title: Dapagliflozin for the treatment of type 2 diabetes.
abstract: OBJECTIVE
  To review the literature and describe the pharmacologic, pharmacokinetic, and pharmacodynamic properties; clinical safety; and efficacy of dapagliflozin, a new drug currently under review by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes.
  
  
  METHODS
  A MEDLINE (1995-November 2011) and ClinicalTrials.gov search was conducted using the terms dapagliflozin, sodium-glucose cotransporter 2 inhibitor, and SGLT2 inhibitor. Reference citations from publications identified were also reviewed.
  
  
  METHODS
  All English-language studies, including abstracts, evaluating dapagliflozin use in humans were included in this review.
  
  
  RESULTS
  Dapagliflozin is the first-in-class oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that represents a new potential therapeutic option for the treatment of type 2 diabetes mellitus. Its mechanism of action is insulin- and insulin-sensitivity independent. Preliminary data suggest that dapagliflozin decreases hemoglobin A(1c), fasting plasma glucose, and postprandial plasma glucose, while also promoting weight loss. In Phase 1, 2, and 3 clinical trials, dapagliflozin has exhibited a safety and tolerability profile similar to that of placebo.
  
  
  CONCLUSIONS
  Dapagliflozin is a novel oral antihyperglycemic agent that has demonstrated promise as monotherapy and as synergistic combination therapy with currently available agents in Phase 3 clinical trials. On January 19, 2012, the FDA issued a complete response letter to AstraZeneca and Bristol-Myers Squibb regarding the new drug application for dapagliflozin. The FDA is requesting additional clinical data-from ongoing studies and potentially new clinical trials-to better describe the risk-benefit profile of the drug. Both manufacturers remain committed to the development of dapagliflozin, and there are currently 8 Phase 3 trials ongoing. Dapagliflozin has the potential to be the next new oral agent in the diabetes drug armamentarium.
authors.affiliation: University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. sarah.anderson@ucdenver.edu
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Anderson
authors.forename: Joel C
authors.initials: JC
authors.lastname: Marrs
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000187:drug effects; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin