Orforglipron - (ACHIEVE-4)

April 16, 2026: Eli Lilly and Company (NYSE: LLY) reported positive topline results from the Phase 3 ACHIEVE-4 trial (NCT05803421) of Foundayo (orforglipron), an oral GLP-1 receptor agonist, versus insulin glargine in adults with type 2 diabetes and overweight/obesity at increased cardiovascular risk (n=2,749; 15 countries). The primary endpoint was met: Foundayo was non-inferior to insulin glargine for time to first MACE-4 (CV death, MI, stroke, or hospitalization for unstable/sudden chest pain), HR 0.84 (95% CI 0.59–1.20; p=0.336), meeting the non-inferiority criterion (upper CI <1.8). Key secondary MACE-3 favored Foundayo but was not statistically significant: HR 0.77 (95% CI 0.52–1.13; p=0.181). At 52 weeks, Foundayo showed superior A1C reduction (-1.6% vs -1.0%; ETD -0.66; p<0.001) and weight loss (-8.8% vs +1.7%; ETD -10.42%; p<0.001), with effects reported to persist through 104 weeks. A pre-planned analysis (not multiplicity-controlled) showed lower all-cause death risk: HR 0.43 (95% CI 0.25–0.75; p=0.002). Lilly said it plans to submit Foundayo to the FDA for type 2 diabetes by end of Q2, using the Commissioner’s National Priority Review Voucher.