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

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.