Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus

J Clin Endocrinol Metab. 2010 Jan;95(1):34-42. doi: 10.1210/jc.2009-0473. Epub 2009 Nov 5.


Context: Sodium-glucose cotransporter 2 (SGLT2) expressed in the proximal renal tubules accounts for about 90% of the reabsorption of glucose from tubular fluid. Genetic defects of SGLT2 result in a benign familial renal glucosuria. Pharmacological agents that block SGLT2 are being tested as potential treatment for type 2 diabetes mellitus.

Evidence acquisition: A Pubmed search was used to identify all relevant articles on the physiology of SGLTs as well as published preclinical and clinical experimental studies with SGLT2 inhibitors; a reference search of all retrieved articles was also undertaken.

Evidence synthesis: SGLT2 is almost exclusively expressed in the proximal renal tubules. Preclinical studies with selective SLGT2 inhibitors show dose-dependent glucosuria and lowering of blood glucose in models of type 2 diabetes. Preliminary clinical studies of up to 3-month duration show dose-dependent lowering of glycosylated hemoglobin up to 0.9% along with modest weight loss. Side effects include an increase in genital fungal infection compared to placebo, increased urine volume (300-400 ml/24 h), and evidence of volume depletion consistent with mild diuretic effect.

Conclusion: SGLT2 inhibitors are showing promise as a useful addition to the current therapeutic options in type 2 diabetes mellitus. Results of ongoing phase III clinical trials are awaited and will determine whether the risk-benefit ratio will allow approval of this new class of drug for the management of type 2 diabetes mellitus.

Publication types

  • Evaluation Study
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Drug Design
  • Glucose / metabolism
  • Glycosuria / chemically induced
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Kidney / metabolism
  • Models, Biological
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*


  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucose