Possible mechanisms of cardiovascular benefits of SGLT2 inhibitors

The cardiovascular benefit of SGLT2 inhibitors has been clearly shown in several prospective cardiovascular outcome studies with, more particularly, a rapid and very significant reduction of hospitalization for heart failure. The precise mechanisms responsible for the improvement of myocardial function on SGLT2 inhibitors are not yet clarified but several hypotheses may be suggested. SGLT2 inhibitors reduce the ventricular preload and postload via a diuretic effect (osmotic diuresis) and induction of arterial vasodilation. SGLT2 inhibitors increase plasma level of ketone bodies whose bioenergetics properties are superior to those of glucose and of free fatty acids and that could be used as preferred energetic substrates by the myocardium. SGLT2 inhibitors could also have direct effects on the myocardium by inhibiting the Na+/H+ exchanger, by increasing plasma glucagon, which has a positive inotropic effect, by reducing cardiac fibrosis and by decreasing epicardial fat leading to reduced local production of pro-inflammatory adipocytokines which are detrimental to the myocardium. (C) 2019 Elsevier Masson SAS. All rights reserved.