Eli Lilly announces ATTAIN-2 trial met primary, secondary endpoints

Eli Lilly (LLY) announced topline results from the Phase 3 ATTAIN-2 trial, evaluating orforglipron, an investigational oral GLP-1 receptor agonist, in adults with obesity or overweight and type 2 diabetes. In the trial, all three doses of orforglipron met the primary and all key secondary endpoints, delivering significant weight loss, meaningful A1C reductions, and improvements in cardiometabolic risk factors at 72 weeks. For the primary endpoint, orforglipron 36 mg, taken once per day without food and water restrictions, lowered weight by an average of 10.5% compared to 2.2% with placebo using the efficacy estimand. With the completion of ATTAIN-2, Lilly now has the full clinical data package required to initiate global regulatory submissions for orforglipron. In the ATTAIN-2 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo. Participants taking the highest dose of orforglipron lost an average of 22.9 lbs at 72 weeks using the efficacy estimand. In a key secondary endpoint, orforglipron lowered A1C by 1.3% to 1.8% from a baseline of 8.1% across doses. In another key secondary endpoint, 75% of participants taking the highest dose of orforglipron achieved an A1C of 6.5%, which is at or below the American Diabetes Association’s definition of diabetes. Additionally, orforglipron showed clinically meaningful benefits across key cardiovascular risk factors, 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 50.6%. For the treatment-regimen estimand, each dose of orforglipron led to statistically significant improvements across the primary and all key secondary endpoints. The overall safety profile of orforglipron in ATTAIN-2 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 were nausea vs. 8.4% with placebo, vomiting vs. 3.8% with placebo, diarrhea vs. 15% with placebo, constipation vs. 7.8% with placebo, and dyspepsia vs. 3.5% with placebo. Treatment discontinuation rates due to adverse events were 6.1%, 10.6% and 10.6% for orforglipron vs. 4.6% with placebo. Overall treatment discontinuation rates were balanced across the treatment groups with 19.1%, 22.3% and 20.5% for orforglipron vs. 20% with placebo. No hepatic safety signal was observed. Detailed ATTAIN-2 results will be presented at a future medical meeting and published in a peer-reviewed journal.