The prevalence of type 2 diabetes is increasing rapidly and represents a major risk factor for cardiovascular disease. Although glycemic control has been shown to reduce microvascular complications, the effect of glycemic control on macrovascular disease is more limited. Furthermore, some glucose lowering drugs have been associated with worse cardiovascular outcomes. Accordingly, ensuring the cardiovascular safety of new diabetic therapies is important. Empaglifozin is one of the first in a new class of drugs that lowers serum glucose levels by decreasing renal glucose reabsorption. In this study of 7020 patients at high risk of cardiovascular events, patients were randomized to one of two doses of empagliflozin (10 mg or 25 mg) or placebo, as well as standard guideline based diabetic therapy. The primary outcome was a composite of major adverse cardiovascular events or cardiovascular death. Although powered as a non-inferiority study, empaglifozin demonstrated statistical superiority as add-on diabetic therapy, significantly reducing the incidence of the primary end-point (10.5% vs. 12.1%, HR 0.86; 95% CI, 0.74 to 0.99; P=0.04 for superiority), including a significant reduction in the risk of death (5.7% and 8.3%, respectively; 32% relative risk reduction). Use of empaglifozin increased the rates of genital infection (although UTI rates were similar), presumably secondary to the increased amount of glucose present in urine. No other adverse events were increased with use of empaglifozin.
In this large cardiovascular safety study, the novel oral hypoglycemic agent empagliflozin not only demonstrated an excellent safety profile, but also marked reductions in cardiovascular events and all-cause mortality. These data may reflect a major advancement in management of hyperglycemia to reduce cardiovascular risk.
Summarized by Hussain Contractor and Steven M. Bradley
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Sep 17. [Epub ahead of print]