SGLT-2 inhibitors cut heart failure risk for diabetics with, without CVD

Type 2 diabetics who take sodium-glucose co-transporter-2 (SGLT-2) inhibitors experience similar relative reductions in heart failure and mortality regardless of whether they have cardiovascular disease (CVD), according to a subanalysis of the CVD-REAL study published in the Journal of the American College of Cardiology.

Lead author Matthew A. Cavender, MD, MPH, and colleagues studied outcomes of more than 300,000 patients across five countries who were taking either SGLT-2 inhibitors or other glucose-lowering medications. Patients were propensity-matched 1:1 to either group to balance for baseline characteristics. Only 13 percent of the patients had CVD, and average follow-up was about a year for both groups.

Compared to patients taking another glucose-lowering drug, those on SGLT-2 inhibitors demonstrated an identical 44 percent reduction in mortality risk whether they had CVD or not at baseline. The odds of heart failure with SGLT-2 inhibitors were dropped by 28 percent and 39 percent for those with and without CVD, respectively.

“In this analysis, we present stratified data suggesting a similar association (from a relative risk standpoint) in patients with and without established CVD; thus, it is possible the benefits of SGLT-2i could extend to a broad population of patients with T2D (type 2 diabetes),” wrote Cavender, with the University of North Carolina, and coauthors. “This is especially important given that patients with diabetes are typically risk stratified using only clinical variables and history, such as the presence of a prior cardiovascular event.”

Although the relative risk reductions were similar with SGLT-2 inhibitors, the researchers pointed out the lower event rate among those without established CVD means a greater number of those patients would require treatment for a substantial benefit to be apparent.  

Canagliflozin was the most popular SGLT-2 inhibitor in the U.S., while dapagliflozin was widely used in Europe. Insulin was the most common of the other glucose-lowering drugs.

“Although long-term follow-up data from observational studies such as CVD-REAL and ongoing randomized clinical trials are needed to fully understand whether the effects of SGLT-2i are sustained over time, these findings suggest that the cardiovascular benefits of SGLT-2i may not be specific to a single compound, and may extend to a broader population of patients with T2D than previously considered,” wrote the researchers, some of whom are employed by AstraZeneca, the maker of dapagliflozin and a sponsor of the study. “Data from ongoing randomized clinical trials will provide further evidence regarding the cardiovascular benefits of different SGLT-2i, including in patients without established CVD.”

In an accompanying editorial, two Toronto-based physicians said the link between diabetes and early heart failure may help explain why individuals with no known CVD still benefited from SGLT-2 inhibitors.

“Most middle-age persons with type 2 diabetes will have evidence of diastolic dysfunction, even in the absence of a prior ischemic event or known vascular disease,” wrote Michael E. Farkouh, MD, MSc, and Subodh Verma, MD, Phd.

“Although measurements of diastolic or systolic function are not known in this study, it would be reasonable to hypothesize that a large proportion of those without cardiovascular disease already had impaired diastolic function and were predisposed to developing heart failure. SGLT-2i, when used in such individuals, can prevent heart failure, similar to that observed in people with established cardiovascular disease.”