Lilly to Seek FDA Approval for Foundayo in Diabetes

Eli Lilly says it will seek expanded FDA approval by the end of the quarter for its obesity drug Foundayo (orforglipron) as a treatment for diabetes, following positive topline results from its Phase 3 ACHIEVE-4 trial. The company said the oral GLP-1 receptor agonist met its primary cardiovascular safety endpoint while also demonstrating significant improvements in glycemic control, weight loss, and several cardiometabolic risk markers in adults with type 2 diabetes and elevated cardiovascular risk.

The ACHIEVE-4 study enrolled 2,749 participants across 15 countries and compared the therapy against insulin glargine in patients with Type 2 diabetes who also had obesity or were overweight with additional cardiovascular risk factors.

The trial met its primary objective of demonstrating non-inferiority for major adverse cardiovascular events (MACE-4), a composite endpoint that includes cardiovascular death, heart attack, stroke, and hospitalization for unstable angina. Foundayo showed a 16% lower risk of MACE-4 events compared with insulin glargine, satisfying the prespecified non-inferiority threshold, according to the company. A key secondary analysis also showed a 23% lower risk of MACE-3 events, which excludes unstable angina.

Lilly also said a pre-planned but non-multiplicity-controlled analysis found that patients receiving Foundayo experienced a 57% lower risk of all-cause death compared with insulin glargine. The company emphasized that this finding was exploratory but described it as a potentially meaningful signal in a high-risk population.

The company also reported improvements across multiple cardiovascular risk markers, including reductions in non-HDL cholesterol, systolic blood pressure, triglycerides, and high-sensitivity C-reactive protein (hsCRP), reinforcing a broader cardiometabolic benefit profile consistent with GLP-1 receptor agonism.

The positive data and plans to seek FDA approval come as Lilly has faced media scrutiny related to the drug after the agency released the approval letter, which outlined a postmarketing study requirement to further evaluate potential risks, including drug-induced liver injury and major adverse cardiovascular events.

The media attention appears to be an overreaction, according to financial analysts and industry observers, who noted that such postmarketing requirements are a standard feature of drug approvals rather than evidence of new or unexpected risk.

In response, Lilly said the agency’s requirements are “consistent with the standard approach to ongoing safety evaluation of newly approved medicines,” adding that no liver safety signals have emerged across its Phase 3 program.

Clinical data to date appear to support that view. In late-stage trials, isolated cases of elevated liver enzymes were observed but attributed to alternative causes rather than the drug itself, according to Barron’s. Additional data cited by BioPharma Dive show no increased rate of liver enzyme elevations compared with placebo or semaglutide.

Some analysts suggest the FDA’s request may be influenced by the drug’s development sequence. Unlike other GLP-1 therapies, Foundayo was approved first for obesity before completing longer-term outcomes trials typically required for diabetes indications, potentially prompting regulators to seek more robust follow-up data, BioPharma Dive reported.