Sodium-glucose Cotransporter 2 Inhibitors: The Impact on Development and Progression of Heart Failure

Background: Available hypoglycemic-agents enable physicians to achieve consistent glycemic-control, but effects on cardiovascular-outcomes have been marginal or questionable. SGLT-2 inhibitors emerged as a novel antidiabetic drug class with remarkable cardiovascular benefits, and significant improvement in the prevention and progression of HF. Objective: The purpose of this article is to critically review the effect of SGLT-2 inhibitors on HFoutcomes and the potential underlying mechanisms. Method: We conducted a thorough review of the literature. The studies addressing the impact of SGLT-2 inhibitors on HF and potential underlying mechanisms were identified. Additionally, we reviewed the references of the identified original papers. Results: The EMPA-REG OUTCOME trial was the first cardiovascular safety study of this drug class that assessed among other outcomes, the impact of SGLT-2 inhibition on HF. Empagliflozin was associated with significant reductions of the risks for hospitalization or death from HF in patients with- and without-HF. Similar benefits were noted from a large-cohort study assessing the effect of SGLT-2 inhibitors on HF-outcomes in real-life. Potential mechanisms include the SGLT-2 inhibitors-induced lowering of blood pressure, the decrease in visceral obesity and the amelioration of arterial stiffness. Improvements of left ventricular mass and diastolic dysfunction may also be implicated in the manifestation of HF-benefits. Lastly, the SGLT-2 inhibitors-related higher ketones bioavailability might offer a better “fuel” to the myocardium. Conclusion: The pleiotropic effects of SGLT-2 inhibitors seem to be translated in significant improvement of HF-related outcomes. On-going trials will provide further information on the impact of these agents in various high- and low-risk populations.