Association between antidiabetic drugs and the incidence of atrial fibrillation in patients with type 2 diabetes: A nationwide cohort study in South Korea

Background: Although diabetes is a risk factor for atrial fibrillation (AF), studies on the AF risk according to the antidiabetic drugs are lacking. This study evaluated the effects of antidiabetic drugs on AF incidence in Korean patients with type 2 diabetes. Methods: We included 2,515,468 patients with type 2 diabetes from the Korean National Insurance Service database without a history of AF who underwent health check-ups between 2009 and 2012. Newly diagnosed AF incidence was recorded until December 2018 according to the main antidiabetic drug combinations used in the real world. Results: Of the patients included (mean age, 62 ± 11 years; 60 % men), 89,125 were newly diagnosed with AF. Metformin (MET) alone (hazard ratio [HR] 0.959, 95 % CI 0.935–0.985) and MET combination therapy (HR < 1) significantly decreased the risk of AF compared to the no-medication group. The antidiabetic drugs consistently showing a protective effect against AF incidence were MET (HR 0.977, 95 % CI 0.964–0.99) and thiazolidinedione (TZD; HR 0.926, 95 % CI 0.898–0.956), even after adjusting for various factors. Moreover, this protective effect was more remarkable with MET and TZD combination therapy (HR 0.802, 95 % CI 0.754–0.853) than with other drug combinations. In the subgroup analysis, the preventive effect of MET and TZD treatment against AF remained consistent, regardless of age, sex, duration, and diabetes severity. Conclusion: The combination therapy of MET and TZD is the most effective antidiabetic drug for preventing AF in patients with type 2 diabetes.