Eli Lilly has announced positive topline results from ACHIEVE 4, the longest and largest Phase 3 study of its oral GLP 1 receptor agonist, Foundayo, to date. The trial evaluated the efficacy and safety of Foundayo against insulin glargine in over 2,700 adults with type 2 diabetes and obesity or overweight who were at increased cardiovascular risk. Foundayo met its primary objective by demonstrating non inferiority in the risk of major adverse cardiovascular events, which includes cardiovascular death, heart attack, stroke, or hospitalization for unstable chest pain.

Beyond cardiovascular safety, Foundayo demonstrated superior results in managing metabolic health markers compared to insulin glargine. At the 52 week mark, patients on Foundayo saw an A1C reduction of 1.6% compared to 1.0% for the insulin group. Weight loss results were even more pronounced, with Foundayo patients losing 8.8% of their body weight while those on insulin glargine saw a weight gain of 1.7%. These improvements remained consistent through 104 weeks of therapy.

A pre planned analysis of the trial data revealed a striking 57% lower risk of all cause death for patients taking Foundayo compared to those on insulin glargine. While this specific metric was not controlled for multiplicity, it suggests a potential for comprehensive health benefits beyond simple glucose management. Foundayo also showed meaningful improvements from baseline across several cardiovascular risk factors, including non HDL cholesterol, systolic blood pressure, triglycerides, and hsCRP.

Clinical and strategic commentary

Thomas Seck, M.D., senior vice president of product development at Lilly Cardiometabolic Health, emphasized the clinical impact of these results:

“Across seven Phase 3 studies enrolling more than 11,000 patients, Foundayo has demonstrated a consistent safety and efficacy profile. ACHIEVE-4 adds a new dimension to that evidence — cardiovascular safety and a lower observed risk of all-cause death in patients who carry elevated cardiovascular risk. Together with the simplicity of a once-daily pill that requires no food or water restrictions, we believe Foundayo could be an important new treatment option for people with type 2 diabetes.”

Safety and regulatory path forward

The safety profile of Foundayo in ACHIEVE 4 was generally consistent with previous trials and the broader GLP 1 class. The most common adverse events reported were nausea, vomiting, diarrhea, decreased appetite, and constipation. A thorough analysis confirmed no hepatic safety signal or drug induced liver injury, maintaining consistency with all prior studies in the ACHIEVE and ATTAIN programs.

Lilly plans to submit Foundayo to the U.S. Food and Drug Administration for the treatment of type 2 diabetes by the end of the second quarter of 2026 under the Commissioner’s National Priority Review Voucher.