Efficacy and safety of luseogliflozin monotherapy in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, placebo-controlled, phase II study

Abstract

Objective: Luseogliflozin is a novel sodium glucose cotransporter 2 inhibitor for type 2 diabetes mellitus (T2DM) treatment. An exploratory Phase II study was conducted to assess the efficacy and safety of several doses of luseogliflozin in Japanese T2DM patients. Patients and methods:Japanese T2DM patients aged 20-74 years with hemoglobin A1c (HbA1c) of 6.9-10.5%, fasting plasma glucose (FPG) !126 mg/dL and on diet therapy were randomized in a double-blind manner to receive luseogliflozin (0.5, 2.5, or 5 mg) or placebo once daily for 12 weeks (n ¼ 61, 61, 61, and 56, respectively). The primary endpoint was the change in HbA1c from baseline to end of treatment. Other endpoints included FPG, 2 h postprandial plasma glucose (PPG) in a meal tolerance test (MTT), and body weight. Drug safety was also assessed.Trial registration: Japan Pharmaceutical Information Center (identifier: JapicCTI-090908). Results:Changes in HbA1c from baseline to end of treatment were À0.36, À0.62, and À0.75% in the 0.5, 2.5, and 5 mg luseogliflozin groups, respectively, versus þ0.06% in the placebo group (all P50.001). The reductions in FPG and 2 h-PPG in the MTT were also significantly greater in the luseogliflozin groups (all P50.01) without increases in insulin levels from baseline. Luseogliflozin reduced body weight at all doses. There were no significant differences in the incidences of adverse events among groups. Most adverse events were mild in severity. There were no serious adverse events. Conclusions:Although this was a small-scale study with a short duration, all tested doses of luseogliflozin significantly improved glycemic control, reduced body weight, and were well tolerated in Japanese T2DM patients over the 12-week treatment period.

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

“…In addition, the improvements in glycemic control tended to be greater at luseogliflozin doses of !2.5 mg compared with the lower dose. These effects were consistent with the results of our prior exploratory phase II study 19 in which the changes in HbA1c from baseline to the end of treatment were À0.36, À0.62, and À0.75% in the 0.5, 2.5, and 5 mg luseogliflozin groups, respectively, versus þ0.06% in the placebo group. Therefore, the results of both studies indicate that once-daily treatment with 2.5 mg luseogliflozin shows sufficient glucose-lowering effects in Japanese patients with T2DM.…”

“…In an exploratory phase II study 19 , luseogliflozin monotherapy at doses of 0.5, 2.5, and 5 mg together with ongoing diet therapy for 12 weeks significantly reduced hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2 h postprandial plasma glucose (PPG) compared with placebo. In addition, 2.5 and 5 mg of luseogliflozin significantly reduced body weight compared with placebo.…”

Fifty-two-week long-term clinical study of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise

“…*P< 0.001 (compared to baseline using the one-sample t-test). CI, confidence interval; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; SD, standard deviation ies [6,7,11]. It was also comparable to that observed in a 52-week study of sitagliptin (1.7%), a DPP-4 inhibitor known for its low incidence of hypoglycemia when administered as monotherapy [12].…”

Changes in heart rate in patients with type 2 diabetes mellitus after treatment with luseogliflozin: Subanalysis of placebo‐controlled, double‐blind clinical trials

“…These studies are registered at the Japan Pharmaceutical Information Center (identifier: JapicCTI‐090908, JapicCTI‐101191 and JapicCTI‐111661)2, 3, 4. The major inclusion criteria were as follows: Japanese patients with type 2 diabetes mellitus receiving diet and exercise therapy alone, age ≥20 years and with glycated hemoglobin levels ≥6.9% to ≤10.5%.…”