", "url": "https://doi.org/10.1016/S0140-6736(26)00800-7", "registryId": "NCT06192108", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "962 adultos con diabetes tipo 2 no controlada con metformina (HbA1c del 7,0 al 10,5 % e IMC de 23 o más), en 73 centros de seis países (China, Alemania, México, Polonia, Taiwán y Estados Unidos, según el registro); 49 % mujeres, edad media de 56,1 años, HbA1c media de 8,14 %, 8,0 años de diabetes de media e IMC medio de 32,6.", "populationEn": "962 adults with type 2 diabetes not controlled on metformin (HbA1c of 7.0 to 10.5% and BMI of 23 or more), at 73 sites in six countries (China, Germany, Mexico, Poland, Taiwan and the United States, per the registry); 49% women, mean age 56.1 years, mean HbA1c 8.14%, an average of 8.0 years with diabetes and mean BMI 32.6.", "nParticipants": 962, "durationWeeks": 40, "primaryOutcomeEs": "No inferioridad en el cambio de la HbA1c a las 40 semanas de orforglipron oral 3, 12 o 36 mg diarios frente a dapagliflozina 10 mg diaria (margen de 0,3 puntos), en un diseño abierto con la dosis de orforglipron enmascarada.", "primaryOutcomeEn": "Noninferiority in the change in HbA1c at 40 weeks of oral orforglipron 3, 12 or 36 mg daily versus dapagliflozin 10 mg daily (margin of 0.3 points), in an open-label design with the orforglipron dose masked.", "resultSummaryEs": "A las 40 semanas, la HbA1c bajó 1,23, 1,50 y 1,56 puntos con orforglipron 3, 12 y 36 mg, frente a 0,81 con dapagliflozina; las diferencias fueron de −0,42 (IC 95 %: −0,62 a −0,23), −0,70 (IC 95 %: −0,90 a −0,49) y −0,75 puntos (IC 95 %: −0,96 a −0,55), y las tres dosis fueron no inferiores y superiores a la dapagliflozina. Los efectos adversos digestivos, en su mayoría leves o moderados, afectaron a entre el 46 y el 54 % con orforglipron, frente al 12 % con dapagliflozina. Con las tres dosis de orforglipron, dejaron el tratamiento del estudio por cualquier motivo el 15, el 18 y el 20 %, frente al 6 % con dapagliflozina. No hubo hipoglucemias graves.", "resultSummaryEn": "At 40 weeks, HbA1c fell by 1.23, 1.50 and 1.56 points with orforglipron 3, 12 and 36 mg, compared with 0.81 on dapagliflozin; the differences were −0.42 (95% CI, −0.62 to −0.23), −0.70 (95% CI, −0.90 to −0.49) and −0.75 points (95% CI, −0.96 to −0.55), and all three doses were noninferior and superior to dapagliflozin. Digestive adverse effects, mostly mild or moderate, affected 46% to 54% on orforglipron, compared with 12% on dapagliflozin. On the three orforglipron doses, 15%, 18% and 20% stopped study treatment for any reason, compared with 6% on dapagliflozin. There was no severe hypoglycemia.", "limitationsEs": "Financiado por Eli Lilly, fabricante del orforglipron. Diseño abierto: los participantes sabían si tomaban orforglipron o dapagliflozina. Duró 40 semanas y solo incluyó a personas tratadas con metformina. El resumen publicado no informa del cambio de peso.", "limitationsEn": "Funded by Eli Lilly, which makes orforglipron. Open-label design: participants knew whether they were taking orforglipron or dapagliflozin. It lasted 40 weeks and only included people treated with metformin. The published abstract does not report the change in weight.", "sources": [ { "title": "Welch M, et al. Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2). Lancet. 2026;408(10550):125-140", "url": "https://doi.org/10.1016/S0140-6736(26)00800-7", "publisher": "The Lancet", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 42259339 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42259339/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT06192108 (registration and participating countries)", "url": "https://clinicaltrials.gov/study/NCT06192108", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "ACHIEVE-2", "pageUrl": "https://saciedad.com/estudios/achieve-2/", "pageUrlEn": "https://saciedad.com/en/studies/achieve-2/" }, { "id": "achieve-3", "acronym": "ACHIEVE-3", "title": "Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial", "titleEn": "ACHIEVE-3: orforglipron vs oral semaglutide in type 2 diabetes", "firstAuthor": "Rosenstock J", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)00202-3", "url": "https://doi.org/10.1016/S0140-6736(26)00202-3", "registryId": "NCT06045221", "drugIds": [ "orforglipron", "semaglutida" ], "design": "rct", "populationEs": "1698 adultos con diabetes tipo 2 insuficientemente controlada con metformina (HbA1c del 7,0 al 10,5 %, media de 8,3 %) e IMC de 25 o más, en Argentina, China, Japón, México y Estados Unidos.", "populationEn": "1,698 adults with type 2 diabetes inadequately controlled on metformin (HbA1c of 7.0 to 10.5%, mean 8.3%) and a BMI of 25 or more, in Argentina, China, Japan, Mexico and the United States.", "nParticipants": 1698, "durationWeeks": 52, "primaryOutcomeEs": "No inferioridad en el cambio de la HbA1c a las 52 semanas de orforglipron 36 mg frente a semaglutida oral 14 mg y de orforglipron 12 mg frente a semaglutida oral 7 mg (margen de 0,3 puntos).", "primaryOutcomeEn": "Noninferiority in HbA1c change at 52 weeks of orforglipron 36 mg versus oral semaglutide 14 mg and of orforglipron 12 mg versus oral semaglutide 7 mg (margin of 0.3 points).", "resultSummaryEs": "La HbA1c bajó 1,71 y 1,91 puntos con orforglipron 12 y 36 mg, y 1,23 y 1,47 puntos con semaglutida oral 7 y 14 mg. La diferencia de orforglipron 36 mg frente a semaglutida 14 mg fue de −0,44 puntos (IC 95 %: −0,62 a −0,26), y ambas dosis de orforglipron fueron superiores a ambas de semaglutida. Los efectos adversos digestivos (58-59 % frente a 37-45 %) y los abandonos por efectos adversos (9-10 % frente a 4-5 %) fueron más frecuentes con orforglipron, y el pulso aumentó más (3,7 a 4,7 frente a 1,0 a 1,5 latidos por minuto).", "resultSummaryEn": "HbA1c fell by 1.71 and 1.91 points with orforglipron 12 and 36 mg, and by 1.23 and 1.47 points with oral semaglutide 7 and 14 mg. The difference for orforglipron 36 mg versus semaglutide 14 mg was −0.44 points (95% CI, −0.62 to −0.26), and both orforglipron doses were superior to both semaglutide doses. Digestive adverse effects (58-59% versus 37-45%) and discontinuations because of adverse effects (9-10% versus 4-5%) were more frequent with orforglipron, and pulse rate rose more (3.7 to 4.7 versus 1.0 to 1.5 beats per minute).", "limitationsEs": "Financiado por Eli Lilly, fabricante del orforglipron. Diseño abierto (los participantes sabían qué fármaco tomaban). Solo incluyó personas con diabetes tipo 2 tratadas con metformina, y la semaglutida oral se usó a 7 y 14 mg, no a dosis más altas. No informa sobre personas sin diabetes.", "limitationsEn": "Funded by Eli Lilly, the maker of orforglipron. Open-label design (participants knew which drug they were taking). It only included people with type 2 diabetes treated with metformin, and oral semaglutide was used at 7 and 14 mg, not at higher doses. It says nothing about people without diabetes.", "sources": [ { "title": "Rosenstock J, et al. Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3). Lancet. 