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 = 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 −0.36, −0.62, and −0.75% in the 0.5, 2.5, and 5 mg luseogliflozin groups, respectively, versus +0.06% in the placebo group (all P < 0.001). The reductions in FPG and 2 h-PPG in the MTT were also significantly greater in the luseogliflozin groups (all P < 0.01) 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.

Keywords::

• Japanese
• Luseogliflozin
• Monotherapy
• Phase II clinical study
• Placebo
• Sodium glucose cotransporter 2 (SGLT2) inhibitor
• Type 2 diabetes mellitus

Transparency

Declaration of funding

Luseogliflozin is being developed by Taisho Pharmaceutical Co. Ltd. This study was supported by Taisho Pharmaceutical Co. Ltd.

Declaration of financial/other relationships

Y.Se. has disclosed that he has received consultancy fees or lecture fees from Sanofi, Novo Nordisk, Eli Lilly and Company, GlaxoSmithKline, Astellas Pharma, Takeda Pharmaceuticals, Boehringer Ingelheim, Johnson & Johnson, Becton Dickinson and Company, AstraZeneca, and Taisho Pharmaceutical Co. Ltd. T.S. has disclosed that he has received joint research funds from Canon Inc. and consultancy fees from Taisho Pharmaceutical Co. Ltd. A.F. has disclosed that he has received consultancy fees from Taisho Pharmaceutical Co. Ltd. S.S. and Y.Sa. have disclosed that they are employees of Taisho Pharmaceutical Co. Ltd.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Nicholas D. Smith PhD for editorial support.

Previous presentation: Parts of this study were reported as an abstract and poster (abstract 998-P) at the 71st Annual Scientific Sessions of the American Diabetes Association, 24–28 June 2011, San Diego, CA, USA; and as an abstract and oral presentation (abstract 148) at the 47th Annual Meeting of the European Association for the Study of Diabetes (EASD), 12–16 September 2011, Lisbon, Portugal.