Eli Lilly announces orforglipron met primary endpoint in ACHIEVE-2, ACHIEVE-5

Eli Lilly (LLY) announced topline results from the Phase 3 ACHIEVE-2 and ACHIEVE-5 trials. ACHIEVE-2, the second head-to-head trial in the program, evaluated orforglipron versus dapagliflozin, an SGLT-2 inhibitor, in adults with type 2 diabetes inadequately controlled on metformin. Separately, ACHIEVE-5 assessed orforglipron versus placebo in adults with type 2 diabetes and inadequate glycemic control with titrated insulin glargine, with or without metformin and/or SGLT-2 inhibitors. In both trials, orforglipron met the primary and all key secondary endpoints at 40 weeks for both the efficacy and treatment-regimen estimands, delivering significant A1C reduction and weight loss as well as improvements in multiple cardiovascular risk factors, all consistent with previously disclosed studies in type 2 diabetes. In both trials, the overall safety and tolerability profile of orforglipron, as well as treatment discontinuation rates, were consistent with previous studies. The most common adverse events were gastrointestinal-related and generally mild-to-moderate in severity. No hepatic safety signal was observed. The detailed results of these trials will be presented at a future medical meeting and published in a peer-reviewed journal. Results are expected in the first quarter of 2026 for ACHIEVE-4, the final global registration trial in the ACHIEVE program. Lilly plans to submit orforglipron for the treatment of type 2 diabetes to global regulatory agencies in 2026, while submission for the treatment of obesity is on track to occur by the end of this year.