2026;407(10534):1147-1160", "url": "https://doi.org/10.1016/S0140-6736(26)00202-3", "publisher": "The Lancet", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 41765029 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/41765029/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "ACHIEVE-3", "pageUrl": "https://saciedad.com/estudios/achieve-3/", "pageUrlEn": "https://saciedad.com/en/studies/achieve-3/" }, { "id": "achieve-4", "acronym": "ACHIEVE-4", "title": "Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial", "titleEn": "ACHIEVE-4: heart safety of orforglipron vs insulin glargine", "firstAuthor": "Klein KR", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)01865-9", "url": "https://doi.org/10.1016/S0140-6736(26)01865-9", "registryId": "NCT05803421", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "2749 adultos con diabetes tipo 2 (HbA1c del 7,0 al 10,5 %), IMC de 25 o más y enfermedad cardiovascular establecida o enfermedad renal crónica, tratados con hasta tres antidiabéticos (metformina, una sulfonilurea o un inhibidor de SGLT2), en 317 centros de 16 países y territorios, entre ellos España, México y Argentina según el registro; 38 % mujeres, edad media de 63,1 años, HbA1c media de 8,2 % e IMC medio de 33. El 85,9 % tenía enfermedad cardiovascular establecida y el 37,6 %, enfermedad renal crónica.", "populationEn": "2,749 adults with type 2 diabetes (HbA1c of 7.0 to 10.5%), a BMI of 25 or more and established cardiovascular disease or chronic kidney disease, treated with up to three glucose-lowering drugs (metformin, a sulfonylurea or an SGLT2 inhibitor), at 317 sites in 16 countries and territories, including Spain, Mexico and Argentina per the registry; 38% women, mean age 63.1 years, mean HbA1c 8.2% and mean BMI 33. Of them, 85.9% had established cardiovascular disease and 37.6% had chronic kidney disease.", "nParticipants": 2749, "durationWeeks": null, "primaryOutcomeEs": "Tiempo hasta el primer evento cardiovascular mayor de cuatro componentes (MACE-4: muerte cardiovascular, infarto de miocardio no mortal, ictus no mortal u hospitalización por angina inestable) con orforglipron una vez al día a la dosis máxima tolerada (hasta 36 mg en cápsula, equivalentes al comprimido de 17,2 mg) frente a insulina glargina ajustada, en un diseño abierto y guiado por eventos; se declaraba la no inferioridad si el límite superior del IC 95 % del hazard ratio quedaba por debajo de 1,8.", "primaryOutcomeEn": "Time to the first four-component major adverse cardiovascular event (MACE-4: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for unstable angina) with once-daily orforglipron at the maximum tolerated dose (up to 36 mg as a capsule, equivalent to the 17.2 mg tablet) versus titrated insulin glargine, in an open-label, event-driven design; noninferiority was declared if the upper limit of the 95% CI of the hazard ratio was below 1.8.", "resultSummaryEs": "En una mediana de 2 años de seguimiento, hubo un evento cardiovascular mayor (MACE-4) en el 4,2 % con orforglipron y en el 5,0 % con insulina glargina (hazard ratio: 0,84; IC 95 %: 0,59 a 1,20), lo que demostró la no inferioridad, no una reducción del riesgo. Los efectos adversos digestivos afectaron al 62,1 % con orforglipron, frente al 14,2 % con insulina glargina, y fueron el motivo más frecuente para dejar el orforglipron. La hipoglucemia clínicamente significativa o grave (glucosa por debajo de 54 mg/dl) fue menos frecuente con orforglipron: 6,8 % frente a 19,2 %. Murieron 19 participantes (1,4 %) con orforglipron y 43 (3,2 %) con insulina glargina, y todas las muertes salvo una, en el grupo de insulina glargina, se consideraron no relacionadas con el tratamiento.", "resultSummaryEn": "Over a median follow-up of 2 years, a major adverse cardiovascular event (MACE-4) occurred in 4.2% on orforglipron and 5.0% on insulin glargine (hazard ratio, 0.84; 95% CI, 0.59 to 1.20), which showed noninferiority, not a reduction in risk. Digestive adverse effects affected 62.1% on orforglipron, compared with 14.2% on insulin glargine, and were the most common reason for stopping orforglipron. Clinically significant or severe hypoglycemia (glucose below 54 mg/dL) was less frequent on orforglipron: 6.8% versus 19.2%. There were 19 deaths (1.4%) on orforglipron and 43 (3.2%) on insulin glargine, and all deaths but one, in the insulin glargine group, were judged unrelated to treatment.", "limitationsEs": "Financiado por Eli Lilly, fabricante del orforglipron. Diseño abierto, con insulina glargina como comparador en lugar de placebo, y pensado para descartar un aumento del riesgo cardiovascular, no para demostrar que lo reduce; la mortalidad no era el objetivo principal. El resumen publicado no da los cambios de HbA1c ni de peso. En la fecha de revisión, el orforglipron no estaba aprobado para la diabetes tipo 2 en Estados Unidos.", "limitationsEn": "Funded by Eli Lilly, the maker of orforglipron. Open-label design, with insulin glargine rather than placebo as the comparator, built to rule out an increase in cardiovascular risk, not to show a reduction; death was not the primary outcome. The published abstract does not give the changes in HbA1c or weight. As of the review date, orforglipron was not approved for type 2 diabetes in the United States.", "sources": [ { "title": "Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4). Lancet. Published online September 30, 2026", "url": "https://doi.org/10.1016/S0140-6736(26)01865-9", "publisher": "The Lancet", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42815506 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42815506/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT05803421 (ACHIEVE-4: registration and participating countries)", "url": "https://clinicaltrials.gov/study/NCT05803421", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "ACHIEVE-4", "pageUrl": "https://saciedad.com/estudios/achieve-4/", "pageUrlEn": "https://saciedad.com/en/studies/achieve-4/" }, { "id": "achieve-5", "acronym": "ACHIEVE-5", "title": "Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial", "titleEn": "ACHIEVE-5: orforglipron added to insulin glargine in T2D", "firstAuthor": "Giorgino F", "journal": "JAMA", "year": 2026, "doi": "10.1001/jama.2026.9512", "url": "https://doi.org/10.1001/jama.2026.9512", "registryId": "NCT06109311", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "546 adultos con diabetes tipo 2 insuficientemente controlada con insulina glargina, con o sin metformina o inhibidores de SGLT2, en 72 centros de Estados Unidos, Brasil, China, Japón y Rumanía; mediana de edad de 61,0 años, 52,9 % hombres, mediana de 14,6 años con diabetes, HbA1c media de 8,50 % e IMC medio de 30,8.", "populationEn": "546 adults with type 2 diabetes inadequately controlled on insulin glargine, with or without metformin or SGLT2 inhibitors, at 72 sites in the United States, Brazil, China, Japan and Romania; median age 61.0 years, 52.9% men, a median of 14.6 years with diabetes, mean HbA1c 8.50% and mean BMI 30.8.", "nParticipants": 546, "durationWeeks": 40, "primaryOutcomeEs": "Cambio de la HbA1c a las 40 semanas con orforglipron 12 y 36 mg diarios frente a placebo, añadidos a insulina glargina ajustada, en un diseño doble ciego; la dosis de 3 mg fue un objetivo secundario clave.", "primaryOutcomeEn": "Change in HbA1c at 40 weeks with orforglipron 12 and 36 mg daily versus placebo, added to titrated insulin glargine, in a double-blind design; the 3 mg dose was a key secondary outcome.", "resultSummaryEs": "A las 40 semanas, la HbA1c bajó 1,58, 1,88 y 1,82 puntos con orforglipron 3, 12 y 36 mg, frente a 0,79 con placebo; las diferencias fueron de −0,78 (IC 95 %: −1,02 a −0,55), −1,08 (IC 95 %: −1,33 a −0,83) y −1,03 puntos (IC 95 %: −1,28 a −0,77), y las tres dosis fueron superiores al placebo. El peso cambió un −2,6 %, un −4,8 % y un −5,4 % con las tres dosis, frente a un +0,2 % con placebo. Los efectos adversos más frecuentes con orforglipron fueron digestivos, de intensidad leve a moderada, y el orforglipron no aumentó el riesgo de hipoglucemia clínicamente significativa frente a placebo. Completaron el ensayo 507 de los 546 participantes (92,9 %).", "resultSummaryEn": "At 40 weeks, HbA1c fell by 1.58, 1.88 and 1.82 points with orforglipron 3, 12 and 36 mg, compared with 0.79 on placebo; the differences were −0.78 (95% CI, −1.02 to −0.55), −1.08 (95% CI, −1.33 to −0.83) and −1.03 points (95% CI, −1.28 to −0.77), and all three doses were superior to placebo. Weight changed by −2.6%, −4.8% and −5.4% on the three doses, compared with +0.2% on placebo. The most common adverse effects on orforglipron were digestive, mild to moderate in severity, and orforglipron did not increase the risk of clinically significant hypoglycemia compared with placebo. Of the 546 participants, 507 (92.9%) completed the trial.", "limitationsEs": "Financiado por Eli Lilly, fabricante del orforglipron, según el registro del ensayo. Duró 40 semanas y solo incluyó a personas que ya usaban insulina glargina, cuya dosis se ajustaba durante el estudio. El resumen publicado no indica si las cifras cuentan a quienes dejaron el tratamiento (el estimando) ni da los porcentajes de cada efecto adverso o de abandonos del tratamiento. En la fecha de revisión, el orforglipron no estaba aprobado para la diabetes tipo 2 en Estados Unidos.", "limitationsEn": "Funded by Eli Lilly, the maker of orforglipron, according to the trial registry. It lasted 40 weeks and only included people already using insulin glargine, whose dose was adjusted during the study. The published abstract does not say whether the figures count people who stopped treatment (the estimand), nor does it give the rates of each adverse effect or of treatment discontinuation. As of the review date, orforglipron was not approved for type 2 diabetes in the United States.", "sources": [ { "title": "Giorgino F, et al. Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. JAMA. 2026;336(5):389-399", "url": "https://doi.org/10.1001/jama.2026.9512", "publisher": "JAMA (American Medical Association)", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42251769 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42251769/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT06109311 (ACHIEVE-5: registration, sponsor and masking)", "url": "https://clinicaltrials.gov/study/NCT06109311", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "ACHIEVE-5", "pageUrl": "https://saciedad.com/estudios/achieve-5/", "pageUrlEn": "https://saciedad.com/en/studies/achieve-5/" }, { "id": "achieve-j", "acronym": "ACHIEVE-J", "title": "Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial", "titleEn": "ACHIEVE-J: long-term safety of orforglipron in Japanese adults", "firstAuthor": "Yabe D", "journal": "The Lancet Diabetes & Endocrinology", "year": 2026, "doi": "10.1016/S2213-8587(26)00138-5", "url": "https://doi.org/10.1016/S2213-8587(26)00138-5", "registryId": "NCT06010004", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "401 adultos japoneses con diabetes tipo 2 tratados solo con dieta y ejercicio o con uno o dos antidiabéticos orales, en 40 centros de Japón.", "populationEn": "401 Japanese adults with type 2 diabetes managed with diet and exercise alone or with one or two oral glucose-lowering drugs, at 40 centers in Japan.", "nParticipants": 401, "durationWeeks": 52, "primaryOutcomeEs": "Seguridad durante 52 semanas (efectos adversos) con orforglipron oral 3, 12 o 36 mg diarios, asignados al azar y en abierto, sin grupo placebo ni comparador.", "primaryOutcomeEn": "Safety over 52 weeks (adverse events) with oral orforglipron 3, 12 or 36 mg daily, randomly assigned and open-label, with no placebo or comparator group.", "resultSummaryEs": "En 52 semanas, el 85 % de los participantes tuvo al menos un efecto adverso (81 %, 84 % y 88 % con 3, 12 y 36 mg), en la mayoría de los casos leve (67 %) o moderado (16 %). Dejaron el tratamiento por efectos adversos el 5 %, el 8 % y el 14 % con 3, 12 y 36 mg, sobre todo por síntomas digestivos (3,8 %, 5,9 % y 8,2 %). Hubo hipoglucemia de nivel 2 (glucosa por debajo de 54 mg/dl) en 3 participantes con 12 mg y en 3 con 36 mg (2 % en cada grupo), y ninguna hipoglucemia grave. Completaron el tratamiento del estudio 352 de los 401 participantes (88 %).", "resultSummaryEn": "Over 52 weeks, 85% of participants had at least one adverse event (81%, 84% and 88% on 3, 12 and 36 mg), mostly mild (67%) or moderate (16%). Discontinuations because of adverse events occurred in 5%, 8% and 14% on 3, 12 and 36 mg, mostly because of digestive symptoms (3.8%, 5.9% and 8.2%). Level 2 hypoglycemia (glucose below 54 mg/dL) occurred in 3 participants on 12 mg and 3 on 36 mg (2% in each group), and there was no severe hypoglycemia. Of the 401 participants, 352 (88%) completed study treatment.", "limitationsEs": "Financiado por Eli Lilly, fabricante del orforglipron. Diseño abierto y sin grupo placebo ni comparador, así que no permite saber qué parte de los efectos adversos se debe al fármaco. Solo incluyó a personas japonesas, con un objetivo de seguridad y no de eficacia. El resumen publicado no da los cambios de HbA1c ni de peso.", "limitationsEn": "Funded by Eli Lilly, the maker of orforglipron. Open-label design with no placebo or comparator group, so it cannot show how much of the adverse events is due to the drug. It only included Japanese people, with a safety rather than an efficacy goal. The published abstract does not give the changes in HbA1c or weight.", "sources": [ { "title": "Yabe D, et al. Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J). Lancet Diabetes Endocrinol. 2026;14(10):841-855", "url": "https://doi.org/10.1016/S2213-8587(26)00138-5", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42607698 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42607698/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT06010004 (ACHIEVE-J: registration)", "url": "https://clinicaltrials.gov/study/NCT06010004", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "ACHIEVE-J", "pageUrl": "https://saciedad.com/estudios/achieve-j/", "pageUrlEn": "https://saciedad.com/en/studies/achieve-j/" }, { "id": "attain-maintain", "acronym": "ATTAIN-MAINTAIN", "title": "Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial", "titleEn": "ATTAIN-MAINTAIN: the orforglipron pill after weight-loss shots", "firstAuthor": "Aronne LJ", "journal": "Nature Medicine", "year": 2026, "doi": "10.1038/s41591-026-04386-7", "url": "https://doi.org/10.1038/s41591-026-04386-7", "registryId": "NCT06584916", "drugIds": [ "orforglipron" ], "design": "rct", "populationEs": "376 adultos sin diabetes que habían completado las 72 semanas del ensayo SURMOUNT-5 con tirzepatida (205, cohorte 1) o semaglutida (171, cohorte 2) y perdido al menos un 5 % del peso, en 29 centros de Estados Unidos, aleatorizados (3:2) a orforglipron o placebo. Peso medio al entrar de 90,1 kg en la cohorte de tirzepatida y de 94,4 kg en la de semaglutida.", "populationEn": "376 adults without diabetes who had completed the 72 weeks of the SURMOUNT-5 trial on tirzepatide (205, cohort 1) or semaglutide (171, cohort 2) and lost at least 5% of their weight, at 29 sites in the United States, randomized (3:2) to orforglipron or placebo. Mean weight on entry was 90.1 kg in the tirzepatide cohort and 94.4 kg in the semaglutide cohort.", "nParticipants": 376, "durationWeeks": 52, "primaryOutcomeEs": "Porcentaje de la pérdida de peso lograda en SURMOUNT-5 que se mantenía a las 52 semanas con orforglipron oral diario (36 mg o la dosis máxima tolerada de 24 o 36 mg en cápsulas de investigación, equivalentes a 14,5 y 17,2 mg en comprimidos) frente a placebo, en quienes habían alcanzado una meseta de peso (cambio de menos del 5 % entre las semanas 60 y 72 de SURMOUNT-5). Cada cohorte se analizó por separado.", "primaryOutcomeEn": "Share of the weight loss achieved in SURMOUNT-5 that was maintained at 52 weeks with daily oral orforglipron (36 mg or the maximum tolerated dose of 24 or 36 mg as investigational capsules, equivalent to 14.5 and 17.2 mg tablets) versus placebo, in participants who had reached a weight plateau (less than 5% change between weeks 60 and 72 of SURMOUNT-5). Each cohort was analyzed separately.", "resultSummaryEs": "Con orforglipron se mantuvo el 74,7 % del peso perdido con tirzepatida, frente al 49,2 % con placebo (diferencia de 25,5 puntos; IC 95 %: 14,5 a 36,5); tras semaglutida, el 79,3 % frente al 37,6 % (diferencia de 41,7 puntos; IC 95 %: 24,4 a 59,0). Estas cifras corresponden a quienes habían alcanzado la meseta de peso, y se cumplieron todos los objetivos secundarios clave. Los efectos adversos más frecuentes fueron digestivos, en su mayoría leves o moderados, y dejaron el tratamiento por efectos adversos entre el 4,8 y el 7,3 % con orforglipron, frente al 2,5 y el 3,0 % con placebo.", "resultSummaryEn": "On