title: The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors.
abstract: OBJECTIVE
  A novel class of antidiabetic drugs - SGLT2 (Na(+) /glucose cotransporter type 2) inhibitors - target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds.
  
  
  METHODS
  Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates.
  
  
  CONCLUSIONS
  Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic β-cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy-limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT2 inhibitors are a novel approach.
  
  
  CONCLUSIONS
  A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0·4-1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men.
authors.affiliation: Temple University School of Pharmacy, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cangoz
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Chang
authors.forename: S J
authors.initials: SJ
authors.lastname: Chempakaseril
authors.forename: R C
authors.initials: RC
authors.lastname: Guduru
authors.forename: L M
authors.initials: LM
authors.lastname: Huynh
authors.forename: J S
authors.initials: JS
authors.lastname: John
authors.forename: S T
authors.initials: ST
authors.lastname: John
authors.forename: M E
authors.initials: ME
authors.lastname: Joseph
authors.forename: R
authors.initials: R
authors.lastname: Judge
authors.forename: R
authors.initials: R
authors.lastname: Kimmey
authors.forename: K
authors.initials: K
authors.lastname: Kudratov
authors.forename: P J
authors.initials: PJ
authors.lastname: Lee
authors.forename: I C
authors.initials: IC
authors.lastname: Madhani
authors.forename: P J
authors.initials: PJ
authors.lastname: Shim
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Ruchalski
authors.forename: R B
authors.initials: RB
authors.lastname: Raffa
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
keywords: diabetes; inhibitor; pharmacotherapy; sodium/glucose transport