Abstract
INTRODUCTION: Maintenance of drug efficacy and safety over the long term is important to investigate for progressive conditions like type 2 diabetes mellitus (T2DM). This study aimed to evaluate whether efficacy of dapagliflozin added to glimepiride observed at 24 weeks was maintained at 48 weeks, and to provide further safety and tolerability data in patients with T2DM. METHODS: This 24-week randomized, double-blind, parallel-group, placebo-controlled trial with a 24-week double-blind extension period enrolled adults whose T2DM was inadequately controlled [glycated hemoglobin (HbA1c) 7.0-10.0%] on sulfonylurea monotherapy. Patients were randomized to placebo (n = 146) or dapagliflozin 2.5 mg (n = 154), 5 mg (n = 145), or 10 mg (n = 151) per day added to open-label glimepiride 4 mg/day. RESULTS: In total, 519 patients (87.1%) completed the study. At 48 weeks, HbA1c adjusted mean changes from baseline for the placebo versus dapagliflozin 2.5/5/10-mg groups were -0.04% versus -0.41%, -0.56% and -0.73%, respectively. There were no meaningful differences in HbA1c changes from baseline from 24 to 48 weeks, indicating that glycemic efficacy was maintained. Improvements in fasting plasma glucose and post-challenge plasma glucose were also observed with dapagliflozin over 48 weeks. Dapagliflozin 2.5/5/10 mg produced sustained reductions in weight (-1.36/-1.54/-2.41 kg) versus placebo (-0.77 kg). Adjusted mean reductions from baseline in systolic blood pressure were also greater than placebo for all dapagliflozin doses. In the placebo versus dapagliflozin groups, serious adverse events were 8.9% versus 8.6-11.0%, hypoglycemic events were 6.8% versus 9.7-11.3%, and events suggestive of genital infection were 1.4% versus 5.2-8.6%. CONCLUSION: Dapagliflozin added to glimepiride improved glycemic control and body weight, with short-term findings maintained during the study's extension period. Therapy was generally well tolerated over 48 weeks; hypoglycemic events and events suggestive of genital infection were reported more often in patients receiving dapagliflozin.