Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, phase 3 study

Abstract

Objective:

Luseogliflozin – a novel, orally bioavailable, 1-thio-d-glucitol derivative and a selective sodium glucose cotransporter 2 inhibitor – has shown efficacy and tolerability in previous phase 2 studies. This phase 3, randomized, double-blind, placebo-controlled, comparative study aimed to confirm the superiority of 24 week luseogliflozin 2.5 mg monotherapy over placebo in reducing hemoglobin A1c (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods:

Patients with HbA1c levels of 6.9%–10.5% were randomized to receive luseogliflozin 2.5 mg or placebo once daily for 24 weeks (n = 79 in each group). The primary endpoint was change from baseline in HbA1c at end of treatment. Secondary endpoints included change from baseline in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) following a meal tolerance test, body weight, and abdominal circumference. Safety assessments included adverse events (AEs), clinical laboratory tests, and vital signs.

Results:

At the end of treatment, HbA1c was significantly decreased from baseline in the luseogliflozin 2.5 mg group (−0.63%) versus the placebo group (0.13%), with a between-group difference of −0.75% (p < 0.001). Additionally, significant reductions in FPG, PPG, body weight, and abdominal circumference were noted with luseogliflozin compared with placebo (all p < 0.05). Luseogliflozin was well tolerated; there was no significant difference between groups in the incidence of AEs (luseogliflozin, 59.5%; placebo, 57.0%). No AEs led to study drug discontinuation. Most AEs were mild in severity, with no severe AE reported. Limitations of this study include its short study duration and small sample size.

Conclusion:

Luseogliflozin monotherapy for 24 weeks was superior to placebo in reducing HbA1c levels. It also reduced FPG, PPG, body weight, and abdominal circumference and was well tolerated in Japanese patients with T2DM.

Clinical trial registration:

JapicCTI-111661.

Keywords::

• Japanese
• Luseogliflozin
• Monotherapy
• Phase 3 clinical study
• Placebo-controlled
• Sodium glucose cotransporter 2 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. The authors retained full control of the manuscript content.

Declaration of financial/other relationships

Y.S. 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 fund 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. M.U., S.S. and Y.S. are employees of Taisho Pharmaceutical Co. Ltd, which is developing luseogliflozin.

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

Acknowledgments

Medical writing services were provided by Cactus Communications.

Previous presentation: Parts of this study were reported as an abstract and poster (abstract 956) at the 49th Annual Meeting of the European Association for the Study of Diabetes, 23–27 September 2013, Barcelona, Spain; and as an abstract and poster (abstract P-1472) at the International Diabetes Federation 2013 World Diabetes Congress, 2–6 December 2013, Melbourne, Australia.