Abstract
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.