Eli Lilly and Company reported positive topline results from its Phase 3 ACHIEVE-2 and ACHIEVE-5 trials, highlighting orforglipron’s potential as a foundational therapy for type 2 diabetes.
In ACHIEVE-2, a head-to-head trial, orforglipron was compared with the SGLT-2 inhibitor dapagliflozin in adults with type 2 diabetes inadequately controlled on metformin. ACHIEVE-5 evaluated orforglipron against placebo in adults with type 2 diabetes who had insufficient glycemic control on titrated insulin glargine, with or without metformin and/or SGLT-2 inhibitors.
"Orforglipron has now demonstrated superiority over two active comparators in clinical trials for type 2 diabetes," said Jeff Emmick, M.D., Ph.D., senior vice president of product development, Lilly Cardiometabolic Health. "In ACHIEVE-2, orforglipron outperformed dapagliflozin, a commonly used SGLT-2 therapy, and in ACHIEVE-3, showed greater efficacy than oral semaglutide. The findings from ACHIEVE-5 add to this momentum, showing significant A1C reduction and weight loss when used in combination with titrated basal insulin. Together, these results reinforce orforglipron's potential to become a new standard of care for people living with type 2 diabetes."
Across both trials, orforglipron (3 mg, 12 mg, 36 mg) met the primary and all key secondary endpoints at 40 weeks for efficacy and treatment-regimen estimands. Patients experienced meaningful reductions in A1C, weight loss, and improvements in multiple cardiovascular risk factors, consistent with earlier studies in type 2 diabetes.
Detailed trial results will be shared at a forthcoming medical meeting and in a peer-reviewed journal. ACHIEVE-4, the final global registration trial in the program, is expected to report results in Q1 2026. Lilly aims to submit orforglipron for type 2 diabetes treatment to global regulatory authorities in 2026, while regulatory submission for obesity treatment is on track by year-end.