Comparison of cardiac adverse event signal profiles for GLP-1 receptor agonists: an analysis of the FAERS database

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes owing to their effectiveness in glycemic control and weight reduction. Given the increasing use of GLP-1RAs, further research is warranted to better understand their cardiac effects. Individual Case Safety Reports from the U. S. Food and Drug Administration Adverse Event Reporting System database from July 6, 2007, to February 17, 2026, were evaluated for the post-marketing cardiac adverse events associated with dulaglutide, liraglutide, semaglutide, and tirzepatide. 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 variables and to estimate odds ratios. A total of 7,023 cardiac adverse events were identified among 305,877 reports. GLP-1RAs were associated with a higher reporting frequency of tachyarrhythmias than bradyarrhythmias. In the 65–85-year age group, an increase in the signal for cardiac events was observed. Pairwise post hoc comparisons demonstrated no statistically significant differences in reporting frequency of cardiac events between semaglutide and liraglutide, whereas all other drug pairs demonstrated statistically significant differences. Semaglutide and liraglutide had higher relative reporting of cardiac events whereas tirzepatide had lower PRR and ROR values against the total background of reports. These findings suggest a lower reporting tendency of cardiac events for tirzepatide. This study may assist healthcare professionals in recognizing the frequency of cardiac events associated with GLP-1RA use and drive new hypotheses to clarify underlying mechanisms.