Eli Lilly and Company reported positive topline results from the Phase 3 ACHIEVE-4 trial evaluating Foundayo (orforglipron) versus insulin glargine in adults with type 2 diabetes and overweight or obesity at increased cardiovascular risk. ACHIEVE-4 is the largest and longest Phase 3 study of Foundayo in type 2 diabetes to date, enrolling more than 2,700 participants across 15 countries. The trial met its primary endpoint by demonstrating non-inferiority of Foundayo to insulin glargine for time to first major adverse cardiovascular event (MACE-4: cardiovascular death, heart attack, stroke, or hospitalization for unstable or sudden chest pain).
In ACHIEVE-4, the risk of MACE-4 events was 16% lower with Foundayo compared with insulin glargine (hazard ratio 0.84; 95.0% CI: 0.59 to 1.20), meeting prespecified non-inferiority criteria requiring the upper bound of the 95.0% confidence interval to be below 1.8. Foundayo also produced superior reductions in A1C and body weight at 52 weeks versus insulin glargine, with these effects maintained through 104 weeks of treatment. In a pre-specified analysis not adjusted for multiplicity, the risk of all-cause death was 57% lower for Foundayo compared with insulin glargine (hazard ratio 0.43; 95.0% CI: 0.25 to 0.75; nominal p=0.002).
Lilly reported that Foundayo led to clinically meaningful improvements from baseline in several cardiovascular risk factors, including non–HDL cholesterol, systolic blood pressure, triglycerides, and high-sensitivity C-reactive protein (hsCRP). The overall safety and tolerability profile of Foundayo in ACHIEVE-4 was generally consistent with previous trials and the GLP‑1 receptor agonist class, with the most common adverse events including nausea, vomiting, diarrhea, decreased appetite, and constipation; 10.6% of participants discontinued Foundayo during the 52‑week minimum treatment period due to adverse events. The trial incorporated a detailed assessment of potential drug-induced liver injury, and Lilly reported no hepatic safety signal, in line with prior ACHIEVE and ATTAIN studies.
Lilly plans to submit a regulatory application for Foundayo for the treatment of type 2 diabetes to the U.S. Food and Drug Administration by the end of the second quarter of 2026 under the Commissioner’s National Priority Review Voucher program. ACHIEVE-4 is part of a broader Phase 3 program in which seven studies have enrolled more than 11,000 patients with type 2 diabetes.
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