title: Effect of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on bacteriuria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week, phase 2 study.
abstract: OBJECTIVE
  To examine the effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor that lowers blood glucose by increasing urinary glucose excretion (UGE), on asymptomatic bacteriuria and urinary tract infections (UTIs).
  
  
  METHODS
  In a randomized, double-blind, placebo-controlled, multicenter, dose-ranging phase 2 study, subjects with type 2 diabetes with inadequate glycemic control while receiving metformin were enrolled and randomized to one of seven arms - placebo; canagliflozin doses 50 mg, 100 mg, 200 mg, 300 mg daily, or 300 mg twice daily; and sitagliptin 100 mg daily - for 12 weeks.
  
  
  BACKGROUND
  This study is registered under Clinicaltrials.gov identification number NCT00642278.
  
  
  RESULTS
  Canagliflozin increased renal glucose excretion by 35.4-61.6 mg/mg creatinine in the five dose groups. In the placebo group renal glucose excretion was increased by 1.9 mg/mg creatinine, and in the sitagliptin group it decreased by 1.9 mg/mg creatinine. Asymptomatic bacteriuria (ASB) were present in 6.4% of canagliflozin and 6.5% of placebo/sitagliptin (control) subjects at randomization and, at 12 weeks, in 7.7% and 6.3% of subjects, respectively (odds ratio [OR] 1.23; 95% confidence interval [CI], 0.45-3.89). For subjects with initially negative urine cultures at baseline, 3 out of 82 (3.7%) who received controls and 10 out of 207 (4.8%) who received canagliflozin developed bacteriuria (p = 0.76) at week 12. There were 21 adverse event (AE) reports of UTI; 16 (5.0%) in canagliflozin subjects and 5 (3.8%) in control subjects (OR 1.31; 95% CI, 0.45-4.68).
  
  
  CONCLUSIONS
  In this trial, when compared with control subjects, canagliflozin increased UGE but was not associated with increased bacteriuria or AE reports of UTI. However, further studies enrolling larger numbers of subjects with longer term exposure to canagliflozin will be necessary to more fully understand the impact of this agent on the risk of developing UTI.
authors.affiliation: University of Manitoba, Winnipeg, Canada. LNicolle@exchange.hsc.mb.ca
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Nicolle
authors.forename: G
authors.initials: G
authors.lastname: Capuano
authors.forename: K
authors.initials: K
authors.lastname: Ways
authors.forename: K
authors.initials: K
authors.lastname: Usiskin
mesh_terms: D001437:Bacteriuria / Q000453:epidemiology*; D001786:Blood Glucose / Q000032:analysis; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D006029:Glycosuria / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000453:epidemiology*
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D011719:Pyrazines; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D014230:Triazoles; D000068896:Canagliflozin; D008687:Metformin; D000068900:Sitagliptin Phosphate