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

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.

• Authors: C J Bailey, N Iqbal, C T'joen, J F List
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 14 Issue 10 Pg. 951-9 (Oct 2012) ISSN: 1463-1326 [Electronic] England
• PMID: 22776824 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

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

Topics

• Benzhydryl Compounds
• Blood Glucose (drug effects, metabolism)
• Canada (epidemiology)
• Diabetes Mellitus, Type 2 (blood, drug therapy, epidemiology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Glucosides (administration & dosage, therapeutic use)
• Glycated Hemoglobin (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)