Comparison of Cardiac Adverse Event Signal Profiles for GLP-1 Receptor Agonists: An Analysis of the FAERS Database

Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained popularity in the management of type 2 diabetes mellitus owing to their effectiveness in glycemic control and weight reduction. Despite the increasing use of GLP-1RAs, data on their cardiac safety remain conflicting. In this study, we aimed to analyze and compare the post-marketing signals of cardiac adverse events associated with four different GLP-1RAs (dulaglutide, liraglutide, semaglutide, and tirzepatide) using the United States Food and Drug Administration Adverse Event Reporting System database. Methods Individual Case Safety Reports from July 6, 2007, to February 17, 2026, were retrospectively analyzed. To detect signal differences among drugs, disproportionality analysis was conducted using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) methods, along with standard statistical tests to evaluate categorical distributions and odds ratios. Results A total of 7,023 cardiac adverse events were identified. Pairwise post hoc comparisons demonstrated no statistically significant differences in cardiac adverse event reporting between semaglutide and liraglutide, whereas all other drug pairs showed statistically significant differences. Disproportionality analysis yielded positive signals for semaglutide and liraglutide, whereas dulaglutide and tirzepatide showed lower signal values. Conclusion GLP-1RAs appear more prone to causing tachyarrhythmias than bradyarrhythmias. Cardiac adverse events were reported more frequently with semaglutide; however, fatal outcomes from these events were reported less frequently. Tirzepatide showed lower PRR and ROR values for cardiac adverse events. These results support the favorable cardiac safety signal for tirzepatide, which may be attributed to its unique mechanism of action.