Cardiovascular adverse event reporting profile of tirzepatide: a real-world pharmacovigilance analysis of heart failure, arrhythmias, and ischemic events.

BACKGROUND: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, is highly effective for glycaemic control and weight reduction. However, its real-world cardiovascular adverse event reporting profile remains incompletely characterised. METHODS: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) from the second quarter of 2022 (FDA approval of tirzepatide) through the third quarter of 2025. Disproportionality analysis was performed using the Reporting Odds Ratio (ROR) with a concurrent full-database comparator (all other drugs reported in the same quarterly files). Because consumers submitted 92.3% of reports, primary inference was drawn from analyses restricted to healthcare professional (HCP) reports (physicians and pharmacists). Subgroup analyses stratified by age, sex, and body weight were conducted; weight-stratified analyses were confined to reports with documented body weight. RESULTS: A total of 103,693 unique tirzepatide reports were identified. Consumers accounted for 92.3% of submissions; body weight was documented in 5,881 reports (5.7%). In HCP-restricted analyses, tirzepatide was associated with persistently lower reporting odds for heart failure (ROR 0.18 [95% CI 0.07-0.43]). Similarly, no disproportionate reporting was detected for acute myocardial infarction (ROR 0.45 [0.19-1.08]), while remarkably, zero cases of angina or myocardial ischemia were reported in the HCP cohort. In contrast, no association was detected for atrial fibrillation (ROR 1.02 [0.58-1.80]) or tachycardia (ROR 1.01 [0.68-1.51]) in HCP reports. In weight-stratified analyses (full dataset, restricted to reports with documented weight), elevated RORs for tachycardia were observed in both weight groups (<95 kg: 1.91 [1.54-2.37]; ≥95 kg: 1.57 [1.20-2.05]); however, this finding was not replicated in the HCP-restricted analysis and should be interpreted with caution. CONCLUSION: In this real-world FAERS analysis using a concurrent full-database comparator and pre-specified stratification by reporter type, tirzepatide showed disproportionately low reporting of heart failure that was robust in HCP reports and across all subgroups. No reporting signal for atrial fibrillation, tachycardia, or ischemic events was detected after accounting for reporter bias. These findings provide pharmacovigilance evidence that complements the safety database of tirzepatide and generate hypotheses for ongoing cardiovascular outcome trials.