According to the recently published findings of the EMPA-REG OUTCOME trial, empagliflozin caused a relative reduction of 38 percent in cardiovascular (CV) death in type 2 diabetes (T2D) patients who are at high risk for CV events. [N Eng J Med 2015;Doi:10.1056/NEJMoa1504720]

The trial also showed a relative risk reduction of more than 30 percent for both hospitalization due to heart failure and all-cause mortality, said lead investigator, Dr. Bernard Zinman, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Canada. Additionally, empagliflozin—a sodium glucose cotransporter-2 (SGLT-2) inhibitor—reduced the risk for non-fatal myocardial infarction (MI), non-fatal stroke and CV death by 14 percent, he said.

The mechanism behind the reduction in CV death and all-cause mortality is unclear, but Zinman suggested it could be due to empagliflozin’s haemodynamic effects. This is because the benefit of mortality risk reduction occurred very early in the study and generally, atherosclerosis- or hyperglycaemia-related mortality risk reduction does not appear that early, he explained.

Similar to the findings of antecedent studies, the trial found empagliflozin to be safe for long-term use, said Zinman. The incidence of genital infections, a known side effect of empagliflozin, was higher compared to the control group but there was no increase in other adverse events such as diabetic ketoacidosis, acute renal failure and bone fracture.

A total of 7,020 T2D patients from 42 countries participated in the study. All the participants had established CV disease and their CV risk factors were well treated using pharmacological agents. In the study, they were randomized to receive either 10 mg or 25 mg of empagliflozin once daily, or placebo, on top of standard care.

Diabetes is a major risk factor for CV disease and the concurrent existence of both T2D and CV disease increases mortality risk. As diabetic patients have to undergo lifelong treatment with antidiabetic drugs, it is vital to understand the CV safety profile of the drugs. Thus, in 2008, the USA Food and Drug Administration (FDA) issued a new recommendation for novel antidiabetic drugs to undergo CV safety studies. Prior to the EMPA-REG Outcome study, no antidiabetic drug had been found to be able to reduce the risk of CV events.