Efficacy and safety of canagliflozin as add‐on therapy to teneligliptin in J apanese patients with type 2 diabetes mellitus: R esults of a 24‐week, randomized, double‐blind, placebo‐controlled trial

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 J apanese 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 AUC 0 ‐2h or glucagon AUC 0 ‐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 J apanese T2DM patients.