Table 3:

Overview of Potential Mechanism of Beneficial Cardiovascular Effects of SGLT2 Inhibitors

Conceptual Model of Heart Failure	Mechanism of action
Cardiorenal	Stimulation of natriuresis
	Stimulation of osmotic diuresis
	Decreased tubulo-glomerular feedback
Cardiocirculatory	Improved systolic and diastolic function
	Improved cardiac filling conditions secondary to reductions in preload and afterload
	Inhibition of cardiac fibrosis
	Increased cardiac output, increased coronary blood flow mediated by increased levels of circulating glucagon
	Improved myocardial energetics
Neurohormonal	Decreased central nervous system sympathetic nervous activity
Other	Reduction in myocardial CaM kinase II activity
	Increased erythropoietin
	Increased circulating proangiogenic progenitor cells
	Inhibition of cardiac myocyte Na+/H exchanger
	Improved endothelial function
	Increased mitophagy/autophagy

(Modified from Lam CSP et al. SGLT2 Inhibitors in heart failure: Current management, unmet needs, and therapeutic prospects. Journal of the American Heart Association. 2019;8:e013389).