Considering Cardiovascular Risks of Antidiabetic Drugs

A review of current antidiabetic drug treatments available and their individual cardiovascular risk profiles.

Cardiovascular disease (CVD) is the leading cause of death in patients with diabetes, who have double the risk for stroke, heart disease, and death from heart disease compared to people who do not have diabetes.1

While studies have consistently found intensive glycemic control to decrease the risk of microvascular complications, findings regarding its impact on macrovascular complications have been mixed. It has been unclear whether reducing glucose reduces these risks, and there has been concern that it could actually have adverse cardiovascular (CV) effects.1

In 2008, the US Food and Drug Administration (FDA) published a set of recommendations pertaining to the evaluation of CV risk in new medications intended for the treatment of type 2 diabetes .2 The document states that “specifically, this guidance makes recommendations about how to demonstrate that a new antidiabetic therapy to treat type 2 diabetes is not associated with an unacceptable increase in cardiovascular risk.”

One of the newest drugs for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, appears to fit the criteria. In November 2015, research published in the New England Journal of Medicine suggested that it may decrease the risk of death in patients with type 2 diabetes who are at high risk of CV events.3

In this randomized, double-blind, placebo-controlled trial, 7020 adult patients with type 2 diabetes and high CV risk were assigned to 1 of 3 groups that received a placebo or a 10-mg or 25-mg dose of empagliflozin once per day over a median observation time of 3.1 years, in addition to standard care. Primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent myocardial infarction), or nonfatal stroke.3

Results showed that in the combined empagliflozin groups, the primary outcome occurred in 10.5% of patients vs 12.1% in the placebo group (hazard ratio [HR] in the empagliflozin group=0.86; 95.02% confidence interval [CI]: 0.74-0.99; P=.04 for superiority). The empagliflozin group had significantly lower CV-related risk of death (HR=0.62; 95% CI:, 0.49-0.77; P<.001), hospitalization for heart failure (HR= 0.65; 95% CI: 0.50-0.85; P=.002), and death from any cause (HR=0.68; 95% CI: 0.57-0.82, P<.001). The drug is associated with weight loss and decreased blood pressure without increased heart rate, the authors wrote, and it “has favorable effects on markers of arterial stiffness and vascular resistance, visceral adiposity, albuminuria, and plasma urate.”3