title: Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study.
abstract: OBJECTIVE
  To assess the efficacy/safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with glimepiride over 104 weeks in patients with type 2 diabetes inadequately controlled with metformin.
  
  
  METHODS
  In this randomized, double-blind study, patients (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride (titrated up to 6 or 8 mg/day) during a 52-week core period followed by a 52-week extension.
  
  
  RESULTS
  At week 104, reductions from baseline in A1C were -0.65%, -0.74%, and -0.55% (-7.1, -8.1, and -6.0 mmol/mol) with canagliflozin 100 and 300 mg and glimepiride, respectively. Durability analyses showed sustained A1C lowering with both canagliflozin doses versus glimepiride. Reductions in body weight (-4.1%, -4.2%, and 0.9%, respectively) and systolic blood pressure (-2.0, -3.1, and 1.7 mmHg, respectively) were seen with canagliflozin 100 and 300 mg compared with glimepiride at week 104. The overall adverse event (AE) incidence was 73.3%, 77.9%, and 78.4% with canagliflozin 100 and 300 mg and glimepiride; the incidence of AE-related discontinuations was low across groups (6.2%, 9.5%, and 7.3%, respectively). Incidences of genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs were higher with canagliflozin than glimepiride; these were generally mild to moderate in intensity and led to few discontinuations. Fewer patients had hypoglycemia episodes with canagliflozin 100 and 300 mg than glimepiride (6.8%, 8.2%, and 40.9%). Mild decreases in estimated glomerular filtration rate occurred initially with canagliflozin; these attenuated over 104 weeks.
  
  
  CONCLUSIONS
  Canagliflozin provided durable glycemic improvements compared with glimepiride and was generally well tolerated in patients with type 2 diabetes receiving background treatment with metformin over 104 weeks.
authors.affiliation: Keenan Research Centre, The Li Ka Shing Knowledge Institute, St. Michael's Hospital; Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada leiterl@smh.ca.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Department of Endocrinology & Metabolism, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: University of Rosario Medical School, Rosario, Argentina Litoral University Medical School, Santa Fe, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Arias
authors.affiliation: Lipid Clinic, Oslo University Hospital, Oslo, Norway.
authors.forename: Gisle
authors.initials: G
authors.lastname: Langslet
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ.
authors.forename: John
authors.initials: J
authors.lastname: Xie
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ.
authors.forename: Dainius A
authors.initials: DA
authors.lastname: Balis
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ.
authors.forename: Dawn
authors.initials: D
authors.lastname: Millington
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Vercruysse
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ.
authors.forename: William
authors.initials: W
authors.lastname: Canovatchel
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ.
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
mesh_terms: D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D013876:Thiophenes; D000068896:Canagliflozin; C057619:glimepiride; D008687:Metformin