orforglipron, 74.7% of the weight lost on tirzepatide was maintained, versus 49.2% on placebo (difference of 25.5 points; 95% CI, 14.5 to 36.5); after semaglutide, 79.3% versus 37.6% (difference of 41.7 points; 95% CI, 24.4 to 59.0). These figures refer to participants who had reached the weight plateau, and all key secondary objectives were met. The most common adverse effects were digestive, mostly mild or moderate, and between 4.8% and 7.3% stopped orforglipron because of adverse effects, versus 2.5% and 3.0% on placebo.", "limitationsEs": "Financiado por Eli Lilly, fabricante del orforglipron y de la tirzepatida. No hubo un grupo que siguiera con el inyectable, así que no compara el orforglipron con continuar la tirzepatida o la semaglutida. Duró un año, solo en Estados Unidos y con personas sin diabetes que venían de otro ensayo. Las dosis se expresan en cápsulas de investigación; el producto aprobado en Estados Unidos usa comprimidos con otras etiquetas de dosis.", "limitationsEn": "Funded by Eli Lilly, which makes orforglipron and tirzepatide. There was no group that stayed on the injectable, so it does not compare orforglipron with continuing tirzepatide or semaglutide. It lasted one year, only in the United States and with people without diabetes who came from another trial. Doses are given as investigational capsules; the product approved in the United States uses tablets with different dose labels.", "sources": [ { "title": "Aronne LJ, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med. 2026;32(7):2679-2687", "url": "https://doi.org/10.1038/s41591-026-04386-7", "publisher": "Nature Medicine", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 42120723 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42120723/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "PubMed Central full text PMC13375559 (sites, doses, baseline weight and discontinuations)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13375559/", "publisher": "National Library of Medicine (PubMed Central)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT06584916 (registration and enrolment)", "url": "https://clinicaltrials.gov/study/NCT06584916", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "ATTAIN-MAINTAIN", "pageUrl": "https://saciedad.com/estudios/attain-maintain/", "pageUrlEn": "https://saciedad.com/en/studies/attain-maintain/" }, { "id": "evoke", "acronym": "evoke y evoke+", "acronymEn": "evoke and evoke+", "multipleTrials": true, "title": "Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials", "titleEn": "evoke and evoke+: oral semaglutide in early Alzheimer's disease", "firstAuthor": "Cummings JL", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)00459-9", "url": "https://doi.org/10.1016/S0140-6736(26)00459-9", "registryId": "NCT04777396", "drugIds": [ "semaglutida" ], "design": "rct", "populationEs": "3808 personas de 55 a 85 años con enfermedad de Alzheimer confirmada por amiloide, en fase de deterioro cognitivo leve o demencia leve, en 566 centros de 40 países: 1855 en evoke y 1953 en evoke+, que admitía enfermedad de pequeño vaso significativa; edad media de 72,2 años.", "populationEn": "3,808 people aged 55 to 85 with amyloid-confirmed Alzheimer's disease at the stage of mild cognitive impairment or mild dementia, at 566 sites in 40 countries: 1,855 in evoke and 1,953 in evoke+, which admitted significant small vessel disease; mean age 72.2 years.", "nParticipants": 3808, "durationWeeks": 104, "primaryOutcomeEs": "Cambio en la escala CDR-SB (Clinical Dementia Rating-Sum of Boxes, que mide la progresión clínica de la demencia) desde el inicio hasta la semana 104 con semaglutida oral una vez al día (hasta 14 mg, dosis flexible) frente a placebo, con tratamiento previsto de hasta 156 semanas.", "primaryOutcomeEn": "Change in the CDR-SB scale (Clinical Dementia Rating-Sum of Boxes, which measures the clinical progression of dementia) from baseline to week 104 with once-daily oral semaglutide (up to 14 mg, flexible dose) versus placebo, with planned treatment of up to 156 weeks.", "resultSummaryEs": "A las 104 semanas, la escala CDR-SB empeoró 2,3 y 2,2 puntos con semaglutida en evoke y evoke+, y 2,3 y 2,1 con placebo, sin diferencias significativas. Las diferencias fueron de −0,08 puntos en evoke (IC 95 %: −0,35 a 0,20; p = 0,57) y de 0,10 en evoke+ (IC 95 %: −0,17 a 0,38; p = 0,46). Hubo efectos adversos durante el tratamiento en el 91,2 % con semaglutida y en el 84,8 % con placebo. La semaglutida oral no frenó la progresión clínica, y ambos ensayos se interrumpieron por ese resultado negativo.", "resultSummaryEn": "At 104 weeks, CDR-SB worsened by 2.3 and 2.2 points on semaglutide in evoke and evoke+ and by 2.3 and 2.1 on placebo, with no significant differences. The differences were −0.08 points in evoke (95% CI, −0.35 to 0.20; p = 0.57) and 0.10 in evoke+ (95% CI, −0.17 to 0.38; p = 0.46). Adverse effects during treatment occurred in 91.2% on semaglutide and 84.8% on placebo. Oral semaglutide did not slow clinical progression, and both trials were stopped because of that negative result.", "limitationsEs": "Financiado por Novo Nordisk, fabricante de la semaglutida. Estudió semaglutida oral de hasta 14 mg al día en personas que ya tenían síntomas de Alzheimer, no la inyectable ni la prevención de la demencia. Los indicios previos de un menor riesgo de demencia con estos fármacos procedían sobre todo de personas con diabetes tipo 2 u obesidad, no de personas con Alzheimer ya diagnosticado. No se diseñó para evaluar el peso ni la diabetes.", "limitationsEn": "Funded by Novo Nordisk, which makes semaglutide. It studied oral semaglutide of up to 14 mg a day in people who already had Alzheimer's symptoms, not the injectable form or the prevention of dementia. Earlier signs of a lower dementia risk with these drugs came mainly from people with type 2 diabetes or obesity, not from people already diagnosed with Alzheimer's. It was not designed to assess weight or diabetes.", "sources": [ { "title": "Cummings JL, et al. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+). Lancet. 2026;407(10544):2167-2179", "url": "https://doi.org/10.1016/S0140-6736(26)00459-9", "publisher": "The Lancet", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 41865758 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/41865758/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT04777396 (evoke: registration and primary outcome)", "url": "https://clinicaltrials.gov/study/NCT04777396", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT04777409 (evoke+: registration and primary outcome)", "url": "https://clinicaltrials.gov/study/NCT04777409", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "evoke y evoke+", "pageUrl": "https://saciedad.com/estudios/evoke/", "pageUrlEn": "https://saciedad.com/en/studies/evoke/" }, { "id": "redefine-5", "acronym": "REDEFINE 5", "title": "Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial", "titleEn": "REDEFINE 5: CagriSema vs semaglutide in Japan and Taiwan", "firstAuthor": "Yamauchi T", "journal": "The Lancet Diabetes & Endocrinology", "year": 2026, "doi": "10.1016/S2213-8587(25)00402-4", "url": "https://doi.org/10.1016/S2213-8587(25)00402-4", "registryId": "NCT05813925", "drugIds": [ "cagrisema", "semaglutida" ], "design": "rct", "populationEs": "331 adultos de Japón y Taiwán con sobrepeso u obesidad según los criterios japoneses (IMC de 27 o más con al menos dos complicaciones relacionadas con la obesidad, o de 35 o más con al menos una), con o sin diabetes tipo 2, en 21 centros de Japón y uno de Taiwán: 164 asignados a CagriSema y 167 a semaglutida 2,4 mg sola. El 68 % eran hombres y el 24 % tenía diabetes tipo 2.", "populationEn": "331 adults in Japan and Taiwan with overweight or obesity by Japanese criteria (a BMI of 27 or more with at least two obesity-related complications, or 35 or more with at least one), with or without type 2 diabetes, at 21 sites in Japan and one in Taiwan: 164 assigned