Eli Lilly and Company shared detailed results from a phase 3 trial evaluating the safety and efficacy of orforglipron, an oral glucagon-like peptide-1 (GLP-1) receptor agonist, compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone.
At 40 weeks, all three doses (3 mg, 12 mg, 36 mg) of orforglipron in the ACHIEVE-1 trial achieved the primary endpoint of superior A1C reduction. In addition, the 12 mg and 36 mg doses showed clinically meaningful and statistically significant reductions in body weight vs. placebo. While participants in ACHIEVE-1 did not appear to reach a weight plateau, longer-duration trials, such as the ATTAIN trials, will provide a comprehensive evaluation of the safety and efficacy of orforglipron for the treatment of obesity.
In ACHIEVE-1, orforglipron had a safety profile similar to the established GLP-1 class, and the most frequently reported adverse events were gastrointestinal-related.
The results were presented at the American Diabetes Association 85th Scientific Sessions 2025 and simultaneously published in The New England Journal of Medicine.
According to Lilly, orforglipron is the first oral small molecule (non-peptide) GLP-1 receptor agonist, taken without food and water restrictions, to successfully complete a phase 3 trial.