Ann Intern Med

GLP-1 agonists and tirzepatide show comparable GI safety in real-world study

November 14, 2025

A large U.S. cohort study compared dulaglutide, semaglutide, and tirzepatide in adults with type 2 diabetes and found similar rates of severe GI adverse events—including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation. Across >130,000 matched pairs, hazard ratios ranged from 0.96 to 1.07, indicating no clinically meaningful differences among the three drugs. These findings provide reassurance that GI safety profiles are comparable, allowing clinicians to prioritize glycemic efficacy, weight effects, and patient preferences when selecting therapy.

Clinical takeaway: Monitor for GI symptoms as usual, but drug choice can focus on efficacy and patient goals rather than differential GI risk.

Source:

Crisafulli S, et al. (2025, November 4). Ann Intern Med. Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes. https://pubmed.ncbi.nlm.nih.gov/41183330/