Eli Lilly and Company announced detailed results today from a Phase 3 trial showing its oral glucagon-like peptide-1 (GLP-1) receptor agonist, orforglipron, delivered superior blood sugar control and weight loss compared to oral semaglutide in adults with type 2 diabetes. The findings, published in The Lancet, come from the ACHIEVE-3 trial, which enrolled 1,698 participants inadequately controlled with metformin.
The study demonstrated that orforglipron 36 mg lowered A1C by 2.2% versus 1.4% with oral semaglutide 14 mg. Participants taking the 36 mg dose of orforglipron also experienced a weight loss of 19.7 pounds, or 9.2% of their body weight, compared to 11.0 pounds, or 5.3%, for those on oral semaglutide 14 mg. This represents a 73.6% greater relative weight loss, according to Lilly.
“ACHIEVE-3 gives us the first head-to-head comparison between two oral GLP-1 receptor agonist therapies in adults with type 2 diabetes, and the differences were clinically meaningful,” said Dr. Julio Rosenstock, clinical professor of medicine at the University of Texas Southwestern Medical Center and lead investigator of the trial. “Orforglipron 12 mg and 36 mg doses outperformed oral semaglutide 7 mg and 14 mg diabetes-related doses on every key endpoint we measured, including A1C and weight loss, with improvements appearing as early as four weeks and sustained throughout the study.”
Orforglipron is a small molecule oral GLP-1, designed for administration without food or water restrictions. Lilly has submitted the drug to regulators in over 40 countries and anticipates a potential U.S. Regulatory action for obesity in the second quarter of 2026. The ACHIEVE-3 trial included four treatment arms: orforglipron 12 mg and 36 mg, and oral semaglutide 7 mg and 14 mg. The primary endpoint focused on the change in A1C from a baseline of 8.3% at week 52.
The research builds on preclinical pharmacology data previously published with Chugai. Lilly is also conducting Phase 3 studies evaluating orforglipron for weight management, in addition to its use in treating type 2 diabetes.
