Esophagus to Small Intestine
Gut. 2024;73(2):246–54
Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastroesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: A population-level retrospective matched cohort study
Background: Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastroesophageal reflux disease (GERD) and its complications.
Aim: To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications
Design: The authors used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated 2 cohorts totaling 1,543,351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), they analyzed outcomes and separately examined outcomes in patients starting short-acting (≤ 1 day) and long-acting (≥ 5 days) GLP-1 RAs.
Results: 177,666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR = 1.15; 95% confidence interval [CI]: 1.09–1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR = 1.215; 95% CI: 1.111–1.328), but not long-acting (HR = 0.994; 95% CI: 0.924–1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of esophageal stricture (HR = 1.284; 95% CI: 1.135–1.453), Barrett's without dysplasia (HR = 1.372; 95% CI: 1.217–1.546) and Barrett's with dysplasia (HR = 1.505; 95% CI: 1.164–1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide.
Conclusion: Starting shorter-acting glucagon-like peptide-1 receptor agonists is associated with increased risks of gastroesophageal reflux disease and its complications.