title: Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies.
abstract: BACKGROUND
  Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in patients with T2DM <65 and ≥65 years of age.
  
  
  METHODS
  Pooled data from 4 randomised, placebo-controlled, 26-week, Phase 3 studies (N = 2,313) evaluating canagliflozin 100 and 300 mg were analysed by age: <65 years (n = 1,868; mean age, 52.8 years) or ≥65 years (n = 445; mean age, 69.3 years). Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure (BP), and percent change from baseline in body weight. Assessment of safety/tolerability included adverse event (AE) reports, incidence of documented hypoglycaemia, and percent change from baseline in fasting plasma lipids.
  
  
  RESULTS
  Canagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients <65 and ≥65 years of age. Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients <65 and ≥65 years of age. Incidence of overall AEs was similar across all treatment groups in patients <65 and ≥65 years of age. Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients <65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age. As in patients <65 years of age, incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age. Incidences of urinary tract infections (UTIs), renal-related AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients <65 years of age. Changes in lipid parameters with canagliflozin were similar in both age subsets.
  
  
  CONCLUSIONS
  Canagliflozin improved glycaemic control, body weight, and systolic BP, and was generally well tolerated in older patients with T2DM.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01081834; NCT01106677; NCT01106625; NCT01106690.
authors.affiliation: Luton & Dunstable University Hospital; Bedfordshire and Hertfordshire Postgraduate Medical School, University of Bedfordshire, Putteridge Bury Campus, Hitchin Road, Luton LU2 8LE, UK. Alan.Sinclair@beds.ac.uk.
authors.forename: Alan
authors.initials: A
authors.lastname: Sinclair
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.forename: Stewart
authors.initials: S
authors.lastname: Harris
authors.forename: Ujjwala
authors.initials: U
authors.lastname: Vijapurkar
authors.forename: Cristiana
authors.initials: C
authors.lastname: Mayer
authors.forename: Albert
authors.initials: A
authors.lastname: Fung
authors.forename: Wayne
authors.initials: W
authors.lastname: Shaw
authors.forename: Keith
authors.initials: K
authors.lastname: Usiskin
authors.forename: Mehul
authors.initials: M
authors.lastname: Desai
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068896:Canagliflozin; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D005960:Glucosides; D013876:Thiophenes; D000068896:Canagliflozin
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