Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, double-blind, placebo-controlled, phase II study

Objectives: Luseogliflozin is a selective sodium glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM). This phase II study was conducted to confirm the efficacy and safety of luseogliflozin monotherapy at doses of up to 10 mg in Japanese patients with T2DM. Patients and methods: Patients with hemoglobin A1c (HbA1c) of 6.9-10.5% on diet therapy were randomized in a double-blind manner to treatment with 1, 2.5, 5, or 10 mg luseogliflozin or placebo for 12 weeks (n=56, 56, 54, 58, and 58, respectively). Trial registration: Japan Pharmaceutical Information Center (identifier: Japic CTI-101191). Main outcome measures: The primary endpoint was the change in HbA1c from baseline to the end of treatment. Other endpoints included fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight. Adverse events were recorded throughout the study. Results: HbA1c decreased significantly at the end of treatment in the 1, 2.5, 5, and 10 mg luseogliflozin groups compared with placebo (-0.29, -0.39, -0.46, and -0.43%, respectively, versus +0.22%; all P<0.001), as did FPG and PPG (all P<0.001). Body weight also decreased significantly in all luseogliflozin groups compared with placebo (all P<0.001). The incidence rates of adverse events (40.0-50.0%) were not significantly different among the five groups. The overall incidence of hypoglycemia was low. Limitations of this study include the short study duration and the relatively small sample size. Conclusions: In Japanese patients with T2DM, luseogliflozin was well tolerated, improved glycemic control, and reduced body weight over 12 weeks of treatment at all tested doses. Doses of >= 2.5 mg achieved similar improvements in glycemic control.