Clinical pharmacology of SGLT-2 inhibitors in heart failure

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a class of oral antiglycemic agents that have emerged as a new therapeutic strategy for heart failure (HF) with reduced ejection fraction (HFrEF) and, potentially, for HF with preserved ejection fraction (HFpEF). AREAS COVERED: Ongoing efforts to clarify the exact mechanisms of action of SGLT2 inhibitors (SGLT2i) reveal that glycosuria and osmotic diuresis, resulting from the blockade of renal receptors, is not the sole pathophysiological mechanism. Nevertheless, the underlying mechanisms, accounting for their cardiovascular beneficial effects which have been clearly demonstrated in clinical trials, remain unclear. The aim of this review is to summarize the primary outcomes of large-scale studies regarding the use of SGLT2i in HF and provide an overview of the potential pathways involved in the SGLT2i-mediated cardioprotection. EXPERT OPINION: SGLT2i exhibit favorable pleiotropic effects, which extend beyond their primary indication as pharmaceutical agents intended for glycemic control. Given their unique pathophysiological profile, these agents have revolutionized the management of HF, while in the near future, it is possible that evolving research in the field may unfold further perspectives on their potential use in the treatment of other chronic conditions.