Effect of Tirzepatide on arrhythmic, major cardiovascular, and neurological outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective for glycemic control in type 2 diabetes (T2D), but its impact on cardiovascular (CV) and neurological safety remains uncertain. This meta-analysis evaluated the risks of arrhythmic, major CV, and neurological outcomes associated with tirzepatide. METHODS: A comprehensive search of the PubMed, Embase, and Cochrane databases was conducted to identify eligible randomized controlled trials (RCTs) reporting arrhythmic, major CV, and neurological outcomes published up to February 2025. Additionally, subgroup analyses were conducted by age, BMI, diabetes duration, and comparator type. RESULTS: Twelve RCTs involving 10,615 patients with T2D were included. Tirzepatide was not associated with a statistically significant increase in arrhythmic outcomes, including atrial fibrillation (AF) (RR 1.39, 95% CI 0.53 to 3.67) and atrial flutter (AFL) (RR 1.14, 95% CI 0.20 to 6.55). For major CV outcomes, no significant differences were observed for acute myocardial infarction (RR 0.66, 95% CI 0.38 to 1.17) or coronary artery disease (RR 0.62, 95% CI 0.32 to 1.18). Neurologically, tirzepatide significantly increased the risk of dizziness (RR 1.64, 95% CI 1.04 to 2.57), whereas the risks of headache (RR 1.00, 95% CI 0.65 to 1.55) and transient ischemic attack (RR 1.43, 95% CI 0.44 to 4.61) were not significant. Subgroup analyses suggested higher dizziness risk in patients aged ≤ 60 years. CONCLUSIONS: Tirzepatide does not significantly increase arrhythmic or major CV risks but is associated with a higher risk of dizziness. Findings from CV and neurological perspectives support targeted patient monitoring and guide future prospective studies.