Comparative cardiovascular outcomes of SGLT2 and DPP-4 inhibitors in type 2 diabetes: a nationwide Korean NHIS cohort study

Head-to-head comparisons of sodium–glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors remain limited in East Asian populations. We compared outcomes in Korean adults with type 2 diabetes entering combination oral therapy. Using the Korean National Health Insurance Service database (2013–2023), adults aged ≥ 39 years with newly treated type 2 diabetes between 2015 and 2019 who reached combination therapy of ≥ 2 antidiabetic classes including an SGLT2 or DPP-4 inhibitor, with ≥ 90 consecutive days of prescription coverage, were identified; the primary analysis used a day-90 landmark, with 1:1 matching among patients event-free at that landmark; marginal Cox models with pair-clustered variance were fitted. Among 44,777 matched pairs, SGLT2 inhibitors were associated with a lower risk of the composite of all-cause death, myocardial infarction, or stroke (5-year cumulative incidence 3.42% vs. 4.38%; HR 0.78, 95% CI 0.72–0.84; p < 0.001), driven by all-cause death (2.08% vs. 2.95%; HR 0.69, 0.62–0.76; p < 0.001). Neither stroke (HR 0.90, 0.79–1.04) nor myocardial infarction (HR 1.02, 0.82–1.27) differed. Safety events per 1,000 person-years (DPP-4 inhibitor vs. SGLT2 inhibitor) were: genital infection 34.0 vs. 55.4; acute kidney injury 6.4 vs. 5.0; hypovolaemia 10.8 vs. 10.8; diabetic ketoacidosis 0.71 vs. 0.73. In this nationwide cohort, SGLT2 inhibitors were associated with a lower risk of the composite of all-cause death, myocardial infarction, or stroke, driven mainly by lower all-cause mortality; neither cardiovascular component differed significantly. The associations were consistent in sensitivity analyses and showed moderate robustness in the E-value assessment, and should be interpreted within the limits of observational data.