FDA/CDC

SGLT2 inhibitor ertugliflozin shows no CV death or renal benefit


 

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

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