Role of sodium glucose co-transporter 2 inhibitors in patients with heart failure: an elusive mechanism

Abstract

Heart failure (HF) is a major cause of morbidity and mortality worldwide, and the burden of HF continues to rise. There has been an interest in sodium-glucose co-transporter-2 (SGLT2) inhibitors for their role in reducing HF hospitalizations in pivotal trials. Since these agents were approved by the Food and Drug Administration for the management of diabetes mellitus, multiple small trials and analyses have tried to explain the underlying beneficial mechanisms in HF . In this review, we discuss different mechanisms by which SGLT2 inhibitors play hemodynamic, metabolic, and cellular roles in different HF phenotypes. We also address issues pertaining to the safety of these relatively newer agents.KEY MESSAGESSGLT2 inhibitors are associated with a reduction in HF hospitalizations in both diabetics and non-diabetics.The beneficial role of SGLT2 inhibitors in reducing HF hospitalization is observed among participants with established cardiovascular disease/HF and at-risk population.SGLT2 inhibitors pose an important role in renal protection, another mechanism by which these medications can be helpful in HF patients.

Keywords: Cardiovascular outcomes; diabetes; heart failure; sodium glucose co-transporter 2 inhibitors.

Figure 1.

Mechanism of action of sodium glucose co-transport-2 inhibitors TGF-ß: transforming growth factor-ß; ECM: extracellular matrix; NHE: sodium-proton exchanger; CAM: calcium-calmodulin-dependent kinase II; LV: left ventricular; RAAS: renin–angiotensin–aldosterone system; EPO: erythropoietin.