title: Renal glucose reabsorption inhibitors to treat diabetes.
abstract: Current therapies to reduce hyperglycaemia in type 2 diabetes mellitus (T2DM) mostly involve insulin-dependent mechanisms and lose their effectiveness as pancreatic β-cell function declines. In the kidney, filtered glucose is reabsorbed mainly via the high-capacity, low-affinity sodium glucose cotransporter-2 (SGLT2) at the luminal surface of cells lining the first segment of the proximal tubules. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. In T2DM, the glucosuria produced by SGLT2 inhibitors is associated with weight loss, and mild osmotic diuresis might assist a reduction in blood pressure. The mechanism is independent of insulin and carries a low risk of hypoglycaemia. This review examines the potential of SGLT2 inhibitors as a novel approach to the treatment of hyperglycaemia in T2DM.
authors.affiliation: Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. c.j.bailey@aston.ac.uk
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Bailey
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; D049990:Membrane Transport Modulators; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose