title: Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes.
abstract: OBJECTIVE
  To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist].
  
  
  METHODS
  CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18.
  
  
  RESULTS
  Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues.
  
  
  CONCLUSIONS
  In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.
authors.affiliation: The Royal North Shore Hospital and University of Sydney, Sydney, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Fulcher
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
authors.affiliation: The George Institute for Global Health, The Royal Prince Alfred Hospital, and University of Sydney, Sydney, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Endocrinology Section, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Woo
authors.affiliation: Washington State University, Spokane, WA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wysham
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Capuano
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Desai
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Shaw
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Vercruysse
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Meininger
authors.affiliation: The George Institute for Global Health, The Royal Prince Alfred Hospital, and University of Sydney, Sydney, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Neal
mesh_terms: D000368:Aged; D032701:Biomimetics; D001794:Blood Pressure / Q000187:drug effects; D000068896:Canagliflozin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D054795:Incretins / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D014570:Urologic Diseases / Q000139:chemically induced / Q000382:microbiology; D015431:Weight Loss / Q000187:drug effects; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000068896:Canagliflozin; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human
keywords: canagliflozin; type 2 diabetes