A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors

Cell Metab. 2021 Apr 6;33(4):732-739. doi: 10.1016/j.cmet.2021.02.016. Epub 2021 Mar 9.


Sodium glucose co-transporter (SGLT) 2 inhibitors reduce the risk of kidney failure in patients with and without type 2 diabetes (T2D). Although the precise underlying mechanisms for these nephroprotective effects are incompletely understood, various hypotheses have been proposed including reductions in intraglomerular pressure through restoration of tubuloglomerular feedback, blood pressure reduction and favorable effects on vascular function, reduction in tubular workload and hypoxia, and metabolic effects resulting in increased autophagy. Here, we review these mechanisms, which may also explain the beneficial effects of SGLT2 inhibitors on kidney function in patients without T2D.

Keywords: chronic kidney disease; nephropathy; sodium glucose co-transporter 2 inhibitors; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / pathology
  • Humans
  • Hypoxia
  • Kidney / drug effects*
  • Kidney / metabolism
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / etiology
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Sodium-Hydrogen Exchanger 3 / metabolism
  • Vasoconstriction / drug effects


  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium-Hydrogen Exchanger 3