The US Food and Drug Administration has approved orforglipron (Foundayo), a once-daily oral glucagon-like peptide-1 (GLP-1) receptor agonist from Eli Lilly and Company, for chronic weight management to reduce excess body weight and maintain weight reduction in adults with obesity or overweight with weight-related medical conditions.
When used with a reduced-calorie diet and increased physical activity, orforglipron demonstrated significant weight loss in the phase 3 ATTAIN clinical trial program. In the ATTAIN-1 trial, patients receiving the highest dose who remained on treatment lost a mean of 27.3 pounds (12.4%) compared with 2.2 pounds (0.9%) among those receiving placebo. Across all participants regardless of treatment adherence, mean weight loss was 25 pounds (11.1%) vs 5.3 pounds (2.1%) with placebo.
Treatment with orforglipron was also associated with reductions in multiple cardiometabolic risk markers, including waist circumference, non–high-density lipoprotein cholesterol, triglycerides, and systolic blood pressure.
Orforglipron is a nonpeptide, small-molecule oral agent that can be administered once daily without restrictions related to food or water intake.
The ATTAIN phase 3 clinical development program includes two global randomized, double-blind, placebo-controlled trials enrolling more than 4,500 participants. ATTAIN-1 evaluated adults with obesity or overweight with weight-related comorbidities and without diabetes, while ATTAIN-2 enrolled adults with obesity or overweight and type 2 diabetes. The primary endpoint in both trials was body weight reduction at 72 weeks.
Safety considerations include a warning that orforglipron may cause tumors in the thyroid, including thyroid cancer, and it should not be used in patients with a personal or family history of medullary thyroid carcinoma or in those with multiple endocrine neoplasia syndrome type 2. Common adverse events included nausea, diarrhea, constipation, and vomiting.
The drug will be available via LillyDirect, with prescriptions accepted immediately and shipping beginning April 6, followed by broader availability through retail pharmacies and telehealth providers.
According to the manufacturer, eligible commercially insured patients may pay as little as $25 per month with a savings program, while self-pay pricing starts at $149 per month. Eligible Medicare Part D patients may be able to access the drug for about $50 per month beginning as soon as July 1, 2026.
Source: Eli Lilly and Company
