Potential of incretin-based therapies for non-alcoholic fatty liver disease

J Diabetes Complications. 2013 Jul-Aug;27(4):401-6. doi: 10.1016/j.jdiacomp.2012.12.005. Epub 2013 Jan 24.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic, paralleling the increased prevalence of obesity and diabetes, which are risk factors. In this review, we present the current pre-clinical evidence showing that GLP-1 analogues and DPP4 inhibitors can improve hepatic steatosis. Although some of the effects could be due to overall improvement in metabolic parameters, there are data to support improvements independent of weight loss, as well as direct effects on the hepatocyte in vitro. Multiple hepatocyte signal transduction pathways appear to be activated by GLP-1 and its analogues, with both AMP-activated protein kinase and Akt proposed to be key players in improving hepatic steatosis. However, it is controversial as to whether the pancreatic-type GLP-1 receptor is present or responsible for conferring the GLP-1 signal in the hepatocyte. In total, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies for treatment of NAFLD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Fatty Liver / drug therapy*
  • Fatty Liver / epidemiology
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / therapeutic use*
  • Non-alcoholic Fatty Liver Disease

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Incretins
  • Glucagon-Like Peptide 1