title: Canagliflozin in the treatment of type 2 diabetes: an evidence-based review of its place in therapy.
abstract: BACKGROUND
  Deciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium-glucose co-transporter 2 (SGLT2) inhibitors.
  
  
  OBJECTIVE
  The aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes.
  
  
  METHODS
  Compared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0.6%-0.8%, respectively. Canagliflozin appears to be slightly more effective than dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing HbA1c. It also has a favorable effect on body weight and blood pressure, both versus placebo and most active comparators. However, treatment with canagliflozin is associated with increased incidence of genital tract infections and osmotic diuresis-related adverse events. Based on short-term data, canagliflozin is not associated with increased risk for all-cause mortality and cardiovascular outcomes. Economic evaluation studies from various countries indicate that canagliflozin is a cost-effective option in dual- or triple-agent regimens.
  
  
  CONCLUSIONS
  As monotherapy, canagliflozin could be used in patients for whom metformin is contraindicated or not tolerated. For patients on background treatment with metformin, canagliflozin appears to be superior to sulfonylureas with respect to body weight, blood pressure and risk for hypoglycemia, and to DPP-4 inhibitors in terms of lowering HbA1c, body weight, and blood pressure. Canagliflozin also seems to be cost-effective compared with sulfonylureas and DPP-4 inhibitors as add-on to metformin monotherapy, and compared with DPP-4 inhibitors as add-on to metformin and sulfonylurea.
  
  
  CONCLUSIONS
  Current evidence on intermediate efficacy outcomes, short-term safety and cost-effectiveness support the use of canagliflozin in patients on background treatment with metformin. Robust long-term data regarding the effect of canagliflozin on cardiovascular endpoints will be available upon completion of the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial.
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Karagiannis
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Bekiari
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; Harris Manchester College, University of Oxford, Oxford, United Kingdom.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Tsapas
keywords: canagliflozin; cardiovascular outcomes; cost-effectiveness; efficacy; evidence-based review; safety; tolerability; type 2 diabetes mellitus