Renal protection by sodium-glucose cotransporter 2 inhibitors and its underlying mechanisms in diabetic kidney disease.

AIM: Diabetic kidney disease (DKD) is the most frequent cause of mortality and morbidity, leading a global health burden. This review will focus on the potential therapeutic interventions using Sodium-glucose cotransporter-2 (SGLT2) inhibitors that could prevent the development and progression of DKD.

RESULTS: SGLT2 inhibitors have been widely used as anti-diabetic drugs. Recent clinical studies have demonstrated that these drugs, which improve glycemic control and hypertension and decrease body weight, decrease the risk of renal function impairment and heart failure in patients with type 2 diabetes. With regard to long-term clinical outcomes, the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME), the EMPA-REG Renal OUTCOME, and the CANagliflozin cardioVascular Assessment Study (CANVAS) program which have been integrated from CANVAS and CANVAS-Renal (CANVAS-R) trials reported significant risk reductions in primary combined major adverse cardiovascular events. Furthermore, regarding renal outcomes, the EMPA-REG Renal OUTCOME and CANVAS program clearly showed improvements in renal outcomes, including decreases in albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy.

CONCLUSIONS: Potential mechanisms of SGLT2 inhibitors related to renoprotection can be divided into two categories: hemodynamic actions and metabolic actions.