Eli Lilly and Company (NYSE:LLY), the maker of Zepbound (tirzepatide), today announced detailed results from the Phase 3 ACHIEVE-4 trial evaluating the efficacy and safety of Foundayo (orforglipron) compared to titrated insulin glargine in adults with type 2 diabetes and obesity or overweight at increased cardiovascular risk. In the trial, which is the largest and longest study of this medicine in type 2 diabetes to date, Foundayo demonstrated a non-inferior risk of major adverse cardiovascular events (MACE) and improved A1C, weight and other key measures of cardiometabolic health compared with insulin glargine. Results from the trial were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, and simultaneously published in The Lancet.

"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. "ACHIEVE-4 reaffirmed the safety of orforglipron and demonstrated an association with a lower risk of major cardiovascular events and death. These results, paired with the simple administration of a once-daily pill, taken without fasting or water restrictions, could make orforglipron a compelling potential option across the globe."

In the trial, the risk of cardiovascular death, heart attack, stroke, or hospitalization for unstable sudden chest pain (MACE-4) was 16% lower for Foundayo vs. insulin glargine (hazard ratio: 0.84; 95.0% CI: 0.59 to 1.20), meeting the prespecified criteria for demonstrating non-inferiority (upper limit of 95.0% CI of the hazard ratio < 1.8).1 The risk of cardiovascular death, heart attack, or stroke (MACE-3) was 23% lower for Foundayo vs. insulin glargine (hazard ratio: 0.77; 95.0% CI: 0.52 to 1.13). In pre-planned analyses, the risk of cardiovascular death was 53% lower (hazard ratio: 0.47; 95.0% CI: 0.25 to 0.90) and the risk of all-cause death was 57% lower (hazard ratio: 0.43; 95.0% CI: 0.25 to 0.75) for Foundayo vs. insulin glargine.2

In addition to demonstrating cardiovascular safety, Foundayo was associated with meaningful improvements across multiple cardiovascular risk factors. At week 52, participants treated with Foundayo experienced reductions in waist circumference by 7.0 cm, systolic blood pressure by 4.4 mmHg, triglycerides by 18.9%, non-HDL cholesterol by 6.6% and hsCRP, a marker of inflammation, by 38.9%.2 Foundayo was also associated with a slower decline in kidney function, a key contributor to cardiovascular risk, including a 2.8 mL/min/1.73 m² smaller reduction in eGFR and a 27.1% greater reduction in albuminuria compared to insulin glargine.2