to CagriSema and 167 to semaglutide 2.4 mg alone. Of the participants, 68% were men and 24% had type 2 diabetes.", "nParticipants": 331, "durationWeeks": 68, "primaryOutcomeEs": "Cambio porcentual del peso a las 68 semanas con CagriSema (cagrilintida 2,4 mg más semaglutida 2,4 mg, una vez por semana) frente a semaglutida 2,4 mg sola, ambas con cambios en el estilo de vida y en doble ciego.", "primaryOutcomeEn": "Percentage change in body weight at 68 weeks with CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg, once weekly) versus semaglutide 2.4 mg alone, both with lifestyle changes and double-blind.", "resultSummaryEs": "A las 68 semanas, el peso bajó un 18,4 % con CagriSema y un 11,9 % con semaglutida 2,4 mg sola; la diferencia estimada fue de −6,5 puntos porcentuales (IC 95 %: −8,4 a −4,6; p < 0,0001). El análisis principal usó el estimando del producto en estudio, que supone que todos tomaron el tratamiento como se pretendía, así que estas cifras no son comparables con las de REDEFINE 1. Dejó el tratamiento el 10 % con CagriSema y el 6 % con semaglutida. Hubo efectos adversos en el 87 % y el 84 %, sobre todo digestivos (53 % y 51 %); hubo una muerte en el grupo de semaglutida, que el investigador no atribuyó al tratamiento.", "resultSummaryEn": "At 68 weeks, weight fell by 18.4% on CagriSema and 11.9% on semaglutide 2.4 mg alone; the estimated difference was −6.5 percentage points (95% CI, −8.4 to −4.6; p < 0.0001). The main analysis used the trial product estimand, which assumes everyone took the treatment as intended, so these figures are not comparable with those of REDEFINE 1. Treatment was stopped by 10% on CagriSema and 6% on semaglutide. Adverse events occurred in 87% and 84%, mostly digestive (53% and 51%); there was one death in the semaglutide group, which the investigator did not attribute to treatment.", "limitationsEs": "Financiado por Novo Nordisk, que fabrica CagriSema y la semaglutida. Solo incluyó a personas de Japón y Taiwán, con los criterios de obesidad japoneses. El análisis principal supone que todos siguieron el tratamiento, por lo que da cifras mayores que el estimando de régimen de tratamiento que usan otros ensayos. No tuvo grupo placebo. El producto no estaba aprobado en ningún país en la fecha de revisión.", "limitationsEn": "Funded by Novo Nordisk, which makes CagriSema and semaglutide. It only included people in Japan and Taiwan, using the Japanese obesity criteria. The main analysis assumes everyone stayed on treatment, so it gives larger figures than the treatment-regimen estimand other trials use. There was no placebo group. The product was not approved in any country as of the review date.", "sources": [ { "title": "Yamauchi T, et al. Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5). Lancet Diabetes Endocrinol. 2026;14(6):450-462", "url": "https://doi.org/10.1016/S2213-8587(25)00402-4", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42009015 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42009015/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT05813925 (REDEFINE 5: registration, eligibility and enrollment)", "url": "https://clinicaltrials.gov/study/NCT05813925", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "REDEFINE 5", "pageUrl": "https://saciedad.com/estudios/redefine-5/", "pageUrlEn": "https://saciedad.com/en/studies/redefine-5/" }, { "id": "reimagine-2", "acronym": "REIMAGINE 2", "title": "Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study", "titleEn": "REIMAGINE 2: CagriSema vs semaglutide in type 2 diabetes", "firstAuthor": "Buse JB", "journal": "The Lancet Diabetes & Endocrinology", "year": 2026, "doi": "10.1016/S2213-8587(26)00125-7", "url": "https://doi.org/10.1016/S2213-8587(26)00125-7", "registryId": "NCT06065540", "drugIds": [ "cagrisema", "semaglutida" ], "design": "rct", "populationEs": "2713 adultos con diabetes tipo 2 no controlada (HbA1c del 7,0 al 10,5 %) a pesar de la metformina, con o sin un inhibidor de SGLT2, y con un IMC de 25 o más, en 30 países: 603 asignados a CagriSema 2,4 + 2,4 mg, 605 a semaglutida 2,4 mg, 152 a cagrilintida 2,4 mg, 595 a CagriSema 1,0 + 1,0 mg, 609 a semaglutida 1,0 mg y 149 a placebo. La HbA1c inicial media era del 8,2 %. El registro de ClinicalTrials.gov da 2734 participantes.", "populationEn": "2,713 adults with type 2 diabetes not controlled (HbA1c 7.0% to 10.5%) despite metformin, with or without an SGLT2 inhibitor, and a BMI of 25 or more, in 30 countries: 603 assigned to CagriSema 2.4 + 2.4 mg, 605 to semaglutide 2.4 mg, 152 to cagrilintide 2.4 mg, 595 to CagriSema 1.0 + 1.0 mg, 609 to semaglutide 1.0 mg and 149 to placebo. Mean baseline HbA1c was 8.2%. The ClinicalTrials.gov registry lists 2,734 participants.", "nParticipants": 2713, "durationWeeks": 68, "primaryOutcomeEs": "Cambio de la HbA1c a las 68 semanas con CagriSema (cagrilintida 2,4 mg más semaglutida 2,4 mg, una vez por semana) frente a semaglutida 2,4 mg sola.", "primaryOutcomeEn": "Change in HbA1c at 68 weeks with CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg, once weekly) versus semaglutide 2.4 mg alone.", "resultSummaryEs": "A las 68 semanas, la HbA1c bajó 1,91 puntos con CagriSema 2,4 + 2,4 mg y 1,75 con semaglutida 2,4 mg sola; la diferencia estimada fue de −0,16 puntos (IC 95 %: −0,27 a −0,05; p = 0,0035), con el estimando de eficacia. Completó el estudio el 95,7 % de los participantes, y el 87,6 % seguía con el tratamiento en la semana 68. Hubo efectos adversos en el 86,9 % con CagriSema 2,4 + 2,4 mg, el 81,2 % con semaglutida 2,4 mg, el 82,2 % con cagrilintida 2,4 mg, el 81,6 % con CagriSema 1,0 + 1,0 mg, el 78,5 % con semaglutida 1,0 mg y el 70,5 % con placebo; los más frecuentes fueron digestivos.", "resultSummaryEn": "At 68 weeks, HbA1c fell by 1.91 points on CagriSema 2.4 + 2.4 mg and 1.75 on semaglutide 2.4 mg alone; the estimated difference was −0.16 points (95% CI, −0.27 to −0.05; p = 0.0035), using the efficacy estimand. Of the participants, 95.7% completed the study and 87.6% were still on treatment at week 68. Adverse events occurred in 86.9% on CagriSema 2.4 + 2.4 mg, 81.2% on semaglutide 2.4 mg, 82.2% on cagrilintide 2.4 mg, 81.6% on CagriSema 1.0 + 1.0 mg, 78.5% on semaglutide 1.0 mg and 70.5% on placebo; the most common were digestive.", "limitationsEs": "Financiado por Novo Nordisk, que fabrica CagriSema y la semaglutida. La ventaja en HbA1c frente a semaglutida sola fue pequeña (0,16 puntos), aunque estadísticamente significativa. El análisis principal usó el estimando de eficacia, que supone que todos siguieron el tratamiento. El resumen del artículo no da los cambios de peso. El producto no estaba aprobado en ningún país en la fecha de revisión.", "limitationsEn": "Funded by Novo Nordisk, which makes CagriSema and semaglutide. The HbA1c advantage over semaglutide alone was small (0.16 points), although statistically significant. The main analysis used the efficacy estimand, which assumes everyone stayed on treatment. The paper’s abstract does not give the changes in weight. The product was not approved in any country as of the review date.", "sources": [ { "title": "Buse JB, et al. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2). Lancet Diabetes Endocrinol. 