Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes

The effects of empaglif lozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empaglif lozin or placebo once daily. The primary composite outcome was death from cardiovascu - lar causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empaglif lozin group versus the placebo group. The key secondary compos - ite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empa - glif lozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empaglif lozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empaglif lozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empaglif lozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empaglif lozin, as compared with placebo, had a lower rate of the primary com - posite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.)

The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.