orforglipron and semaglutide · 52 weeks
ACHIEVE-3
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.
Randomized controlled trial
ACHIEVE-2: orforglipron vs dapagliflozin in type 2 diabetes
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.
Welch M et al. 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. The Lancet, 2026. DOI: 10.1016/S0140-6736(26)00800-7
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- Alex Gonzalez
- Last updated
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Key facts
- Drug
- orforglipron
- Design
- Randomized controlled trial
- Participants
- 962
- Duration
- 40 weeks
- Funding
- Eli Lilly
- Registry
- NCT06192108
- Population
- 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.
- Primary outcome
- 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.
What it found
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.
Limitations
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.
What it means for you
In type 2 diabetes not controlled on metformin, orforglipron tablets lowered HbA1c more than dapagliflozin (Farxiga) at 40 weeks with all three doses studied, but caused more digestive side effects and more dropouts. This is a result on blood sugar control: the published abstract does not report the change in weight, and it was an open-label trial funded by the maker of orforglipron. Your doctor can tell you whether it is authorized where you live and whether it makes sense for your treatment.
Further reading
Sources
The original paper and the records consulted for this summary, with the date they were accessed.
- The Lancet.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.accessed .
- National Library of Medicine (PubMed).PubMed record PMID 42259339 (abstract).accessed .
- ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT06192108 (registration and participating countries).accessed .