2026;14(8):662-677", "url": "https://doi.org/10.1016/S2213-8587(26)00125-7", "publisher": "The Lancet Diabetes & Endocrinology", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42251859 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42251859/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT06065540 (REIMAGINE 2: registration, eligibility and enrollment)", "url": "https://clinicaltrials.gov/study/NCT06065540", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "REIMAGINE 2", "pageUrl": "https://saciedad.com/estudios/reimagine-2/", "pageUrlEn": "https://saciedad.com/en/studies/reimagine-2/" }, { "id": "surmount-4-cardiometabolico-post-hoc", "acronym": "SURMOUNT-4 (análisis post hoc)", "acronymEn": "SURMOUNT-4 (post hoc analysis)", "title": "Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial", "titleEn": "SURMOUNT-4 post hoc: weight regain and cardiometabolic health", "firstAuthor": "Horn DB", "journal": "JAMA Internal Medicine", "year": 2026, "doi": "10.1001/jamainternmed.2025.6112", "url": "https://doi.org/10.1001/jamainternmed.2025.6112", "registryId": "NCT04660643", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "308 participantes de SURMOUNT-4 que perdieron al menos un 10 % del peso en las 36 semanas iniciales con tirzepatida y fueron aleatorizados a placebo (71,1 % mujeres, edad media de 47,1 años).", "populationEn": "308 SURMOUNT-4 participants who lost at least 10% of their weight during the first 36 weeks on tirzepatide and were randomized to placebo (71.1% women, mean age 47.1 years).", "nParticipants": 308, "durationWeeks": 88, "primaryOutcomeEs": "Cambios de los parámetros cardiometabólicos entre la semana 36 y la 88 según la proporción del peso perdido que se recuperó tras retirar la tirzepatida (menos del 25 %, del 25 al 50 %, del 50 al 75 % y 75 % o más).", "primaryOutcomeEn": "Changes in cardiometabolic parameters between week 36 and week 88 according to the share of lost weight regained after tirzepatide was withdrawn (less than 25%, 25 to 50%, 50 to 75% and 75% or more).", "resultSummaryEs": "Tras pasar de tirzepatida a placebo, cuanto más peso se recuperó entre la semana 36 y la 88, más empeoraron los parámetros cardiometabólicos: el perímetro de cintura aumentó 0,8 cm (IC 95 %: −1,0 a 2,6) en quienes recuperaron menos del 25 % del peso perdido y 14,7 cm (IC 95 %: 12,7 a 16,7) en quienes recuperaron el 75 % o más. De los 308 participantes, 54 recuperaron menos del 25 %, 77 entre el 25 y el 50 %, 103 entre el 50 y el 75 % y 74 el 75 % o más. La presión arterial sistólica subió en todos los grupos, de 6,8 mm Hg (IC 95 %: 3,9 a 9,7) en el de menor recuperación a 10,4 mm Hg (IC 95 %: 8,0 a 12,8) en el de mayor, y la HbA1c de 0,14 a 0,35 puntos. En quienes recuperaron menos del 25 %, la cintura, el colesterol no HDL y la insulina en ayunas no cambiaron de forma significativa respecto a la semana 36.", "resultSummaryEn": "After switching from tirzepatide to placebo, the more weight people regained between week 36 and week 88, the more their cardiometabolic parameters worsened: waist circumference increased by 0.8 cm (95% CI, −1.0 to 2.6) in those who regained less than 25% of the weight lost and by 14.7 cm (95% CI, 12.7 to 16.7) in those who regained 75% or more. Of the 308 participants, 54 regained less than 25%, 77 between 25 and 50%, 103 between 50 and 75% and 74 regained 75% or more. Systolic blood pressure rose in all groups, from 6.8 mm Hg (95% CI, 3.9 to 9.7) in the lowest-regain group to 10.4 mm Hg (95% CI, 8.0 to 12.8) in the highest, and HbA1c rose by 0.14 to 0.35 points. In those who regained less than 25%, waist circumference, non-HDL cholesterol and fasting insulin did not change significantly from week 36.", "limitationsEs": "Financiado por Eli Lilly, con varios autores empleados de la compañía. Análisis post hoc: las categorías de recuperación no fueron aleatorizadas y no permiten atribuir causalidad. Solo incluye a quienes perdieron al menos un 10 % y excluyó a personas con diabetes.", "limitationsEn": "Funded by Eli Lilly, with several authors employed by the company. Post hoc analysis: the regain categories were not randomized and do not allow conclusions about cause and effect. It only includes people who lost at least 10% and excluded people with diabetes.", "sources": [ { "title": "Horn DB, et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Intern Med. 2026;186(2):157-167", "url": "https://doi.org/10.1001/jamainternmed.2025.6112", "publisher": "JAMA Internal Medicine", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 41284285 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/41284285/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" }, { "title": "Full text PMC12645400 (funding)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12645400/", "publisher": "PubMed Central (National Library of Medicine)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "SURMOUNT-4 (análisis post hoc)", "pageUrl": "https://saciedad.com/estudios/surmount-4-cardiometabolico-post-hoc/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-4-cardiometabolico-post-hoc/" }, { "id": "surmount-maintain", "acronym": "SURMOUNT-MAINTAIN", "title": "Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial", "titleEn": "SURMOUNT-MAINTAIN: keeping weight off on tirzepatide", "firstAuthor": "Horn DB", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)00656-2", "url": "https://doi.org/10.1016/S0140-6736(26)00656-2", "registryId": "NCT06047548", "drugIds": [ "tirzepatida" ], "design": "rct", "populationEs": "441 adultos con obesidad (IMC de 30 o más, o de 27 o más con al menos una complicación relacionada con el peso) y sin diabetes (según el registro) empezaron 60 semanas de tirzepatida abierta a la dosis máxima tolerada (10 o 15 mg) en 20 centros de Estados Unidos; 378 se aleatorizaron después a seguir con esa dosis (140), bajar a 5 mg (144) o pasar a placebo (94). Al inicio, 65 % mujeres, edad media de 46,6 años, peso medio de 113,8 kg e IMC medio de 40,1.", "populationEn": "441 adults with obesity (BMI of 30 or more, or 27 or more with at least one weight-related complication) and without diabetes (per the registry) started 60 weeks of open-label tirzepatide at the maximum tolerated dose (10 or 15 mg) at 20 sites in the United States; 378 were then randomized to stay on that dose (140), step down to 5 mg (144) or switch to placebo (94). At baseline, 65% were women, mean age was 46.6 years, mean weight 113.8 kg and mean BMI 40.1.", "nParticipants": 378, "durationWeeks": 112, "primaryOutcomeEs": "Cambio porcentual del peso desde el inicio del estudio hasta la semana 112 (52 semanas después de la aleatorización) al seguir con la dosis máxima tolerada de tirzepatida o bajar a 5 mg semanales, frente a pasar a placebo. Desde la semana 84 podía recibir tirzepatida de rescate quien recuperaba más del 50 % del peso perdido.", "primaryOutcomeEn": "Percentage change in weight from the start of the study to week 112 (52 weeks after randomization) when staying on the maximum tolerated dose of tirzepatide or stepping down to 5 mg once weekly, versus switching to placebo. From week 84, participants who regained more than 50% of the weight they had lost could receive rescue tirzepatide.", "resultSummaryEs": "En la semana 112, el peso había cambiado un −21,9 % con la dosis máxima tolerada de tirzepatida, un −16,6 % con 5 mg y un −9,9 % con placebo; las diferencias frente a placebo fueron de −12,0 puntos porcentuales (IC 95 %: −13,8 a −10,1) y de −6,6 puntos (IC 95 %: −8,3 a −5,0), ambas con p < 0,0001. Las cifras se miden desde el peso anterior a la tirzepatida, así que incluyen lo perdido en las 60 semanas previas a la aleatorización. De los participantes aleatorizados, el 91 % terminó el estudio. Los efectos adversos más frecuentes con tirzepatida fueron digestivos, en su mayoría leves o moderados y concentrados en la fase de aumento de dosis.", "resultSummaryEn": "At week 112, weight had changed by −21.9% on the maximum tolerated dose of tirzepatide, −16.6% on 5 mg and −9.9% on placebo; the differences versus placebo were −12.0 percentage points (95% CI, −13.8 to −10.1) and −6.6 points (95% CI, −8.3 to −5.0), both p < 0.0001. The figures are measured from the weight before tirzepatide, so they include what was lost in the 60 weeks before randomization. Of the randomized participants, 91% completed the study. The most common adverse effects on tirzepatide were digestive, mostly mild or moderate and concentrated in the dose-escalation phase.", "limitationsEs": "Financiado por Eli Lilly, fabricante de la tirzepatida. Solo se aleatorizó a quienes completaron y toleraron 60 semanas a dosis máxima, todos en Estados Unidos, lo que puede sobrestimar el mantenimiento en la práctica. La fase aleatorizada duró 52 semanas, y el rescate con tirzepatida permitido desde la semana 84 complica la comparación entre grupos. The Lancet publicó una corrección (el denominador del rescate en el grupo placebo y una figura) que no cambia las cifras citadas aquí.", "limitationsEn": "Funded by Eli Lilly, which makes tirzepatide. Only people who completed and tolerated 60 weeks at the maximum dose were randomized, all in the United States, which may overstate maintenance in practice. The randomized phase lasted 52 weeks, and the rescue tirzepatide allowed from week 84 complicates the comparison between groups. The Lancet published a correction (the placebo denominator for rescue use and one figure) that does not change the figures cited here.", "sources": [ { "title": "Horn DB, et al. