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

Year: 2026

Type: article

Abstract: BACKGROUNDS: Despite 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. METHODS: This 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. RESULTS: During 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. CONCLUSIONS: This study showed that SGLT2 inhibitor use was associated with a significantly lower risk of AF than use of thiazolidinediones, DPP-4 inhibitors, and sulfonylureas.

Source: Cardiovascular Diabetology

DOI: 10.1186/s12933-025-03024-9