title: Dapagliflozin monotherapy in drug-naïve patients with diabetes: a randomized-controlled trial of low-dose range.
abstract: OBJECTIVE
  Many patients with type 2 diabetes are suboptimally managed with currently available therapies. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has shown efficacy in reducing diabetic hyperglycaemia. This study assessed efficacy of three lower doses in recently diagnosed patients.
  
  
  METHODS
  This phase 3, randomized, double-blind, placebo-controlled study assigned treatment-naïve patients to placebo or dapagliflozin monotherapy (1, 2.5 or 5 mg) daily for 24 weeks. Patients were antidiabetic drug-naïve with inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥7.0 and ≤10.0%]. The primary efficacy endpoint was change in HbA1c from baseline. Secondary endpoints included changes in body weight and fasting plasma glucose (FPG), and proportions achieving HbA1c <7%.
  
  
  RESULTS
  A total of 282 patients with type 2 diabetes were randomly assigned to one of four treatment groups. Baseline characteristics were similar across groups. At week 24, mean HbA1c reduction was significantly greater with dapagliflozin: -0.68% for 1 mg, -0.72% for 2.5 mg, -0.82% for 5 mg, versus 0.02% for placebo (p < 0.0001); compared to mean baseline values of 7.8-8.1%. Mean FPG reduction was significantly greater for all dapagliflozin groups versus placebo (p < 0.02), as was mean weight reduction (p < 0.003). During the treatment period, 19.1% of placebo-treated patients received rescue medication or discontinued because of poor glycaemic control versus 6.9, 4.1 and 5.9% for dapagliflozin 1, 2.5 and 5 mg, respectively. Percentages of patients experiencing ≥1 adverse event were similar across groups.
  
  
  CONCLUSIONS
  Dapagliflozin at doses of 1, 2.5 and 5 mg/day is effective in reducing glycaemic levels and body weight in treatment-naïve patients with type 2 diabetes. Dapagliflozin was generally well tolerated. This insulin-independent mechanism suggests a new treatment for type 2 diabetes.
authors: Life and Health Sciences, Aston University, Birmingham, UK. c.j.bailey@aston.ac.uk
authors: C J
authors: CJ
authors: Bailey
authors: N
authors: N
authors: Iqbal
authors: C
authors: C
authors: T'joen
authors: J F
authors: JF
authors: List
mesh_terms: D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002170:Canada / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005960:Glucosides / Q000008:administration & dosage / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D011647:Puerto Rico / Q000453:epidemiology; D012426:Russia / Q000453:epidemiology; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human; C529054:dapagliflozin