Eli Lilly's orforglipron surpasses semaglutide in diabetes, weight loss trial

Chugai Pharmaceutical Co. announced positive topline results from Eli Lilly's ACHIEVE-3 trial for oral GLP-1 orforglipron, revealing its superiority over oral semaglutide in treating type 2 diabetes. Orforglipron, at its highest dose (36 mg), lowered HbA1c by 2.2% compared to 1.4% for oral semaglutide's highest dose (14 mg). Additionally, 37.1% of participants on the highest orforglipron dose achieved an A1C <5.7%, significantly higher than the 12.5% for semaglutide.

The trial also highlighted orforglipron's impact on weight loss. Participants on the highest dose of orforglipron lost an average of 19.7 lbs, representing a 9.2% reduction. This was a 73.6% greater relative weight loss compared to the highest dose of oral semaglutide, which resulted in an 11.0 lbs, 5.3% reduction. Clinically meaningful improvements were also observed across key cardiovascular risk factors.

The overall safety and tolerability profile of orforglipron aligned with previous trials, with gastrointestinal-related events being the most common adverse effects, generally mild-to-moderate. Eli Lilly expects to submit orforglipron for global regulatory approval in 2026.