The U.S. Food and Drug Administration’s (FDA’s) Endocrine and Metabolic Drugs Advisory Committee on June 28 voted 12 – 11 that the results of the EMPA-REG OUTCOME study provided substantial evidence to establish that empagliflozin reduces cardiovascular mortality. All practicing cardiologists on the committee voted ‘yes’.

According to the results of the clinical trial, published in the New England Journal of Medicine, empaglifozin proved superior to placebo in improving glycemic control and reducing cardiovascular events in patients with type-2 diabetes and established cardiovascular disease. The primary outcome of cardiovascular death, nonfatal myocardial infarction (MI), or stroke occurred in 10.5 percent of participants treated with empaglifozin, compared to 12.1 percent of participants receiving a placebo.

The committee’s close vote on the question of whether the study demonstrated a reduction in cardiovascular mortality clearly reflected concerns on the number of indeterminate deaths in clinical trial and the lack of rigor by the sponsor in this area. Additionally, there was substantial discussion amongst panelists regarding the inconsistent treatment of sudden MI within the study. 

Even panelists voting ‘yes’ indicated that did not arrive at their vote easily. Marvin A. Konstam, MD, FACC, a member of today’s panel, wished the FDA “[g]ood luck in figuring out what to do.” Among those who voted ‘no,’ committee members felt that this was the first such drug in its class to make this claim, and it relied on only one study. As such, there was a feeling that it should be held to a higher standard, or at least to the FDA’s typical requirement of two studies to indicate ‘substantial evidence.’

The decision on whether to update the empagliflozin label will now rest with the FDA.

Keywords: United States Food and Drug Administration, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Glucosides, Hypoglycemic Agents, Myocardial Infarction, Outcome Assessment, Health Care, Pharmaceutical Preparations, Stroke

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