Abstract
AIMS/INTRODUCTION: In the present dose-response study, we evaluated the efficacy and safety of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium-dependent glucose cotransporter 2, in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: A total of 361 patients from 39 Japanese centers were randomized to receive either once-daily oral ipragliflozin (12.5, 25, 50 or 100 mg) or a placebo for 12 weeks. RESULTS: All ipragliflozin-treated groups had clinically significant, dose-dependent decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose levels compared with placebo-treated groups. The adjusted mean difference in HbA1c change from baseline to the end of treatment between the placebo and 12.5, 25, 50, and 100 mg ipragliflozin groups were -0.61%, -0.97%, -1.29%, and -1.31%, respectively (P < 0.001). Reductions in HbA1c levels were similar between obese and non-obese patients, and were larger in patients with baseline HbA1c ≥8.4% than in those with HbA1c <8.4%. Furthermore, bodyweight significantly (P < 0.001) and dose-dependently decreased among ipragliflozin-treated groups compared with the placebo group. The incidence of adverse events was similar across all groups. However, mild increases in hematocrit and blood urea nitrogen were found in ipragliflozin treated groups. CONCLUSIONS: Once-daily administration of ipragliflozin was dose-dependently effective in glycemic control without major adverse effects. Ipragliflozin was equally effective between obese and non-obese patients, and led to weight loss in both groups. Ipragliflozin was safe and well-tolerated in Japanese patients with type 2 diabetes mellitus. This trial was registered with ClinicalTrials.gov (no. NCT00621868).