Why do SGLT2 Inhibitors Act as Cardio-renal Protective even in Non-diabetics?

Abstract

Evidence has emerged as to the cardio-renal protective effect of sodium glucose co-transporter 2 (SGLT2) inhibitors. Recent studies, DAPA‒CKD, DAPA‒HF and EMPEROR-Reduced and EMPEROR-Preserved will extend its clinical indications to heart failure and CKD even in patients without diabetes mellitus. This review anew discusses the presumable pharmacological mode of action with SGLT2 inhibitors in non-diabetics. The putative mechanisms by which SGLT2 inhibitors exert the beneficial effects may be accounted for by salt/water diuresis via SGLT2 and Na/H exchanger 3 inhibition, glucosuria-induced osmotic diuresis, and the subsequent optimization of tubule-glomerular feedback system in the kidney.