Atherothrombotic Outcomes After Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes: A Territory-Wide Retrospective Cohort Study

Abstract

BACKGROUND: This study compared the risks of atherothrombotic major adverse cardiovascular events in patients with type 2 diabetes taking SGLT2 (sodium-glucose cotransporter 2) inhibitors to those taking DPP-4 (dipeptidyl peptidase-4) inhibitors. METHODS AND RESULTS: All adult patients (≥18 years of age) with type 2 diabetes and newly prescribed with SGLT2 inhibitors or DPP-4 inhibitors across all public hospitals in Hong Kong between January 2015 and December 2019 were included. Patients were propensity matched in a 1:1 ratio using a caliper distance of 0.2 without replacement. The primary outcome was atherothrombotic major adverse cardiovascular events as a composite outcome of cardiovascular mortality, nonfatal stroke, and nonfatal myocardial infarction. Time-to-first event analysis was conducted using a univariable Cox proportional hazards model. Primary and secondary analyses were repeated using stabilized inverse probability weighting and propensity score adjustment in the complete case cohort. A total of 20 642 patients (10 321 SGLT2 inhibitors versus 10 321 DPP-4 inhibitors) were included in the final analysis. The mean age was 59±11 years, and 13 142 (63.7%) were men. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with a significant reduction in atherothrombotic major adverse cardiovascular events (453 [4.4%] versus 719 [7.0%]; hazard ratio, 0.64 [95% CI, 0.57–0.72]; P<0.001) compared with DPP-4 inhibitors. SGLT2 inhibitors were independently associated with reduced all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and incident dialysis (all P values <0.001). CONCLUSIONS: SGLT2 inhibitors in patients with diabetes were independently associated with reduction in atherothrombotic major adverse cardiovascular events, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and incident dialysis, compared with DPP-4 inhibitors.