GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis

Acta Pharmacol Sin. 2022 May;43(5):1156-1166. doi: 10.1038/s41401-021-00836-9. Epub 2021 Dec 21.

Abstract

Nonalcoholic steatohepatitis (NASH), as a severe form of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. The pathogenesis of NASH is complex and multifactorial, obesity and type 2 diabetes mellitus (T2DM) have been implicated as major risk factors. Glucagon-like peptide-1 receptor (GLP-1R) is one of the most successful drug targets of T2DM and obesity, and its peptidic ligands have been proposed as potential therapeutic agents for NASH. In this article we provide an overview of the pathophysiology and management of NASH, with a special focus on the pharmacological effects and possible mechanisms of GLP-1 mimetics in treating NAFLD/NASH, including dual and triple agonists at GLP-1R, glucose-dependent insulinotropic polypeptide receptor or glucagon receptor.

Keywords: GLP-1 mimetics; GLP-1R; GPCR; NAFLD; NASH; dual agonists; triple agonists.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Obesity / drug therapy

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1