Glucagon-like peptide-1 receptor agonists and impaired gastric emptying: a pharmacovigilance analysis of the US Food and Drug Administration adverse event reporting system

Abstract

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) potentially increase the risk of pulmonary aspiration resulting from impaired gastric emptying (IGE). We evaluated the association between GLP-1RAs and IGE using the US Food and Drug Administration Adverse Event Reporting System (FAERS). MethodsWe analysed FAERS data from 2004 Q1 to 2024 Q1, identifying the top 10 drugs linked to IGE and determining the proportion of GLP-1RA use. Disproportionality analysis using the reporting odds ratio was conducted to assess the relative IGE risk for each drug. Logistic regression analysed the impact of age, weight, and sex on IGE risk. Cumulative incidence and time to onset of IGE events were examined using Kaplan–Meier and Weibull shape parameter tests. ResultsAmong the top 10 drugs associated with IGE reports, five were GLP-1RAs, accounting for 49.5% (982/1982) of cases. Dulaglutide (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.94–1.00, P=0.033) and semaglutide (OR 0.96, 95% CI 0.94–0.97, P=0.001) showed lower IGE risk with older age. For exenatide, higher weight (OR 0.99, 95% CI 0.98–1.00, P=0.033) and male sex (OR 0.39, 95% CI 0.20–0.68, P=0.033) were associated with lower IGE risk. Median onset times ranged from 40.5 days (semaglutide) to 107.5 days (tirzepatide) from intitiation of therapy. The Weibull shape parameter β was <1 for all GLP-1RAs, indicating a higher IGE risk early in treatment. ConclusionsGLP-1RAs were notably associated with reports of impaired gastric emptying in the FAERS. Age, weight, and sex were significantly associated with impaired gastric emptying risk for certain GLP-1RAs. IGE events tended to occur early in treatment, with risk diminishing over time. These findings provide valuable references for future research on perioperative safety with GLP-1RAs.