INDIANAPOLIS (dpa-AFX) - Eli Lilly and Co. (LLY) announced Wednesday positive topline results from ACHIEVE-3, an open-label randomized Phase 3 clinical trial evaluating the safety and efficacy of orforglipron compared to oral semaglutide, administered according to approved label instructions, in 1,698 adults with type 2 diabetes inadequately controlled with metformin.
The 52-week trial compared orforglipron (12 mg and 36 mg) to oral semaglutide (7 mg and 14 mg) across four active treatment arms to assess glycemic control and weight loss.
At 52 weeks, orforglipron met the primary and all key secondary endpoints across each dose comparison vs oral semaglutide, delivering greater improvements in A1C and weight.
In the ACHIEVE-3 trial, orforglipron met the primary endpoint and showed superiority vs oral semaglutide, lowering A1C by an average of 1.9% (12 mg) and 2.2% (36 mg) compared to 1.1% (7 mg) and 1.4% (14 mg) with oral semaglutide at 52 weeks using the efficacy estimand.
In a secondary endpoint, 37.1% of participants taking the highest dose of orforglipron achieved an A1C <5.7% compared to 12.5% taking the highest dose of oral semaglutide.
In key secondary endpoints, orforglipron was also superior to oral semaglutide for weight loss, and participants taking orforglipron lost an average of 14.6 lbs (6.7%; 12 mg) and 19.7 lbs (9.2%; 36 mg) compared to 7.9 lbs (3.7%; 7 mg) and 11.0 lbs (5.3%; 14 mg) with oral semaglutide, a 73.6% greater relative weight loss at the highest dose comparison.
Orforglipron also showed clinically meaningful improvements across key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure and triglycerides
The overall safety and tolerability profile of orforglipron in ACHIEVE-3 was consistent with previous trials. However, the study was not powered to compare the safety and tolerability of orforglipron and oral semaglutide. No hepatic safety signal was observed for orforglipron.
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