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN). Lancet. 2026;407(10545):2305-2318", "url": "https://doi.org/10.1016/S0140-6736(26)00656-2", "publisher": "The Lancet", "accessed": "2026-09-24" }, { "title": "PubMed record PMID 42119587 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42119587/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-24" }, { "title": "Department of Error. Lancet. 2026;407(10545):2290 (correction to SURMOUNT-MAINTAIN)", "url": "https://doi.org/10.1016/S0140-6736(26)01134-7", "publisher": "The Lancet", "accessed": "2026-09-24" }, { "title": "ClinicalTrials.gov record NCT06047548 (registration, eligibility and sites)", "url": "https://clinicaltrials.gov/study/NCT06047548", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-09-24" } ], "lastReviewed": "2026-09-24", "name": "SURMOUNT-MAINTAIN", "pageUrl": "https://saciedad.com/estudios/surmount-maintain/", "pageUrlEn": "https://saciedad.com/en/studies/surmount-maintain/" }, { "id": "transcend-t2d-1", "acronym": "TRANSCEND-T2D-1", "title": "Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial", "titleEn": "TRANSCEND-T2D-1: retatrutide in type 2 diabetes", "firstAuthor": "Bajaj HS", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)00967-0", "url": "https://doi.org/10.1016/S0140-6736(26)00967-0", "registryId": "NCT06354660", "drugIds": [ "retatrutida" ], "design": "rct", "populationEs": "537 adultos con diabetes tipo 2 no controlada solo con dieta y ejercicio (HbA1c del 7,0 al 9,5 % e IMC de 23 o más), en 48 centros de Estados Unidos, México e India; 55 % mujeres, edad media de 48,8 años, HbA1c media de 7,9 %, 2,5 años de diabetes de media e IMC medio de 35,8.", "populationEn": "537 adults with type 2 diabetes not controlled with diet and exercise alone (HbA1c of 7.0 to 9.5% and BMI of 23 or more), at 48 sites in the United States, Mexico and India; 55% women, mean age 48.8 years, mean HbA1c 7.9%, an average of 2.5 years with diabetes and mean BMI 35.8.", "nParticipants": 537, "durationWeeks": 40, "primaryOutcomeEs": "Cambio de la HbA1c desde el inicio hasta la semana 40 con retatrutida 4, 9 o 12 mg semanales frente a placebo; el cambio porcentual del peso fue un objetivo secundario clave.", "primaryOutcomeEn": "Change in HbA1c from baseline to week 40 with retatrutide 4, 9 or 12 mg once weekly versus placebo; percentage change in weight was a key secondary objective.", "resultSummaryEs": "A las 40 semanas, la HbA1c bajó 1,69, 1,86 y 1,94 puntos con retatrutida 4, 9 y 12 mg, frente a 0,81 con placebo; las diferencias fueron de −0,88 (IC 95 %: −1,18 a −0,59), −1,04 (IC 95 %: −1,32 a −0,76) y −1,12 puntos (IC 95 %: −1,39 a −0,85). El peso cambió un −11,5 %, un −13,9 % y un −15,3 % con las tres dosis, frente al −2,6 % con placebo. Los efectos adversos más frecuentes fueron digestivos, en general leves o moderados y decrecientes con el tiempo; abandonó el tratamiento por efectos adversos entre el 2 y el 5 % con retatrutida, frente a nadie con placebo. No hubo hipoglucemias graves.", "resultSummaryEn": "At 40 weeks, HbA1c fell by 1.69, 1.86 and 1.94 points with retatrutide 4, 9 and 12 mg, compared with 0.81 on placebo; the differences were −0.88 (95% CI, −1.18 to −0.59), −1.04 (95% CI, −1.32 to −0.76) and −1.12 points (95% CI, −1.39 to −0.85). Weight changed by −11.5%, −13.9% and −15.3% with the three doses, compared with −2.6% on placebo. The most common adverse effects were digestive, generally mild or moderate and decreasing over time; between 2 and 5% of participants on retatrutide stopped treatment because of adverse effects, compared with none on placebo. There was no severe hypoglycemia.", "limitationsEs": "Financiado por Eli Lilly, que desarrolla la retatrutida. Duró 40 semanas e incluyó solo a personas con diabetes tipo 2 de corta evolución que no tomaban otros fármacos para la diabetes. Se comparó con placebo, no con otros tratamientos. La retatrutida es un fármaco en investigación.", "limitationsEn": "Funded by Eli Lilly, which is developing retatrutide. It lasted 40 weeks and included only people with short-duration type 2 diabetes who were not taking other diabetes drugs. It was compared with placebo, not with other treatments. Retatrutide is an investigational drug.", "sources": [ { "title": "Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1). Lancet. 2026;407(10546):2402-2413", "url": "https://doi.org/10.1016/S0140-6736(26)00967-0", "publisher": "The Lancet", "accessed": "2026-09-23" }, { "title": "PubMed record PMID 42250575 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42250575/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-09-23" } ], "lastReviewed": "2026-09-23", "name": "TRANSCEND-T2D-1", "pageUrl": "https://saciedad.com/estudios/transcend-t2d-1/", "pageUrlEn": "https://saciedad.com/en/studies/transcend-t2d-1/" }, { "id": "triumph-1", "acronym": "TRIUMPH-1", "title": "Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity", "titleEn": "TRIUMPH-1: retatrutide for obesity without diabetes", "firstAuthor": "Jastreboff AM", "journal": "New England Journal of Medicine", "year": 2026, "doi": "10.1056/NEJMoa2604169", "url": "https://doi.org/10.1056/NEJMoa2604169", "registryId": "NCT05929066", "drugIds": [ "retatrutida" ], "design": "rct", "populationEs": "2339 adultos con obesidad y sin diabetes (según el registro, IMC de 30 o más, o de 27 o más con hipertensión, dislipemia, apnea obstructiva del sueño o enfermedad cardiovascular). Dentro del ensayo había un subgrupo de 574 participantes con artrosis de rodilla y otro de 243 con apnea obstructiva del sueño. El registro de ClinicalTrials.gov da 2335 participantes.", "populationEn": "2,339 adults with obesity and without diabetes (per the registry, a BMI of 30 or more, or 27 or more with high blood pressure, abnormal blood lipids, obstructive sleep apnea or cardiovascular disease). The trial included a subgroup of 574 participants with knee osteoarthritis and another of 243 with obstructive sleep apnea. The ClinicalTrials.gov registry lists 2,335 participants.", "nParticipants": 2339, "durationWeeks": 80, "primaryOutcomeEs": "Cambio porcentual del peso a las 80 semanas con retatrutida 9 y 12 mg semanales frente a placebo (también se estudió la dosis de 4 mg); en el subgrupo con artrosis de rodilla, el cambio del dolor en la escala WOMAC, y en el subgrupo con apnea obstructiva del sueño, el cambio del índice de apnea-hipopnea.", "primaryOutcomeEn": "Percentage change in weight at 80 weeks with retatrutide 9 and 12 mg once weekly versus placebo (a 4 mg dose was also studied); in the knee osteoarthritis subgroup, the change in WOMAC pain score, and in the obstructive sleep apnea subgroup, the change in the apnea-hypopnea index.", "resultSummaryEs": "A las 80 semanas, el peso cambió un −17,6 %, un −23,7 % y un −25,0 % con retatrutida 4, 9 y 12 mg, frente al −3,9 % con placebo, con el estimando de régimen de tratamiento (intención de tratar); las diferencias frente a placebo fueron de −19,8 y −21,0 puntos porcentuales con 9 y 12 mg (p < 0,001). En el subgrupo con artrosis de rodilla, el dolor en la escala WOMAC bajó 3,4, 3,9 y 4,1 puntos con las tres dosis, frente