Eli Lilly says oral GLP-1 orforglipron met primary endpoint in Phase 3 trial

Eli Lilly (LLY) announced detailed results from the Phase 3 ATTAIN-1 trial, evaluating the safety and efficacy of orforglipron, an investigational oral glucagon-like peptide-1 receptor agonist, in adults with obesity, or overweight with a weight-related medical problem and without diabetes. At 72 weeks, all three doses of orforglipron met the primary endpoint of superior body weight reduction compared to placebo. In addition, all three doses delivered clinically meaningful results compared to placebo across the key secondary endpoints of body weight reduction, and waist circumference reduction. Results from the trial were presented at the European Association for the Study of Diabetes Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine. “Obesity is a complex, global health challenge – and patients need treatment options that are both effective and easy to integrate into everyday life,” said Sean Wharton, M.D., director at Wharton Medical Clinic and lead investigator. “In this Phase 3 study, orforglipron demonstrated strong efficacy results and safety consistent with the GLP-1 class, reinforcing its potential as a first-line treatment in primary care. Additionally, orforglipron could help reduce known markers of cardiovascular risk associated with obesity and support meaningful improvements in public health.” In the ATTAIN-1 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo, with participants taking the highest dose losing an average of 27.3 lbs at 72 weeks using the efficacy estimand. In key secondary endpoints, 59.6% of participants taking the highest dose of orforglipron lost at least 10% of their body weight, while 39.6% lost at least 15% of their body weight. Among the 1,127 participants who had prediabetes at the start of the study, up to 91% of those taking orforglipron achieved near-normal blood sugar levels compared to 42% of those taking placebo at 72 weeks. Additionally, orforglipron showed clinically meaningful improvements across key cardiovascular risk factors often associated with obesity, including non-HDL cholesterol, systolic blood pressure and triglycerides. In a pre-specified exploratory analysis, the highest dose of orforglipron reduced high-sensitivity C-reactive protein levels, a marker of inflammation, by 47.7%.