News from the FDA/CDC

Empagliflozin first antidiabetes drug to gain cardioprotective indication


Empagliflozin is the first antidiabetes medication to be approved for reducing the risk of cardiovascular death in patients with type 2 diabetes and concomitant cardiovascular disease.

The Food and Drug Administration granted the new indication based on the EMPA-REG OUTCOME study, a postmarketing analysis that found that empagliflozin (Jardiance, Boehringer-Ingelheim) reduced the risk of cardiovascular death by 38% when added to standard-of-care type 2 diabetes therapy.

“This new indication represents a tremendous step forward in our efforts to reduce the impact of cardiovascular disease among adults with type 2 diabetes and established cardiovascular disease,” Paul Fontayne, president and CEO of Boehringer-Ingelheim, said in a press statement. “We believe that this medicine is an important new treatment option for this patient population.”

When empagliflozin was approved for type 2 diabetes in 2014, the FDA required an additional postmarketing study to examine its cardiovascular safety. The 48-month, open-label EMPA-REG enrolled more than 7,000 patients who had type 2 diabetes and a high risk of cardiovascular disease.

The study’s big surprise, however, was not empagliflozin’s safety, but its striking cardioprotective qualities. It reduced by 14% the risk of the primary endpoint, a composite of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction (N Engl J Med. 2015;373:2117-28).

When examined as individual outcomes in a secondary analysis, empagliflozin significantly reduced the risk of cardiovascular death by 38%. However, risk reductions on the other endpoints were not significant. Nevertheless, experts called empagliflozin’s cardiovascular benefit a potential game-changer for the clinical challenge of managing patients with both disorders.

But the drug barely squeaked by its June FDA approval hearing for the cardioprotective indication, receiving a split 12-11 endorsement from the Endocrinologic and Metabolic Drugs Advisory Committee. The major sticking point was that EMPA-REG was a test of empagliflozin’s cardiovascular safety, not its efficacy, and that cardiovascular death was not a prespecified endpoint.

Although there were no significant cardiovascular safety issues, empagliflozin has been associated with hypotension, serious urinary tract infection, acute kidney injury, and genital infections.

“Cardiovascular disease is a leading cause of death in adults with type 2 diabetes mellitus,” Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, wrote in a press statement. “Availability of antidiabetes therapies that can help people live longer by reducing the risk of cardiovascular death is an important advance for adults with type 2 diabetes.”

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