title: Impact of Age and Estimated Glomerular Filtration Rate on the Glycemic Efficacy and Safety of Canagliflozin: A Pooled Analysis of Clinical Studies.
abstract: OBJECTIVE
  Reduced efficacy has been reported in the elderly; it may be a consequence of an age-dependent decline in estimated glomerular filtration rate (eGFR) rather than ageing per se. We sought to determine the impact of these 2 parameters, as well as sex and baseline body mass index (BMI), on the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in people with type 2 diabetes.
  
  
  METHODS
  Data were pooled from 6 randomized, double-blind, placebo-controlled studies (18 or 26 weeks; N=4053). Changes in glycated hemoglobin (A1C) and systolic blood pressure (BP) from baseline with canagliflozin 100 mg and 300 mg and placebo were evaluated in subgroups by sex, baseline BMI, baseline age and baseline eGFR. Safety was assessed by reports of adverse events.
  
  
  RESULTS
  Placebo-subtracted reductions in A1C with canagliflozin 100 mg and 300 mg were similar in men and women. A1C reductions with canagliflozin were seen across BMI subgroups and in participants aged <65 years and ≥65 years. Significantly greater placebo-subtracted reductions in A1C were seen with both canagliflozin doses in participants with higher baseline eGFR (≥90 mL/min/1.73 m(2)). Reductions in systolic BP were seen with canagliflozin across subgroups of sex, BMI, age and eGFR. A1C reductions with canagliflozin were similar for participants aged <65 or ≥65 years who had baseline eGFR ≥60 mL/min/1.73 m(2) and were smaller in older than in younger participants with baseline eGFR 45 to <60 mL/min/1.73 m(2). The overall incidence of adverse events was similar across treatment groups regardless of sex, baseline BMI, baseline age or baseline eGFR.
  
  
  CONCLUSIONS
  Canagliflozin improved glycemic control, reduced BP and was generally well tolerated in people with type 2 diabetes across a range of ages, BMIs and renal functions.
authors.affiliation: Keenan Research Centre, Li KaShing Knowledge Institute of St. Michael's Hospital, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Canada. Electronic address: richard.gilbert@utoronto.ca.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
authors.affiliation: University of Maryland Medical Center, Baltimore, Maryland, United States of America.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fioretto
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey, United States of America.
authors.forename: Gordon
authors.initials: G
authors.lastname: Law
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey, United States of America.
authors.forename: Mehul
authors.initials: M
authors.lastname: Desai
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey, United States of America.
authors.forename: Irina
authors.initials: I
authors.lastname: Kline
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey, United States of America.
authors.forename: Wayne
authors.initials: W
authors.lastname: Shaw
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
mesh_terms: D000367:Age Factors; D000368:Aged; D001786:Blood Glucose; D001794:Blood Pressure; D015992:Body Mass Index; D000068896:Canagliflozin / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: clinical study; diabète de type 2; glycemic control; régulation de la glycémie; traitement; treatment; type 2 diabetes; étude clinique