Efficacy and safety of canagliflozin as add-on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: Results of a 24-week, randomized, double-blind, placebo-controlled trial

Takashi Kadowaki, Nobuya Inagaki, Kazuoki Kondo, Kenichi Nishimura, Genki Kaneko, Nobuko Maruyama, Nobuhiro Nakanishi, Hiroaki Iijima, Yumi Watanabe, Maki Gouda, Takashi Kadowaki, Nobuya Inagaki, Kazuoki Kondo, Kenichi Nishimura, Genki Kaneko, Nobuko Maruyama, Nobuhiro Nakanishi, Hiroaki Iijima, Yumi Watanabe, Maki Gouda

Abstract

Aims: To investigate efficacy and safety of the sodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozin administered as add-on therapy to the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin in patients with type 2 diabetes mellitus (T2DM).

Materials and methods: We conducted a multicentre, randomized, double-blind, placebo-controlled, phase 3 clinical trial in Japanese patients with T2DM who had inadequate glycaemic control with teneligliptin. Patients were randomized to receive teneligliptin 20 mg plus either canagliflozin 100 mg (T + C, n = 70) or placebo (T + P, n = 68) once daily. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. Other endpoints included changes in fasting plasma glucose, body weight, proinsulin/C-peptide ratio, homeostatic model assessment 2-%B and adverse events. Patients also underwent mixed-meal tolerance tests.

Results: The difference between the T + C and T + P groups for HbA1c change from baseline to week 24 was -0.88% (least-squares mean, P < .001). Fasting plasma glucose, body weight and the proinsulin/C-peptide ratio were significantly lower in the T + C group than in the T + P group. Homeostatic model assessment 2-%B improved with T + C compared with T + P. The T + C group exhibited a decrease in the 2-hour postprandial plasma glucose and plasma glucose area under the curve (AUC)0-2h in a mixed-meal tolerance test. No significant between-group differences were observed for C-peptide AUC0-2h or glucagon AUC0-2h after meals. Incidences of adverse events were 60.0% and 47.1% in the T + C and T + P groups, respectively. No hypoglycaemia was observed.

Conclusions: Canagliflozin administered as add-on therapy to teneligliptin was effective and well tolerated in Japanese T2DM patients.

Keywords: canagliflozin; co-transporter 2 inhibitors; dipeptidyl peptidase-4 inhibitors; sodium glucose type 2 diabetes mellitus; teneligliptin.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Time course of change in HbA1c level from baseline in the 24‐week treatment period. Values are reported as LS means ± standard error. LS means by analysis of covariance (factor: treatment group; covariate: baseline value). *P < .001 for T + C vs T + P at all time points. HbA1c, glycated haemoglobin; LOCF, last observation carried forward; LS mean, least squares mean; T + C, teneligliptin + canagliflozin; T + P, teneligliptin + placebo
Figure 2
Figure 2
Effects of T + C vs T + P on the time course of plasma glucose (A), C‐peptide (B) and glucagon (C) during the mixed‐meal tolerance test. Values are reported as means + standard deviation (T + P) or mean – standard deviation (T + C). Numbers of patients: 68 (T + P) and 70 (T + C) at baseline, and 61 (T + P) and 67 (T + C) at week 24. T + C, teneligliptin + canagliflozin; T + P, teneligliptin + placebo

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