Lilly’s Oral GLP-1, Orforglipron, Succeeds in Third Phase 3 Trial, Paving Way for Global Obesity Filings

Eli Lilly and Company announced that its investigational oral GLP-1 receptor agonist, orforglipron, delivered significant weight loss and blood sugar control in a Phase 3 clinical trial involving adults with obesity or overweight and type 2 diabetes. The results mark the third positive Phase 3 trial for orforglipron, setting the stage for global regulatory submissions later this year.

The ATTAIN-2 trial evaluated three doses of orforglipron taken once daily without food or water restrictions. At 72 weeks, all doses met both the primary and key secondary endpoints. The highest dose led to an average weight loss of 10.5% (22.9 lbs), compared to just 2.2% (5.1 lbs) with placebo.

In addition to weight loss, the drug demonstrated meaningful reductions in A1C levels—a key measure of blood sugar control—with drops between 1.3% and 1.8% from a baseline of 8.1%. Notably, 75% of participants on the highest dose reached an A1C of 6.5% or lower, aligning with the American Diabetes Association’s definition of diabetes control.

Orforglipron also showed benefits across several cardiometabolic risk factors, including improvements in non-HDL cholesterol, systolic blood pressure, and triglycerides. A pre-specified exploratory analysis found that the highest dose reduced high-sensitivity C-reactive protein (hsCRP)—a marker of inflammation—by more than 50%.

Dr. Louis J. Aronne, a leading expert in obesity medicine, praised the results: “These data show the potential for orforglipron to offer an efficacy, safety, and tolerability profile consistent with the injectable GLP-1 class. It could expand options for patients who prefer oral therapies without compromising clinical results.”

With the completion of ATTAIN-2, Lilly has gathered the necessary data to begin global regulatory submissions for orforglipron as a treatment for obesity and type 2 diabetes.