Efficacy and safety of canagliflozin as add-on therapy to a glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week, open-label, phase IV study

Shin-Ichi Harashima, Nobuya Inagaki, Kazuoki Kondo, Nobuko Maruyama, Makiko Otsuka, Yutaka Kawaguchi, Yumi Watanabe, Shin-Ichi Harashima, Nobuya Inagaki, Kazuoki Kondo, Nobuko Maruyama, Makiko Otsuka, Yutaka Kawaguchi, Yumi Watanabe

Abstract

Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are antihyperglycaemic agents with weight-lowering effects. The efficacy and safety of the SGLT2 inhibitor canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control with a GLP-1RA (≥12 weeks) were evaluated in this phase IV study. Patients received canagliflozin 100 mg once daily for 52 weeks. Efficacy endpoints included change in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and HDL cholesterol from baseline to week 52. Safety endpoints included adverse events (AEs), hypoglycaemia and laboratory tests. Of the 71 patients treated with canagliflozin, 63 completed the study. At 52 weeks, HbA1c was significantly reduced from baseline (-0.70%; paired t test, P < .001). Significant changes were also observed in FPG (-34.7 mg/dL), body weight (-4.46%), SBP (-7.90 mm Hg), and HDL cholesterol (7.60%; all P < .001). The incidence of AEs, adverse drug reactions and hypoglycaemia was 71.8%, 32.4% and 9.9%, respectively. All hypoglycaemic events were mild. These findings suggest that the long-term combination of canagliflozin with a GLP-1RA is effective and well tolerated in Japanese patients with T2DM.

Keywords: GLP-1 receptor agonist; SGLT2 inhibitor; canagliflozin; phase IV; type 2 diabetes.

Conflict of interest statement

S.H. has received consulting fees and/or speakers' bureau fees from Eli Lilly Japan KK, Mitsubishi Tanabe Pharma Corp., MSD KK, Novo Nordisk Pharma Ltd and Sanofi KK. N.I. has received consulting fees and/or speakers' bureau fees from Astellas Pharma Inc., MSD KK, Nippon Boehringer Ingelheim Co., Ltd, Sanofi KK and Takeda Pharmaceutical Co., Ltd, research support from AstraZeneca KK, Daiichi Sankyo Co., Ltd, Eli Lilly Japan KK, MSD KK and Mitsubishi Tanabe Pharma Corp., and scholarship grants from Astellas Pharma Inc., AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., MSD KK, Mitsubishi Tanabe Pharma Corp., Nippon Boehringer Ingelheim Co., Ltd, Novartis Pharma KK, Novo Nordisk Pharma Ltd, Ono Pharmaceutical Co., Ltd, Pfizer Japan Inc., Sanwa Kagaku Kenkyusho Co., Ltd, Sanofi KK, Sumitomo Dainippon Pharma Co., Ltd, Takeda Pharmaceutical Co., Ltd and Taisho Toyama Pharmaceutical Co., Ltd. K.K., N.M., M.O., Y.K. and Y.W. are employees of Mitsubishi Tanabe Pharma Corp.

© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
A, Change in glycated haemoglobin (HbA1c). B, Change in fasting plasma glucose. C, Percentage change in body weight. D, Change in systolic blood pressure over time (full analysis set). Data represent means ±95% confidence intervals. W0 = first day of the treatment period; WX = week X of the treatment period. *HbA1c(mmol/mol) = 10.93 × NGSP(%) — 23.52. Plasma glucose conversion factor: 1 mg/dL = 0.0555 mmol/L. *P < .01; **P < .001

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