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.
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).



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.



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)0-2hin a mixed-meal tolerance test. No significant between-group differences were observed for C-peptide AUC0-2hor glucagon AUC0-2hafter meals. Incidences of adverse events were 60.0% and 47.1% in the T + C and T + P groups, respectively. No hypoglycaemia was observed.



Canagliflozin administered as add-on therapy to teneligliptin was effective and well tolerated in Japanese T2DM patients.
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi
T
Kadowaki
Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nobuya
N
Inagaki
Mitsubishi Tanabe Pharma Corporation, Sohyaku. Innovative research Division, Tokyo, Japan.
Kazuoki
K
Kondo
Mitsubishi Tanabe Pharma Corporation, Sohyaku. Innovative research Division, Tokyo, Japan.
Kenichi
K
Nishimura
Mitsubishi Tanabe Pharma Corporation, Sohyaku. Innovative research Division, Tokyo, Japan.
Genki
G
Kaneko
Mitsubishi Tanabe Pharma Corporation, Sohyaku. Innovative research Division, Tokyo, Japan.
Nobuko
N
Maruyama
Mitsubishi Tanabe Pharma Corporation, Sohyaku. Innovative research Division, Tokyo, Japan.
Nobuhiro
N
Nakanishi
Mitsubishi Tanabe Pharma Corporation, Ikuyaku. Integrated Division, Tokyo, Japan.
Hiroaki
H
Iijima
Mitsubishi Tanabe Pharma Corporation, Ikuyaku. Integrated Division, Tokyo, Japan.
Yumi
Y
Watanabe
Mitsubishi Tanabe Pharma Corporation, Ikuyaku. Integrated Division, Tokyo, Japan.
Maki
0000-0003-2722-5202
M
Gouda
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000187:drug effects; D000068896:Canagliflozin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage*; D053778:Thiazolidines / Q000008:administration & dosage*; D016896:Treatment Outcome
D001786:Blood Glucose; D002096:C-Peptide; D000068896:Canagliflozin; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D011720:Pyrazoles; D053778:Thiazolidines; C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; C517652:hemoglobin A1c protein, human
canagliflozin; co-transporter 2 inhibitors; dipeptidyl peptidase-4 inhibitors; sodium glucose type 2 diabetes mellitus; teneligliptin