Can SGLT2 Inhibitors Prevent Heart Failure in a Broad Population?

Mary Caffrey

A study of nearly 365,000 patients taking medication for type 2 diabetes (T2D) shows that sodium glucose co-transporter-2 (SGLT2) inhibitors outperform other treatments for the disease in key ways—and may help prevent heart failure in patients not yet diagnosed.
 
Results from the study, called CVD-REAL, were presented Sunday at the 66th Scientific Session of the American College of Cardiology (ACC). The study, which covered patients from the United States and 5 European countries, examined some questions left unanswered by the EMPA-REG OUTCOME study, which was the first cardiovascular outcomes trial (CVOT) that did not merely find that a T2D therapy was safe, but that it could offer cardioprotective benefits and reduce deaths.

But because EMPA-REG OUTCOME was a safety trial required by the FDA, it studied high-risk patients, and it only examined 1 drug, empagliflozin (Jardiance). In an interview with The American Journal of Managed Care, AstraZeneca's Jim McDermott, vice president for Medical Affairs, Diabetes, said CVD-REAL is designed to ask whether the effects on heart failure are a class effect for all SGLT2 inhibitors, if these effects could be applied to a broad population, and “if they can be demonstrated in a real-world environment. AstraZeneca funded the study.

Researchers gathered data from patients taking all 3 approved therapies: dapagliflozin (Farxiga) from AstraZeneca; canagliflozin (Invokana) from Janssen; and empagliflozin from Boehringer-Ingelheim and Eli Lilly. They also matched data from patients taking other glucose-lowering therapies. Compared with other T2D drugs, the SGLT2 inhibitor class:
Researchers also computed a composite endpoint of hospitalization for heart failure and death from any cause, and found that SGLT2s inhibitors reduced this by 46%, compared with other T2D therapies.

SGLT2 inhibitors work through a unique mechanism of action, which causes excess blood glucose to be expelled through urine. McDermott said this mechanism has been shown to have a diuretic effect that positively affects blood pressure (and has been shown to help patients lose weight), although this is not well-understood.

EMPA-REG OUTCOME raised the curtain on potential new benefits that CVD-REAL sought to explore. Could SGLT2 inhibitors not only treat diabetes, but also prevent heart failure in these patients?

Mikhail Kosiborod, MD, the study's lead author and a cardiologist at St. Luke's Health System in Kansas City, Missouri, said in his presentation that the results suggest a “heart failure prevention signal,â€
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