The role of kidney in glucose homeostasis--SGLT2 inhibitors, a new approach in diabetes treatment

Expert Rev Clin Pharmacol. 2013 Sep;6(5):519-39. doi: 10.1586/17512433.2013.827399. Epub 2013 Aug 26.

Abstract

The role of the kidney in blood glucose-level regulation was until recently underestimated. Renal gluconeogenesis, renal glucose uptake and tubular glucose reabsorption are the three ways of renal involvement in glucose homeostasis. In the postabsorptive state, 20% of total glucose release is attributed to renal gluconeogenesis. Tubular glucose reabsorption is performed by the combined action of Na⁺/D-glucose SGLTs co-transporters and GLUT-facilitated diffusion glucose transporters. SGLT2 inhibitors are a new family of agents, which occlude the path of SGLT2 glucose reabsorption and cause glucosuria. Efficacy of SGLT2 inhibitors includes reduction of HbA1c, fasting and postprandial blood glucose level and slight body weight and systolic blood pressure decrease. The most common adverse events of them are genital mycotic and urinary tract infections. Dapagliflozin and canagliflozin are the first agents of this class, approved from the European Medicine Agency and FDA, respectively.

Publication types

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

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Canagliflozin
  • Clinical Trials as Topic
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Gluconeogenesis / drug effects
  • Glucose / metabolism*
  • Glucosides / administration & dosage
  • Glucosides / adverse effects
  • Glucosides / therapeutic use
  • Homeostasis / drug effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use
  • Treatment Outcome

Substances

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