Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial

Yasuo Terauchi, Masahiro Tamura, Masayuki Senda, Ryoji Gunji, Kohei Kaku, Yasuo Terauchi, Masahiro Tamura, Masayuki Senda, Ryoji Gunji, Kohei Kaku

Abstract

Aims: To assess the effects of 16 weeks of tofogliflozin (sodium-glucose co-transporter-2 [SGLT2] inhibitor) treatment vs placebo on glycated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor.

Methods: The study comprised a 16-week, multicentre, double-blind, placebo-controlled period and a 36-week extension (NCT02201004). Men and women (aged ≥20 and ≤75 years) with T2DM (HbA1c ≥7.5% and ≤10.5%) were randomized 2:1 to tofogliflozin 20 mg once/day or placebo. The primary endpoint was change in HbA1c from baseline. Insulin reduction was not permitted during this study.

Results: A total of 211 patients were randomized (141 tofogliflozin, 70 placebo). Addition of tofogliflozin to insulin therapy was significantly superior to placebo for lowering HbA1c (-0.59 vs +0.48%; P < .0001), fasting plasma glucose (-27.2 vs +5.3 mg/dL; P < .0001), postprandial plasma glucose (-65.0 vs +3.2 mg/dL; P < 0.0001), serum uric acid (-0.18 vs +0.07 mg/dL; P = .0062), body weight (-1.34 vs +0.03 kg; P < .0001) and daily insulin dose (-1.3 vs -0.2 U, P = .0152). Hypoglycaemia occurred in 30.7% of patients receiving tofogliflozin vs 21.4% for placebo. Two patients treated with tofogliflozin each had a genital or urinary tract infection.

Conclusions: This 16-week double-blind study indicated that, in patients with T2DM whose HbA1c levels were poorly controlled with insulin monotherapy or insulin plus a DPP-4 inhibitor, addition of tofogliflozin was an effective treatment option with an acceptable safety profile.

Keywords: SGLT2 inhibitor; basal insulin (or insulin therapy); glycaemic control; hypoglycaemia; randomized trial; type 2 diabetes.

Conflict of interest statement

Y. T. has received honoraria for speakers bureau from Astellas Pharma Inc., AstraZeneca K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Company Ltd, Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan K.K., Kowa Pharmaceutical Company Ltd., Merck Sharp & Dohme K.K., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Company Ltd; and grants from Astellas Pharma Inc., AstraZeneca K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Company Limited, Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan K.K., Kowa Pharmaceutical Company Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd, Taisho Toyama Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Company Ltd.

M. T. and M. S. are employees of Sanofi K.K. R. G. is an employee of Kowa Company, Ltd.

K. K. is an advisor to, received honoraria for lectures from, and received scholarship grants from Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Sumitomo Dainippon Pharma, Fujifilm Pharma, Kissei Pharmaceutical, Kowa, MSD, Novartis Pharma, Ono Pharmaceutical, Sanofi K.K., Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Taisho Toyama Pharmaceutical and Daiichi Sankyo.

© 2017 Sanofi K.K. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Patient disposition
Figure 2
Figure 2
Change in HbA1c values for tofogliflozin and placebo from baseline to week 16. Values shown are mean ± standard error

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