N Engl J Med
EASD 2025: Orforglipron yields meaningful weight loss in adults with obesity
Orforglipron, a small-molecule, oral GLP-1 receptor agonist, offers a promising oral alternative to injectable GLP-1 therapies with a robust efficacy and a tolerable safety profile, according to findings presented at the 2025 European Association for the Study of Diabetes (EASD) annual meeting. Its convenience and scalability could expand access to obesity treatment, particularly for patients unable or unwilling to use injectables.
Study details: The Phase 3 ATTAIN-1 trial (NCT05869903) evaluated orforglipron in 3,127 adults with obesity but without diabetes. Participants were randomized to receive 6 mg, 12 mg, or 36 mg orforglipron, or placebo, once daily for 72 weeks. Primary endpoint was percent change in body weight from baseline.
Results: Orforglipron was associated with dose-dependent weight loss: −7.5% (6 mg), −8.4% (12 mg), and −12.4% (36 mg) vs. −0.9% with placebo (p<.001 for all). At the highest dose, 59.6% of participants lost ≥10% of body weight, and 39.6% lost ≥15%. Cardiometabolic markers (including systolic blood pressure, triglycerides, and non-HDL cholesterol) also improved. Adverse events were mostly mild to moderate GI symptoms; discontinuation rates ranged from 5.3% to 10.3%.
Sources:
Wharton S, et al; ATTAIN-1 Trial Investigators. (2025, September 16). N Engl J Med. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. https://pubmed.ncbi.nlm.nih.gov/40960239/
(2025, September 16). Eli Lilly and Company. Lilly's oral GLP-1, orforglipron, demonstrated meaningful weight loss and cardiometabolic improvements in complete ATTAIN-1 results published in The New England Journal of Medicine. [News release]. https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-meaningful-weight