Eli Lilly (NYSE:LLY) reached a landmark milestone in its metabolic health pipeline on April 16, 2026, announcing positive topline results from the Phase 3 ACHIEVE-4 clinical trial.
The study evaluated Foundayo (orforglipron), the company’s investigational once-daily oral non-peptide GLP-1 receptor agonist, in adults with type 2 diabetes and increased cardiovascular risk.
The trial successfully met its primary endpoint, demonstrating that Foundayo is non-inferior to insulin glargine regarding major adverse cardiovascular events (MACE-4), with a hazard ratio (HR) of 0.84.
Beyond cardiovascular safety, Foundayo showcased clinical superiority in several key metabolic areas at the 52-week mark.
Patients treated with Foundayo experienced significantly greater reductions in A1C levels and total body weight compared to those on insulin glargine.
The most striking data point emerged from a pre-planned secondary analysis, which revealed that Foundayo was associated with a 57% lower rate of all-cause mortality (HR 0.43; 95% CI 0.25–0.75) compared to the insulin glargine group.
While researchers noted the need for long-term follow-up to fully contextualize these findings, the mortality benefit represents a significant potential breakthrough for oral diabetes treatments.
Meanwhile, the safety profile of Foundayo was consistent with other GLP-1 receptor agonists, with gastrointestinal events being the most commonly reported side effects, typically occurring during the dose-escalation phase.
Based on these results, Eli Lilly remains on track to submit a New Drug Application (NDA) to the U.S. FDA for the treatment of type 2 diabetes by the end of the second quarter of 2026.
If approved, Foundayo would become the first non-peptide oral GLP-1 agonist on the market, offering a more convenient alternative to the current injectable standard of care.