Indianapolis – – September 30, 2026 -- Eli Lilly and Company (NYSE: LLY) reported that its oral GLP-1 therapy Foundayo (orforglipron) reduced cardiovascular death risk by 53% and all-cause death risk by 57% compared with insulin glargine in the Phase 3 ACHIEVE-4 trial, the largest and longest study of the medicine in type 2 diabetes to date.
Foundayo meets non-inferiority bar on major cardiovascular events
Among 2,749 participants randomized across 16 countries including the U.S., Germany, India, Brazil and South Korea, Foundayo showed a 16% lower risk of MACE-4 (cardiovascular death, heart attack, stroke or hospitalization for unstable angina) versus insulin glargine, with a hazard ratio of 0.84 (95.0% CI: 0.59 to 1.20), meeting the prespecified non-inferiority threshold. The risk of MACE-3 (cardiovascular death, heart attack or stroke) was 23% lower (hazard ratio: 0.77; 95.0% CI: 0.52 to 1.13).
Pre-planned analyses show sharper mortality reductions
In secondary, pre-planned analyses, cardiovascular death risk fell 53% (hazard ratio: 0.47; 95.0% CI: 0.25 to 0.90) and all-cause death risk fell 57% (hazard ratio: 0.43; 95.0% CI: 0.25 to 0.75) for patients on Foundayo compared with insulin glargine. These endpoints were not controlled for family-wise type 1 error.
Cardiometabolic markers improve alongside kidney function
At week 52, Foundayo-treated participants recorded a 7.0 cm reduction in waist circumference, a 4.4 mmHg drop in systolic blood pressure, an 18.9% decline in triglycerides, a 6.6% reduction in non-HDL cholesterol and a 38.9% drop in hsCRP, an inflammation marker. Kidney function decline slowed, with a 2.8 mL/min/1.73 m2 smaller eGFR reduction and 27.1% greater reduction in albuminuria versus insulin glargine.
Discontinuation rate reaches 10.6% during 52-week period
The most common adverse events were nausea, vomiting, diarrhea, decreased appetite and constipation. During the 52-week minimum treatment period, 10.6% of participants on Foundayo discontinued treatment due to adverse events, with the overall safety profile consistent with prior trials and other incretin therapies.
Lilly advances further cardiovascular outcomes research
Thomas Seck, senior vice president of product development at Lilly Cardiometabolic Health, said more than half of ACHIEVE-4 participants reached an A1C of 6.5% or lower on Foundayo. The company is now running ATTAIN-OUTCOMES, a Phase 3 study examining cardiovascular outcomes in adults with obesity or overweight who have established cardiovascular or kidney disease, with or without type 2 diabetes. Orforglipron, discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018, is also under investigation for obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease and stress urinary incontinence. Results were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan and published simultaneously in The Lancet.