title: Effect of canagliflozin on liver function tests in patients with type 2 diabetes.
abstract: OBJECTIVE
  To report changes in liver function tests observed with canagliflozin, a sodium glucose co-transporter 2 inhibitor, across phase 3 studies in patients with type 2 diabetes, and to examine the relationship between changes in liver function tests and the weight loss and glycaemic improvements observed with canagliflozin.
  
  
  METHODS
  Data were pooled from four 26-week, placebo-controlled studies of canagliflozin 100 and 300mg (n=2313) and two 52-week, active-controlled studies of canagliflozin 300mg versus sitagliptin 100mg (n=1488). Analysis of covariance was performed to determine the contribution of changes in body weight and HbA1c to the changes in liver function tests.
  
  
  RESULTS
  Reductions in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase, and increases in bilirubin were seen with canagliflozin 100 and 300mg versus placebo (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase [both doses]; P<0.001 for alkaline phosphatase and P=0.015 for bilirubin [canagliflozin 300mg only]) at week 26 and with canagliflozin 300mg versus sitagliptin 100mg (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and bilirubin, and P<0.01 for alkaline phosphatase) at week 52. Few patients met predefined limits of change criteria for liver function tests, and none met Hy's law criteria. In both populations, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase reductions were fully explained by HbA1c and body weight reductions.
  
  
  CONCLUSIONS
  Canagliflozin provided improvements in liver function tests versus either placebo or sitagliptin treatments that were fully explained by the combined effects of HbA1c and body weight reductions with canagliflozin.
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Division of Endocrinology and Metabolism, University of Toronto, 61 Queen Street East, #6121, Toronto, ON, Canada M5C 2T2. Electronic address: leiterl@smh.ca.
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Profil Mainz, Rheinstr. 4c 55116, Mainz, Germany. Electronic address: Thomas.Forst@Profil.com.
authors.forename: T
authors.initials: T
authors.lastname: Forst
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA. Electronic address: dpolido1@its.jnj.com.
authors.forename: D
authors.initials: D
authors.lastname: Polidori
authors.affiliation: Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Electronic address: DBalis@its.jnj.com.
authors.forename: D A
authors.initials: DA
authors.lastname: Balis
authors.affiliation: Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Electronic address: JXie2@its.jnj.com.
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.affiliation: Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869, USA. Electronic address: ssha@its.jnj.com.
authors.forename: S
authors.initials: S
authors.lastname: Sha
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D000068896:Canagliflozin / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents
keywords: Body weight reduction; Canagliflozin; Glycaemic control; Liver function tests; Sodium glucose co-transporter 2 inhibitor; Type 2 diabetes mellitus