title: Effects of lixisenatide on elevated liver transaminases: systematic review with individual patient data meta-analysis of randomised controlled trials on patients with type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the effects of the glucagon-like peptide-1 receptor agonist lixisenatide on elevated liver blood tests in patients with type 2 diabetes.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Electronic and manual searches were combined.
  
  
  METHODS
  Randomised controlled trials (RCTs) on lixisenatide versus placebo or active comparators for type 2 diabetes were included.
  
  
  METHODS
  Individual patient data were retrieved to calculate outcomes for patients with elevated liver blood tests.
  
  
  METHODS
  Normalisation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
  
  
  RESULTS
  The results of included trials were combined in meta-analyses. Sequential, subgroup and regression analyses were performed to evaluate heterogeneity and bias.
  
  
  RESULTS
  We included 12 RCTs on lixisenatide versus placebo and 3 RCTs with the active comparators liraglutide, exenatide or sitagliptin. The mean treatment duration was 29 weeks. Lixisenatide increased the proportion of patients with normalisation of ALT (risk difference: 0.07; 95% CI 0.01 to 0.14; number needed to treat: 14 patients, p=0.042). The effect was not confirmed in sequential analysis. No effects of lixisenatide were identified on AST, alkaline phosphatase or bilirubin. No evidence of bias was identified. Mixed effect multilevel meta-regression analyses suggest that the benefit of lixisenatide on ALT was limited to patients who were overweight or obese.
  
  
  CONCLUSIONS
  This review suggests that lixisenatide increases the proportion of obese or overweight patients with type 2 diabetes who achieve normalisation of ALT. Additional research is needed to determine if the findings translate to clinical outcome measures.
  
  
  BACKGROUND
  PROSPERO; CRD42013005779.
authors.affiliation: Department of Medicine, Diabetes Research Centre, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Lise L
authors.initials: LL
authors.lastname: Gluud
authors.affiliation: Department of Medicine, Diabetes Research Centre, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Department of Medicine, Diabetes Research Centre, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease / Q000201:enzymology / Q000517:prevention & control; D009765:Obesity / Q000517:prevention & control; D010455:Peptides / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D015415:Biomarkers; D007004:Hypoglycemic Agents; D010455:Peptides; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor