1722-P: Effect of Tirzepatide on Cardiac Arrhythmia in Adults with Type 2 Diabetes and Obesity: A Systematic Review and Meta-Analysis

Introduction and Objective: This systematic review and meta-analysis aimed to evaluate the risk of cardiac arrhythmias associated with tirzepatide in patients with type 2 diabetes mellitus (T2DM) and obesity. Methods: We systematically searched PubMed, Web of Science, Scopus, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for randomized controlled trials (RCTs) from inception through October 11, 2025. The primary outcome was the incidence of composite cardiac arrhythmias. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed-effects model (I² < 50%), with robustness validated via sensitivity analyses. This review was prospectively registered in PROSPERO (CRD420251237091). Results: A total of 16 RCTs (n = 12,809), encompassing the SURPASS and SURMOUNT programs, were identified for analysis. Compared with placebo or other active comparators, tirzepatide did not increase the overall risk of cardiac arrhythmias (RR 1.40, 95% CI 0.98-2.00, I² = 0.0%) or atrial fibrillation (RR 1.53, 95% CI 0.91-2.58, I² = 0.0%). However, significantly elevated risks treated with tirzepatide were identified in specific clinical subgroups: patients with impaired renal function (eGFR < 90 mL/min/1.73 m²: RR 1.60, 95% CI 1.02-2.52, I² = 0.0%) and those with obesity (BMI > 30 kg/m²: RR 1.48, 95% CI 1.02-2.15, I² = 0.0%). Furthermore, long-term exposure (> 52 weeks) was associated with an increased risk of arrhythmic events (RR 1.49, 95% CI 1.02-2.16, I²=0.0%). Conclusion: Tirzepatide demonstrates a favorable overall cardiac safety profile regarding arrhythmias. Nevertheless, caution is warranted in patients with renal impairment or a high BMI. Given the potential risk increase with extended use, regular clinical electrocardiographic monitoring and risk assessments are recommended for patients on long-term therapy (> 52 weeks). Disclosure S. Chen: None. X. Zhou: None. M. Guo: None. Y. Xu: None. Funding This study was supported by the Natural Science Foundation of China (Nos. U22A20286, 82300911, and 82470854), the Sichuan Science and Technology Program (2025ZNSFSC1622), and the Scientific Research Projects of Southwest Medical University (2025LCYXZX42).