Premium
Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin
Author(s) -
Rodbard H. W.,
Seufert J.,
Aggarwal N.,
Cao A.,
Fung A.,
Pfeifer M.,
Alba M.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12684
Subject(s) - canagliflozin , sitagliptin , metformin , medicine , sitagliptin phosphate , type 2 diabetes mellitus , type 2 diabetes , diabetes mellitus , endocrinology , pharmacology
Aims To evaluate the efficacy and safety of titrated canagliflozin, a sodium glucose co‐transporter 2 inhibitor, in patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled on metformin and sitagliptin. Methods In this randomized, double‐blind study, patients with T2DM (N = 218) on metformin ≥1500 mg/day and sitagliptin 100 mg received canagliflozin 100 mg or placebo. After 6 weeks, the canagliflozin dose was increased from 100 to 300 mg (or from placebo to matching placebo) if all of the following criteria were met: baseline estimated glomerular filtration rate ≥70 ml/min/1.73 m 2 ; fasting self‐monitored blood glucose ≥5.6 mmol/l (≥100 mg/dl); and no volume depletion–related adverse events ( AEs ) within 2 weeks before dose increase. Endpoints included change in glycated haemoglobin ( HbA1c ) at week 26 (primary); proportion of patients achieving HbA1c <7.0%; and changes in fasting plasma glucose ( FPG ), body weight and systolic blood pressure ( SBP ). Safety was assessed using AE reports. Results Overall, 85.4% of patients were titrated to canagliflozin 300 mg or matching placebo (mean ± standard deviation time to titration 6.2 ± 0.8 weeks). At week 26, canagliflozin (pooled 100 and 300 mg) demonstrated superiority in HbA1c reduction versus placebo (−0.91% vs. −0.01%; p < 0.001). Canagliflozin provided significant reductions in FPG , body weight and SBP compared with placebo (p < 0.001). The overall AE incidence was 39.8 and 44.4% for canagliflozin and placebo, respectively. Canagliflozin was associated with an increased incidence of genital mycotic infections. Conclusions Titrated canagliflozin significantly improved HbA1c , FPG , body weight and SBP , and was generally well tolerated over 26 weeks in patients with T2DM as add‐on to metformin and sitagliptin.