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

• Published in: Diabetes, obesity & metabolism Vol. 14; no. 10; pp. 951 - 959
• Main Authors: Bailey, C. J., Iqbal, N., T'joen, C., List, J. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2012; Wiley Subscription Services, Inc
• Subjects: Antidiabetics; Benzhydryl Compounds; Blood Glucose - drug effects; Blood Glucose - metabolism; Body weight; Canada - epidemiology; dapagliflozin; Diabetes; diabetes mellitus; Diabetes mellitus (non-insulin dependent); 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; Drug dosages; Female; Follow-Up Studies; Glucose transporter; Glucosides - administration & dosage; Glucosides - therapeutic use; glycaemic control; Glycated Hemoglobin A - metabolism; Hemoglobin; Humans; Hyperglycemia; India - epidemiology; Male; Mexico - epidemiology; Middle Aged; Placebos; Puerto Rico - epidemiology; Russia - epidemiology; SGLT2; sodium-glucose co-transporter 2; South Africa - epidemiology; Treatment Outcome; type 2 diabetes; United States - epidemiology; Weight Loss - drug effects; Canada; Puerto Rico; United States; Mexico; South Africa; India; Russia
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2012.01659.x

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.