title: Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease in Western societies. Despite its significance, there are no well-proven pharmacological treatments. Two novel classes of potential pharmacotherapies are the glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4I), collectively known as incretin-based therapies. These have several metabolic and anti-inflammatory actions that may be of benefit in NAFLD. The aim of this meta-analysis was to evaluate their efficacy via a structured retrieval and pooled analysis of relevant studies.
  
  
  METHODS
  Studies were sourced from electronic databases and meeting abstracts. Main inclusion criteria were original studies investigating treatment of adults with NAFLD using GLP-1 RA/DPP-4I. Key outcomes were a change in serum alanine transaminase (ALT), as a marker of liver inflammation, and improvement in disease status measured by imaging or histology.
  
  
  RESULTS
  Initial searching retrieved 1357 peer-reviewed articles and abstracts. Four studies met all inclusion and exclusion criteria. There were a total of 136 participants with NAFLD and concomitant type 2 diabetes mellitus (T2DM). Meta-analysis (random-effects model) revealed a significant decrease in serum ALT following treatment (mean reduction 14.1 IU/L, 95% confidence intervals [CI] 8.3-19.8, P < 0.0001). In two studies with imaging and tissue data, treatment was found to significantly reduce steatosis, inflammation, and fibrosis.
  
  
  CONCLUSIONS
  The significant decrease in a key biochemical marker of hepatic inflammation following treatment with incretin-based therapies, as well as improvements in imaging and histology, suggests these agents may be effective options for managing NAFLD with comorbid T2DM.
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Carbone
authors.affiliation: Department of Gastroenterology and Hepatology, Austin Health, Melbourne, Victoria, Australia.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Angus
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Neville D
authors.initials: ND
authors.lastname: Yeomans
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000893:Anti-Inflammatory Agents; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D016206:Databases, Bibliographic; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D054795:Incretins / Q000494:pharmacology / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D000410:Alanine Transaminase; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: DPP-4I; GLP-1 RA; NAFLD; NASH; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; incretin system; treatment