orforglipron · 40 weeks
ACHIEVE-2
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.
Randomized controlled trial
ACHIEVE-5: orforglipron added to insulin glargine in T2D
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.
Giorgino F et al. Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. JAMA, 2026. DOI: 10.1001/jama.2026.9512
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- Alex Gonzalez
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Key facts
- Drug
- orforglipron
- Design
- Randomized controlled trial
- Participants
- 546
- Duration
- 40 weeks
- Funding
- Eli Lilly
- Registry
- NCT06109311
- Population
- 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.
- Primary outcome
- 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.
What it found
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.
Limitations
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.
What it means for you
In people with type 2 diabetes already using insulin glargine, adding orforglipron tablets lowered HbA1c by about one point more than placebo on 12 and 36 mg over 40 weeks, without increasing significant hypoglycemia. This is a blood sugar result from a trial funded by the manufacturer, and in the US orforglipron (Foundayo) is approved for weight management only. If you use insulin, any change to your treatment is your doctor’s decision.
Further reading
Sources
The original paper and the records consulted for this summary, with the date they were accessed.
- JAMA (American Medical Association).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.accessed .
- National Library of Medicine (PubMed).PubMed record PMID 42251769 (abstract).accessed .
- ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT06109311 (ACHIEVE-5: registration, sponsor and masking).accessed .