Eli Lilly announced positive topline results from its Phase 3 ATTAIN-2 trial of orforglipron, the company’s first-in-class oral GLP-1 receptor agonist for obesity and type 2 diabetes.
The 72-week, double-blind trial enrolled more than 1,600 adults with obesity or overweight and type 2 diabetes across 11 countries. Orforglipron, taken once daily without food or water restrictions, met its primary endpoint of superior body weight reduction versus placebo, along with all key secondary endpoints.
- At the highest 36 mg dose, patients lost 10.5% of body weight (22.9 lbs) compared to 2.2% (5.1 lbs) with placebo.
- A1C dropped by 1.8% from baseline, with 75% of participants reaching an A1C ≤6.5%.
- Clinically meaningful improvements were also observed in non-HDL cholesterol, triglycerides, blood pressure, and inflammation (hsCRP reduced by 50.6%).
The safety profile mirrored that of the GLP-1 class, with gastrointestinal events (nausea, vomiting, diarrhea, constipation) being the most common. Discontinuation rates were modest (6–11% across doses vs. 4.6% placebo). No hepatic safety concerns were observed.
With ATTAIN-2 completed, Lilly now has the full data package needed to initiate global regulatory submissions later this year. “If approved, orforglipron could redefine obesity treatment by offering a scalable, once-daily oral option,” said Kenneth Custer, PhD, Lilly’s president of Cardiometabolic Health.
Detailed trial results will be presented at a future medical meeting and submitted for peer-reviewed publication. Lilly is also evaluating orforglipron in other obesity-related conditions, including obstructive sleep apnea and hypertension.
