Glucagon-like Peptide-1 Receptor Agonists Are Associated With a Lower Risk of Peptic Ulcer Disease: A Nationwide Cohort Study

Abstract

Background & aims: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed for type 2 diabetes mellitus (T2DM) to improve glycemic control and lower cardiovascular risk. Although the impact of GLP-1RAs on gastrointestinal motility has been characterized, their association with mucosal damage, such as in peptic ulcer disease (PUD), has received little attention.

Methods: We conducted a nationwide retrospective study of adults with T2DM using the "All of Us" National Institutes of Health database, including a sub-group analysis of adults who were newly initiated on GLP-1RAs or insulin as second-line therapy. Our primary outcome was the odds of PUD diagnosis after time-dependent use of GLP-1RAs, adjusting for use of insulin, nonsteroidal anti-inflammatory drugs, steroids, and proton pump inhibitors and other confounders. In a subgroup analysis, we used a weighted, time-varying Cox proportional hazards model, while accounting for the competing risks of death and gastrectomy.

Results: A total of 66,102 participants with T2DM were identified and included in our primary analysis. After adjusting for possible confounders, GLP-1RAs were associated with significantly lower odds of PUD diagnosis (adjusted odds ratio 0.56; 95% confidence interval, 0.45-0.71; P < .001). Our subgroup included a total of 3313 patients (1270 new GLP-1RA users; 2043 new insulin users). In this analysis, switching to a GLP-1RA as second-line therapy was associated with a significantly lower hazard of PUD compared with switching to insulin (adjusted hazard ratio [HR], 0.44; 95% confidence interval, 0.30-0.63; P < .001). The model confirmed that active use of nonsteroidal anti-inflammatory drugs (HR, 2.39) and steroids (HR, 1.84) were also associated with increased likelihood of PUD.

Conclusions: In this nationwide cohort study of patients with T2DM, GLP-1RA use was associated with 44% lower odds of PUD. In our propensity score-matched subgroup, switching to GLP-1RA as second-line therapy was associated with a 56% lower hazard of PUD vs insulin. These findings indicate an association between GLP-1RA use and reduced risk of PUD.

Keywords: Glucagon-; Peptic Ulcer Disease; Type 2 Diabetes Mellitus; ike Peptide-1 Receptor Agonists.