GLP-1 Receptor Agonists Linked to Lower Risk of Peptic Ulcer Disease in Patients with T2DM
A nationwide retrospective study of patients with type 2 diabetes mellitus (T2DM) has found a significant association between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and reduced risk of peptic ulcer disease (PUD). The findings suggest that, beyond glycemic and cardiovascular benefits, GLP-1 RAs may offer additional protection against gastrointestinal complications.
Using the NIH “All of Us” database, researchers analyzed data from 66,102 adults with T2DM. After adjusting for insulin use, NSAIDs, steroids, PPIs, and other confounders, GLP-1 RA use was associated with 44% lower odds of PUD diagnosis (adjusted OR 0.56; 95% CI 0.45–0.71; p < 0.001).
A focused subgroup analysis of 3313 patients who were newly started on either GLP-1 RAs or insulin as second-line therapy further supported the protective effect. Patients who initiated GLP-1 RA therapy had a 56% lower hazard of PUD compared to insulin users (adjusted HR 0.44; 95% CI 0.30–0.63; p < 0.001).
The study also confirmed known risk factors: active use of NSAIDs (HR 2.39) and steroids (HR 1.84) were both significantly associated with increased likelihood of PUD.
“These findings indicate an association between GLP-1 RA use and reduced risk of PUD,” the authors concluded. “Switching to GLP-1 RA as second-line therapy was associated with a significantly lower hazard of PUD compared to switching to insulin.”
For gastroenterologists, this evidence may inform collaborative care with endocrinologists when managing patients with T2DM and at risk for GI complications, especially in those with PUD risk factors. The results highlight a potentially favorable GI safety profile of GLP-1 RAs, warranting further investigation into their role in mucosal protection.
Reference
Seika P, Chang J, Hong SM, et al. Glucagon-like peptide-1 receptor agonists are associated with a lower risk of peptic ulcer disease: a nationwide cohort study. Clin Gastroenterol Hepatol. Published online August 25, 2025. doi:10.1016/j.cgh.2025.08.015
