Dapagliflozin monotherapy in drug-naïve patients with diabetes: a randomized-controlled trial of low-dose range

Diabetes Obes Metab. 2012 Oct;14(10):951-9. doi: 10.1111/j.1463-1326.2012.01659.x. Epub 2012 Jul 24.

Abstract

Aims: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Canada / epidemiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Glucosides / administration & dosage
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • India / epidemiology
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Puerto Rico / epidemiology
  • Russia / epidemiology
  • South Africa / epidemiology
  • Treatment Outcome
  • United States / epidemiology
  • Weight Loss / drug effects

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • dapagliflozin