Eli Lilly has announced detailed results from the phase-III ATTAIN-1 trial, evaluating the safety and efficacy of Orforglipron, an investigational oral Glucagon-Like Peptide-1 (GLP-1) receptor agonist, in adults with obesity, or overweight with a weight-related medical problem and without diabetes. At 72 weeks, all three doses (6 mg, 12 mg and 36 mg) 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 (≥10 percent, ≥15 percent and ≥20 percent) and waist circumference reduction. Results from the trial were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine.

Sean Wharton, MD, Director, Wharton Medical Clinic and lead investigator, said, "Obesity is a complex, global health challenge—and patients need treatment options that are both effective and easy to integrate into everyday life. In this phase-III 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 (12.4 percent) at 72 weeks using the efficacy estimand. In key secondary endpoints, 59.6 percent of participants taking the highest dose of Orforglipron lost at least 10 percent of their body weight, while 39.6 percent lost at least 15 percent of their body weight. Among the 1,127 participants who had prediabetes at the start of the study, up to 91 percent of those taking Orforglipron achieved near-normal blood sugar levels compared to 42 percent 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 (hsCRP) levels, a marker of inflammation, by 47.7 percent.

Kenneth Custer, PhD, Executive Vice President and President, Lilly Cardiometabolic Health, said, "People living with obesity have broad and varied needs—whether it's improving weight, A1C, lipids, blood pressure, or other health markers that primary care physicians routinely address with their patients. We're encouraged to see Orforglipron improve many of these areas in ATTAIN-1. As a convenient, once-daily pill that can be scaled globally, Orforglipron could be ideally suited for early adoption in primary care—where proactive intervention has the potential to lead to meaningful, long-term health improvements."

The safety profile of Orforglipron in ATTAIN-1 was consistent with the established GLP-1 receptor agonist class. The most commonly reported adverse events were gastrointestinal-related and generally mild-to-moderate in severity. The most common adverse events for participants treated with Orforglipron (6 mg, 12 mg and 36 mg, respectively) were nausea (28.9 percent, 35.9 percent and 33.7 percent) vs. 10.4 percent with placebo, constipation (21.7 percent, 29.8 percent and 25.4 percent) vs. 9.3 percent with placebo, diarrhoea (21 percent, 22.8 percent and 23.1 percent) vs. 9.6 percent with placebo, and vomiting (13 percent, 21.4 percent and 24 percent) vs. 3.5 percent with placebo. Treatment discontinuation rates due to adverse events were 5.3 percent (6 mg), 7.9 percent (12 mg) and 10.3 percent (36 mg) for Orforglipron vs. 2.7 percent with placebo. No hepatic safety signal was observed.

Lilly is advancing Orforglipron towards global regulatory submissions for the treatment of obesity, with regulatory action expected to occur as early as next year. Submission for the treatment of type-II diabetes is anticipated in 2026.