Atrial fibrillation reporting with semaglutide versus tirzepatide in eudravigilance: a comparative disproportionality analysis

Background/Introduction Incretin-based therapies, particularly GLP-1 receptor agonists and dual GIP/GLP-1 agonists, are widely used for metabolic disease and, more recently, obesity, with several trials suggesting neutral or even protective effects on atrial fibrillation. As use expands and rare events begin to surface in pharmacovigilance systems, it becomes important to characterise and compare atrial fibrillation reporting patterns between individual agents in real-world practice. Purpose To compare atrial fibrillation reporting associated with semaglutide and tirzepatide within the EudraVigilance database, using metformin as a reference comparator. Methods Individual case safety reports submitted to EudraVigilance up to 9 November 2025 were retrieved. For semaglutide, tirzepatide and metformin, total reports and atrial fibrillation specific reports were extracted. Atrial fibrillation reporting proportions were calculated as atrial fibrillation reports divided by total reports for each medicine. Data were summarised descriptively and prepared for visualisation through two figures: atrial fibrillation reporting proportion and absolute total versus atrial fibrillation case counts. Results Semaglutide generated 45,364 total reports, including 240 atrial fibrillation cases (0.53 per cent). Tirzepatide generated 22,606 total reports, including 115 atrial fibrillation cases (0.51 per cent). Metformin generated 48,405 total reports, including 3,436 atrial fibrillation cases (7.10 per cent). Absolute atrial fibrillation case volume was substantially higher for metformin compared with the incretin-based therapies. Conclusion(s) In this large pharmacovigilance analysis, atrial fibrillation reporting for semaglutide and tirzepatide was low and comparable, and markedly lower than metformin. These data align with the emerging evidence suggesting a generally reassuring atrial fibrillation profile for incretin-based therapies, while demonstrating how comparative real-world surveillance can meaningfully inform ongoing debates about arrhythmia-related safety signals as these agents continue to expand in use.