Lilly’s Oral GLP-1 Foundayo Meets Cardiovascular Safety Endpoints

Eli Lilly’s oral GLP-1 drug, Foundayo (orforglipron), met primary cardiovascular safety endpoints in the Phase 3 ACHIEVE-4 clinical trial. It demonstrated non-inferiority to insulin glargine while reducing A1C levels and body weight.

The findings, detailed in a company release, suggest the small-molecule drug could serve as a treatment option for patients with type 2 diabetes.

"For people living with type 2 diabetes, protecting the heart is as important as controlling blood sugar," said Klara Klein, M.D., Ph.D., Assistant Professor of Medicine, University of North Carolina School of Medicine.

Clinical Trial Data and Outcomes

The ACHIEVE-4 trial evaluated Foundayo against insulin glargine, a long-acting basal insulin. According to the study results, participants treated with Foundayo experienced a 16% lower risk of MACE-4 (a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization) compared to those on insulin glargine. The risk of MACE-3, which excludes revascularization, was 23% lower.

Pre-planned exploratory analyses indicated a 53% lower risk of cardiovascular death and a 57% lower risk of all-cause death in the Foundayo group compared to the insulin glargine cohort.

"Foundayo has consistently delivered strong efficacy in type 2 diabetes across our Phase 3 ACHIEVE program," said Thomas Seck, M.D., senior vice president of product development, Lilly Cardiometabolic Health.

Mechanism and Administration

Unlike injectable GLP-1 receptor agonists, Foundayo is a once-daily, non-peptide small molecule. Its chemical structure allows for oral administration without the timing requirements regarding food or beverage consumption that complicate the use of other oral medications.

Why This Matters for Diabetes Care

The ability to manage both glycemic control and cardiovascular risk through an oral treatment changes care for a patient population that often requires multiple daily injections. By demonstrating cardiovascular safety in its largest and longest type 2 diabetes study to date, Lilly is positioning Foundayo to compete in the cardiometabolic market, where heart-health outcomes are a standard benchmark for drug efficacy in chronic metabolic diseases.