On April 18, 2026, Eli Lilly and Company announced the formal completion of ACHIEVE-4, a pivotal Phase 3 clinical trial evaluating orforglipron, its investigational once-daily oral non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist. The study compared the efficacy and safety of orforglipron against injectable insulin glargine in adults with type 2 diabetes and obesity or overweight who are at increased cardiovascular risk.
The ACHIEVE-4 trial enrolled more than 2,700 participants across 15 countries, making it the largest and longest study of orforglipron in the type 2 diabetes population to date. According to official data released by the company, the trial met its primary endpoint by demonstrating a non-inferior risk of major adverse cardiovascular events (MACE-4), which includes cardiovascular death, heart attack, stroke, and hospitalization for unstable chest pain. Specifically, orforglipron showed a 16% lower risk of MACE-4 and a 23% lower risk of MACE-3 compared to the insulin glargine group.
A notable finding in the study was a 57% lower risk of all-cause death among participants treated with orforglipron compared to those receiving insulin glargine. While this specific metric was not controlled for multiplicity in the trial design, the company highlighted it as a significant indicator of the drug's potential health benefits. Thomas Seck, M.D., Senior Vice President of Product Development at Lilly Cardiometabolic Health, stated that the ACHIEVE-4 results add a critical dimension of cardiovascular safety to the existing evidence for orforglipron across the broader clinical program.
Orforglipron, which the company has referred to by the brand name Foundayo in recent communications, represents a shift in GLP-1 therapy. Unlike existing oral peptide-based GLP-1 medications that require strict fasting and water-intake protocols, orforglipron is a small-molecule drug that can be taken at any time of day without food or water restrictions. This chemical structure also allows for large-scale manufacturing through chemical synthesis, which the company indicates will help bypass the supply constraints that have impacted injectable incretin therapies.
The completion of ACHIEVE-4 follows the successful readout of other trials in the orforglipron development program, including the ATTAIN-1 study for obesity, which reported a 12.4% mean weight loss at 72 weeks in late 2025. With the ACHIEVE-4 data finalized, Eli Lilly confirmed its intention to submit a New Drug Application for the treatment of type 2 diabetes to the U.S. Food and Drug Administration by the end of the second quarter of 2026. The company had previously initiated regulatory submissions for the obesity indication in late 2025.