FDA Approves CV Death Reduction Claim for Empagliflozin in Type 2 Diabetes

The US Food and Drug Administration (FDA) has extended the indication for empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) to include reducing the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

The drug, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, is already approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes.

News of the expanded indication comes following an FDA advisory committee meeting this past summer where members voted narrowly in favor of recommending the new indication. At the time, 12 members of the Endocrinologic and Metabolic Drugs Advisory Committee voted in support of the statement that the data provided substantial evidence in establishing that empagliflozin significantly decreases the risk of cardiovascular mortality, while 11 committee members did not. The panel was unanimous in their belief that the drug did not result in an unacceptable increase in cardiovascular risk.

The FDA decision is based largely on EMPA-REG OUTCOME trial, a large-scale cardiovascular outcomes study required of all new diabetes drugs by the FDA, to show that their drugs do not result in an unacceptable increase in cardiovascular risk.

Presented in 2015 at the European Association for the Study of Diabetes meeting and published simultaneously in the New England Journal of Medicine, the trial showed that treatment with empagliflozin reduced the risk of cardiovascular death, nonfatal stroke, and nonfatal MI by 14% compared with placebo-treated patients receiving standard therapy for glycemic control. In addition, empagliflozin significantly lowered the risks of all-cause and cardiovascular mortality by 32% and 38%, respectively, compared with placebo.

The FDA announcement notes that empagliflozin can cause dehydration and low blood pressure, ketoacidosis, serious urinary tract infection, acute kidney injury and impairment in renal function, and hypoglycemia when used with insulin or insulin secretagogues, vaginal yeast infections, genital mycotic infections, and increased cholesterol.