Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus

Diabetes Metab Res Rev. 2013 Jul;29(5):347-56. doi: 10.1002/dmrr.2403.

Abstract

Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.

Keywords: glucose reabsorption; sodium-glucose cotransporter 2 inhibitor; type 2 diabetes mellitus.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Therapy, Combination / adverse effects
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism
  • Membrane Transport Modulators / adverse effects
  • Membrane Transport Modulators / pharmacology
  • Membrane Transport Modulators / therapeutic use*
  • Molecular Targeted Therapy*
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Drugs, Investigational
  • Hypoglycemic Agents
  • Membrane Transport Modulators
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors