Comparison of ischemic cardiovascular events between dapagliflozin and empagliflozin in combination with metformin: A nationwide population-based cohort study

Abstract

The comparative effectiveness of individual sodium–glucose cotransporter-2 inhibitors (SGLT-2is) in preventing ischemic cardiovascular disease (CVD) remains uncertain. Thus, this study compared the incidence of ischemic CVD events in patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin or empagliflozin in combination with metformin. This retrospective cohort study analyzed national claims data from the Korean National Health Insurance Service. Patients with T2DM who received dapagliflozin or empagliflozin, combined with metformin, between 2014 and 2019 were included. The primary outcome was composite ischemic CVD events, defined as myocardial infarction, ischemic stroke, or coronary revascularization. Secondary outcomes included each component of composite ischemic CVD events, unstable angina, and all-cause mortality. Hazard ratios (HRs) and confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for covariates in three stepwise models: Model 1 (age and sex), Model 2 (Model 1 variables plus patient characteristics), and Model 3 (Model 2 variables plus clinical parameters). In Model 3, after full adjustment for systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, and serum creatinine, no significant difference was observed in the incidence of composite ischemic CVD events between dapagliflozin and empagliflozin when each was used in combination with metformin (adjusted HR 0.50, 95% CI: 0.24–1.03). Additionally, no significant differences were observed in individual components of composite ischemic CVD events, unstable angina, and all-cause mortality. These real-world findings may help in selecting an SGLT-2is subtype for CVD prevention in Asian patients with T2DM.