The effect of empagliflozin on the total burden of cardiovascular and hospitalization events in the Asian and non-Asian populations of the EMPA-REG OUTCOME trial of patients with type 2 diabetes and cardiovascular disease

Aims The sodium-glucose co-transporter 2 inhibitor empagliflozin reduced the total burden of cardiovascular, mortality, and all-cause hospitalization events, including first and recurrent events, in EMPA-REG OUTCOME participants with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD). We investigated the effect of empagliflozin on the total burden of cardiovascular and hospitalization events in Asian participants. Materials and methods Participants were randomized to empagliflozin 10 mg, 25 mg or placebo plus standard of care. The primary and key secondary outcomes were the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke and the primary outcome plus hospitalization for unstable angina, respectively. The effect of pooled empagliflozin versus placebo on total (first plus recurrent) cardiovascular and hospitalization events was analysed using a negative binomial model that preserves randomization and accounts for within-patient correlation of multiple events. We analysed Asian versus non-Asian EMPA-REG OUTCOME population subgroups post hoc. Results Among 1517 Asian participants, empagliflozin reduced the relative risk of total events of the primary outcome by 39% versus placebo [rate ratio (95% confidence interval): 0.61 (0.43, 0.89)], the key secondary outcome by 33% [0.67 (0.48, 0.93)], the composite of cardiovascular death (excluding fatal stroke) and hospitalization for heart failure by 43% [0.57 (0.33, 0.996)], and all-cause hospitalization by 21% [0.79 (0.65, 0.97)]. The effects of empagliflozin were consistent between Asian and non-Asian populations (treatment-by-subgroup interaction p > .05). Conclusions Empagliflozin reduced the total burden of cardiovascular and hospitalization events in Asian and non-Asian EMPA-REG OUTCOME participants with T2D and established ASCVD, consistent with the overall trial population.