Reno-protective potential of sodium glucose cotransporter-2 (SGLT2) inhibitors: Summary evidence from clinical and real-world data

Type 2 diabetes mellitus is an independent risk factor for renal impairment, developing in due course to end-stage kidney disease (ESKD). Such progressive renal damage is related to an increased predisposition to cardiovascular events and mortality. Even with intensive glycemic control and use of nephro-protective renin angiotensin system (RAS) blockers, rise in the worldwide prevalence of diabetic kidney disease remains tenacious. Identifying drugs with potential to halt progressive renal damage is the pressing priority at present. Sodium glucose cotransporter 2 (SGLT2) inhibitors, by virtue of their glucose-lowering and additional pleotropic effects, such as weight reduction, blood pressure lowering, anti-inflammatory, anti-fibrotic effects etc. are postulated to affect systemic and intrarenal hemodynamic mechanisms in a favorable manner which ultimately contribute to beneficial processes in the kidney. The promising reno-protective efficacy of these drugs is further highlighted by a reduction in development/progression of albuminuria and stabilization of renal function associated with their use. In particular, recent cardiovascular and kidney disease focused outcome trials have effectively demonstrated reduced rates of ESKD and other hard renal end-points, including doubling of serum creatinine, renal transplantation, death due to renal causes etc. with SGLT2 inhibitors. In this review, we dig further deep into the proposed reno-protective benefit furnished by this class of drugs by summarizing the evidence generated from clinical trials and large real-world studies. Current guideline recommendations and probability of reno-protection being influenced by factors, such as diabetic status, baseline renal function, RAS blockade is also explored to discuss their intended use in clinical settings.