Sodium glucose cotransporter 2 and the diabetic kidney

Curr Opin Nephrol Hypertens. 2013 Jan;22(1):113-9. doi: 10.1097/MNH.0b013e32835a17ae.

Abstract

Purpose of review: Reabsorption of glucose in the proximal tubule occurs predominantly via the sodium glucose cotransporter 2 (SGLT2). There has been intense interest in this transporter as a number of SGLT2 inhibitors have entered clinical development. SGLT2 inhibitors act to lower plasma glucose by promoting glycosuria and this review aims to outline the effect on the diabetic kidney of this hypoglycaemic agent.

Recent findings: This review provides an overview of recent findings in this area: the transcriptional control of SGLT2 expression in human proximal tubular cells implicates a number of cytokines in the alteration of SGLT2 expression; experimental data show that SGLT2 inhibition may correct early detrimental effects of diabetes by reducing proximal tubular sodium and glucose transport, suggesting a possible renoprotective effect independent of the glucose lowering effects of these agents; and the nonglycaemic effects of SGLT2 inhibitors may have an impact on renal outcomes.

Summary: The available clinical evidence shows consistent reduction in glycaemic parameters and some evidence suggests additional effects including weight loss and mild blood pressure reduction. There are some side effects that warrant further investigation and establishing whether SGLT2 inhibition provides a renal benefit relies on future long-term studies with specific renal end-points.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Canagliflozin
  • Diabetes Mellitus / drug therapy
  • Diabetic Nephropathies / metabolism*
  • Glucose / metabolism
  • Glucosides / therapeutic use
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Kidney Tubules, Proximal / metabolism*
  • Sodium-Glucose Transporter 2 / genetics
  • Sodium-Glucose Transporter 2 / metabolism*
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiophenes / therapeutic use

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • Canagliflozin
  • dapagliflozin
  • Glucose