Empagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in routine care in East Asia: Results from the EMPRISE study

AIMS/INTRODUCTION: The EMPA‐REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium‐glucose cotransporter‐2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all‐cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries. MATERIALS AND METHODS: The study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase‐4 inhibitors (DPP‐4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score‐matched (1:1) ‘as‐treated’ analyses comparing the risk of cardiovascular outcomes and all‐cause mortality between empagliflozin and DPP‐4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta‐analysis models comparing both empagliflozin and SGLT2i with DPP‐4i use, respectively. Intention‐to‐treat and subgroup analyses in patients with/without cardiovascular disease and in patients receiving 10 mg empagliflozin were performed. RESULTS: The study included 28,712 and 70,233 matched patient pairs for empagliflozin/DPP‐4i and SGLT2i/DPP‐4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all‐cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67–0.86) and SGLT2i (0.71, 0.65–0.77); (ii) combined myocardial infarction, stroke, and all‐cause mortality was also lower with empagliflozin (0.74, 0.61–0.88) and SGLT2i (0.69, 0.60–0.78) compared to DPP‐4i. The intention‐to‐treat and three subgroup analyses were consistent with results of the main analyses. CONCLUSIONS: The results suggest that both empagliflozin and SGLT2i compared with DPP‐4i are associated with a lower risk of cardiovascular events and all‐cause mortality in routine clinical care in East Asia.