- Orforglipron 36 mg lowered A1C by 2.2% vs. 1.4% with semaglutide 14 mg.
- Participants on orforglipron 36 mg lost 19.7 lbs compared to 11.0 lbs with semaglutide.
- Lilly submitted orforglipron to regulators in over 40 countries.
- Potential U.S. action for obesity expected in Q2 2026.
Trial Overview
Eli Lilly's ACHIEVE-3 trial compared the efficacy and safety of orforglipron, a small molecule oral GLP-1, with oral semaglutide in adults with type 2 diabetes inadequately controlled with metformin. The 52-week study involved 1,698 participants across four treatment arms: orforglipron 12 mg and 36 mg, and oral semaglutide 7 mg and 14 mg.
Key Findings
Orforglipron 36 mg demonstrated superior results, lowering A1C by 2.2% compared to 1.4% with semaglutide 14 mg. In terms of weight loss, participants on orforglipron 36 mg lost 19.7 lbs (9.2%), while those on semaglutide lost 11.0 lbs (5.3%). These results indicate a 73.6% greater relative weight loss with orforglipron.
Regulatory Submissions
Lilly has submitted orforglipron to regulators in over 40 countries, with potential U.S. regulatory action for obesity anticipated in the second quarter of 2026.
Research Implications
The trial provides the first head-to-head comparison of two oral GLP-1 receptor agonist therapies in type 2 diabetes, with orforglipron showing clinically meaningful differences. Improvements in A1C and weight were observed as early as four weeks and sustained throughout the study.