a 2,5 con placebo (intención de tratar); con el estimando híbrido del análisis principal, las diferencias con 9 y 12 mg fueron de −1,6 y −1,8 puntos. En el subgrupo con apnea obstructiva del sueño, el índice de apnea-hipopnea bajó 22,8, 34,3 y 32,1 eventos por hora, frente a 9,6 con placebo (intención de tratar); con el estimando híbrido, las diferencias con 9 y 12 mg fueron de −24,4 y −21,9 eventos por hora. Los efectos adversos más frecuentes fueron digestivos; el resumen del artículo no da su frecuencia ni intervalos de confianza.", "resultSummaryEn": "At 80 weeks, weight changed by −17.6%, −23.7% and −25.0% with retatrutide 4, 9 and 12 mg, compared with −3.9% on placebo, using the treatment-regimen estimand (intention to treat); the differences versus placebo were −19.8 and −21.0 percentage points with 9 and 12 mg (p < 0.001). In the knee osteoarthritis subgroup, WOMAC pain fell by 3.4, 3.9 and 4.1 points with the three doses, compared with 2.5 on placebo (intention to treat); with the hybrid estimand of the main analysis, the differences with 9 and 12 mg were −1.6 and −1.8 points. In the obstructive sleep apnea subgroup, the apnea-hypopnea index fell by 22.8, 34.3 and 32.1 events per hour, compared with 9.6 on placebo (intention to treat); with the hybrid estimand, the differences with 9 and 12 mg were −24.4 and −21.9 events per hour. The most common adverse effects were digestive; the paper’s abstract does not give their frequency or confidence intervals.", "limitationsEs": "Financiado por Eli Lilly, que desarrolla la retatrutida. El resumen del artículo no da los abandonos por efectos adversos ni la frecuencia de cada efecto adverso, entre ellos la disestesia; las cifras de la nota de prensa de Lilly usan otro estimando (el de eficacia) y no son comparables con estas. Se comparó con placebo, no con otros tratamientos. La retatrutida es un fármaco en investigación, no aprobado en ningún país.", "limitationsEn": "Funded by Eli Lilly, which is developing retatrutide. The paper’s abstract does not give discontinuations due to adverse effects or the frequency of each adverse effect, dysesthesia included; the figures in Lilly’s press release use a different estimand (the efficacy estimand) and are not comparable with these. It was compared with placebo, not with other treatments. Retatrutide is an investigational drug, not approved in any country.", "sources": [ { "title": "Jastreboff AM, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). N Engl J Med. Published online September 29, 2026", "url": "https://doi.org/10.1056/NEJMoa2604169", "publisher": "New England Journal of Medicine", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42814954 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42814954/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT05929066 (TRIUMPH-1: registration, eligibility and enrollment)", "url": "https://clinicaltrials.gov/study/NCT05929066", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "TRIUMPH-1", "pageUrl": "https://saciedad.com/estudios/triumph-1/", "pageUrlEn": "https://saciedad.com/en/studies/triumph-1/" }, { "id": "triumph-2", "acronym": "TRIUMPH-2", "title": "Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial", "titleEn": "TRIUMPH-2: retatrutide for obesity with type 2 diabetes", "firstAuthor": "Bellido V", "journal": "The Lancet", "year": 2026, "doi": "10.1016/S0140-6736(26)01861-1", "url": "https://doi.org/10.1016/S0140-6736(26)01861-1", "registryId": "NCT05929079", "drugIds": [ "retatrutida" ], "design": "rct", "populationEs": "1152 adultos con diabetes tipo 2 (HbA1c del 6,5 al 10,5 %) e IMC de 27 o más, tratados solo con dieta y ejercicio o con hasta tres antidiabéticos orales, en 92 centros de ocho países; 48 % mujeres, edad media de 55,1 años, IMC medio de 38,2 y HbA1c media del 7,71 %. El 92 % tomaba algún antidiabético oral.", "populationEn": "1,152 adults with type 2 diabetes (HbA1c of 6.5 to 10.5%) and a BMI of 27 or more, managed with diet and exercise alone or with up to three oral diabetes drugs, at 92 sites in eight countries; 48% women, mean age 55.1 years, mean BMI 38.2 and mean HbA1c 7.71%. 92% were taking an oral diabetes drug.", "nParticipants": 1152, "durationWeeks": 80, "primaryOutcomeEs": "Cambio porcentual del peso desde el inicio hasta la semana 80 con retatrutida 9 y 12 mg semanales frente a placebo; la comparación de la dosis de 4 mg con placebo fue un objetivo secundario clave.", "primaryOutcomeEn": "Percentage change in weight from baseline to week 80 with retatrutide 9 and 12 mg once weekly versus placebo; the comparison of the 4 mg dose with placebo was a key secondary objective.", "resultSummaryEs": "A las 80 semanas, el peso cambió un −11,9 %, un −16,8 % y un −18,8 % con retatrutida 4, 9 y 12 mg, frente al −5,1 % con placebo, con el estimando de régimen de tratamiento; las diferencias fueron de −6,9 (IC 95 %: −8,7 a −5,1), −11,8 (IC 95 %: −13,7 a −9,8) y −13,8 puntos porcentuales (IC 95 %: −15,8 a −11,8), todas con p < 0,0001. Completó el tratamiento el 84 % de los participantes. Los efectos adversos más frecuentes fueron digestivos: tuvo diarrea el 27, el 34 y el 34 % con las tres dosis, frente al 13 % con placebo, y náuseas el 14, el 21 y el 28 %, frente al 8 %; la hipotensión (1, 5 y 6 %, frente a menos del 1 %) y la disestesia (4, 6 y 7 %, frente al 1 %) también fueron más frecuentes con retatrutida. Dejó el tratamiento por efectos adversos o por muerte el 4, el 12 y el 8 % con 4, 9 y 12 mg, frente al 5 % con placebo; hubo seis muertes con retatrutida y una con placebo, ninguna relacionada con el tratamiento según el investigador.", "resultSummaryEn": "At 80 weeks, weight changed by −11.9%, −16.8% and −18.8% with retatrutide 4, 9 and 12 mg, compared with −5.1% on placebo, using the treatment-regimen estimand; the differences were −6.9 (95% CI, −8.7 to −5.1), −11.8 (95% CI, −13.7 to −9.8) and −13.8 percentage points (95% CI, −15.8 to −11.8), all p < 0.0001. 84% of participants completed treatment. The most common adverse effects were digestive: diarrhea affected 27%, 34% and 34% with the three doses, compared with 13% on placebo, and nausea 14%, 21% and 28%, compared with 8%; hypotension (1%, 5% and 6%, compared with less than 1%) and dysesthesia (4%, 6% and 7%, compared with 1%) were also more common with retatrutide. 4%, 12% and 8% stopped treatment because of adverse effects or death with 4, 9 and 12 mg, compared with 5% on placebo; there were six deaths on retatrutide and one on placebo, none related to treatment according to the investigator.", "limitationsEs": "Financiado por Eli Lilly, que desarrolla la retatrutida. El resumen del artículo dice que mejoró el control de la glucosa, pero no da la cifra de HbA1c. Se comparó con placebo, no con otros tratamientos. La retatrutida es un fármaco en investigación, no aprobado en ningún país.", "limitationsEn": "Funded by Eli Lilly, which is developing retatrutide. The paper’s abstract says blood sugar control improved but does not give the HbA1c figure. It was compared with placebo, not with other treatments. Retatrutide is an investigational drug, not approved in any country.", "sources": [ { "title": "Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. Published online September 29, 2026", "url": "https://doi.org/10.1016/S0140-6736(26)01861-1", "publisher": "The Lancet", "accessed": "2026-10-05" }, { "title": "PubMed record PMID 42810372 (abstract)", "url": "https://pubmed.ncbi.nlm.nih.gov/42810372/", "publisher": "National Library of Medicine (PubMed)", "accessed": "2026-10-05" }, { "title": "ClinicalTrials.gov record NCT05929079 (TRIUMPH-2: registration and eligibility)", "url": "https://clinicaltrials.gov/study/NCT05929079", "publisher": "ClinicalTrials.gov (National Library of Medicine)", "accessed": "2026-10-05" } ], "lastReviewed": "2026-10-05", "name": "TRIUMPH-2", "pageUrl": "https://saciedad.com/estudios/triumph-2/", "pageUrlEn": "https://saciedad.com/en/studies/triumph-2/" } ] }