Clinical effectiveness of tirzepatide for patients with atrial fibrillation and type 2 diabetes: A retrospective cohort study.

AIM: This study aimed to evaluate whether tirzepatide is associated with a reduced atrial fibrillation (AF) burden in patients with type 2 diabetes (T2D). METHODS: A retrospective cohort study was conducted using the TriNetX database. Adults with both AF and T2D diagnosed between January 2022 and February 2025 were included. The primary outcome was a composite of cardioversion, intravenous antiarrhythmic drug use, and AF ablation. Secondary outcomes included each component of the composite, heart failure, ischemic stroke, and all-cause mortality. Propensity score matching and Cox models were used. Subgroup analyses were conducted based on AF type, coronary artery disease, chronic kidney disease, heart failure, and obesity. RESULTS: After matching, 11,194 patients were analyzed. Tirzepatide use was associated with a significantly lower risk of the primary outcome (HR: 0.65; 95 % CI: 0.55-0.76; P < 0.001). Significant findings were also observed across all secondary outcomes, including cardioversion, intravenous antiarrhythmic therapy, atrial fibrillation ablation, heart failure, ischemic stroke, and all-cause mortality. These associations remained consistent across prespecified subgroups and multiple sensitivity analyses. CONCLUSION: Tirzepatide was significantly associated with reduced AF burden in patients with T2D and AF. These findings suggest a potential therapeutic role, supporting further prospective evaluation. Condensed abstract Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown metabolic and cardiovascular benefits, but its impact on AF burden remains unclear. Using the TriNetX database, this study analyzed 11,194 patients with AF and T2D and found that tirzepatide use was significantly associated with a lower two-year risk of cardioversion, intravenous antiarrhythmic drug use, and AF ablation (HR: 0.65; 95 % CI: 0.55-0.76; P < 0.001). These findings suggest that tirzepatide may offer therapeutic benefits in this high-risk population, warranting further investigation through randomized clinical trials.