Comparative effects of second-line oral antidiabetic medications on atrial fibrillation risk in patients with type 2 diabetes: a nationwide retrospective cohort study

Abstract

BackgroundsDespite numerous studies investigating the effects of antidiabetic medications on cardiovascular outcomes, the optimal second-line oral antidiabetic medication for atrial fibrillation (AF) prevention remains unclear. This study aims to compare the effects of second-line oral antidiabetic medications including sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, on the risk of incident AF in patients with type 2 diabetes.MethodsThis retrospective study analyzed data from the National Health Insurance Service data on adults with type 2 diabetes who simultaneously initiated metformin and second-line oral antidiabetic medication (SGLT2 inhibitors, thiazolidinediones, DPP-4 inhibitors, or sulfonylureas) between September 2014 and December 2017. Exact matching by sex and age categories was conducted in a 1:1:5:5 ratio corresponding to SGLT2 inhibitor, thiazolidinedione, DPP-4 inhibitor, and sulfonylurea users, with inverse probability of treatment weighting used to balance the baseline characteristics. The primary outcome was incident AF, which was analyzed using a Fine-Gray model treating all-cause mortality as a competing risk.ResultsDuring a mean follow-up of 6.2 years, 774 cases of AF occurred among the 36,744 participants (mean age 55.3 years; 33.6% female). Compared with SGLT2 inhibitors, the risk of AF was significantly higher in patients using thiazolidinediones (subdistribution hazard ratio [SHR], 1.22; 95% confidence interval [CI], 1.09-1.36), DPP-4 inhibitor (SHR, 1.14; 95% CI, 1.02-1.28), and sulfonylureas (SHR, 1.20; 95% CI, 1.07-1.34). However, pairwise comparisons among thiazolidinediones, DPP-4 inhibitors, and sulfonylureas revealed no significant differences in AF risk. Subgroup analyses revealed significant effect modifications according to age, hypertension status, and renal function.ConclusionsThis study showed that SGLT2 inhibitor use was associated with a significantly lower risk of AF than use of thiazolidinediones, DPP-4 inhibitors, and sulfonylureas.