Diabetes Drug May Stop Progression of HF

A recent proposal indicated that sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial to patients with heart failure (HF) with or without diabetes.

According to the researchers, SGLT2 inhibitors are the only class of glucose-lowering agents that have been reported to decrease the risk of cardiovascular events by reducing the risk of the development or progression of HF. Specifically, the inhibitor emphagliflozin has been shown to prevent fatal and nonfatal HF events in diabetic patients, but did not reduce the risk of myocardial infarction or stroke.
______________________________________________________________________________________________

RELATED CONTENT
Statins, Omega-3 Combination May Reduce Heart Failure Risk in Men
Diabetes Influences Outcomes in Chronic Heart Failure
______________________________________________________________________________________________

SGLT2 inhibitors have been shown to benefit the kidneys, the researchers noted. The activity of the sodium-hydrogen exchanger is significantly increased in patients with HF, which may cause resistance to diuretics and endogenous natriuretic peptides. However, this effect is mitigated by SGLT2, which functionally interacts with the sodium-hydrogen exchanger. The ability of spironolactone in particular to inhibit the sodium-hydrogen exchange mechanism may also benefit patients with HF with either a reduced or a preserved ejection fraction.

In the heart, empagliflozin appears to inhibit sodium-hydrogen exchange, which may help reduce cardiac injury, hypertrophy, fibrosis, remodeling, and systolic dysfunction. SGLT2 inhibitors have also been shown to improve renal function and to reduce blood pressure, body weight, and fluid retention, potentially mitigating the major pathophysiological derangements of HF and a preserved ejection.

“The benefits of SGLT2 inhibitors in heart failure may be mediated by the inhibition of sodium-hydrogen exchange rather than the effect on glucose reabsorption,” the researchers concluded. “This hypothesis has important implications for the design and analysis of large-scale outcomes trials involving diabetic or nondiabetic patients with chronic heart failure.”

—Christina Vogt

Reference:

Packer M, Anker SD, Butler J, Filippatos G, Zannad F. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action [Published online August 2, 2017]. JAMA Cardiol. doi:10.1001/jamacardio.2017.2275.