Eli Lilly and Company has announced positive 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 (3 mg, 12 mg, 36 mg) 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.
“Orforglipron has now demonstrated superiority over two active comparators in clinical trials for type 2 diabetes,” said Jeff Emmick, 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.”
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.
Orforglipron (or-for-GLIP-ron) is an investigational, once-daily small molecule (non-peptide) oral glucagon-like peptide-1 receptor agonist that can be taken any time of the day without restrictions on food and water intake. Orforglipron was discovered by Chugai Pharmaceutical and licensed by Lilly in 2018.
