Therapeutic Mechanisms and Clinical Effects of Glucagon-like Peptide 1 Receptor Agonists in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) can lead to liver fibrosis and cirrhosis. Recently, glucagon-like peptide 1 receptor agonists (GLP-1RAs), a class of drugs used to treat type 2 diabetes and obesity, have shown therapeutic effects against NAFLD. In addition to reducing blood glucose levels and body weight, GLP-1RAs are effective in improving the clinical, biochemical, and histological markers of hepatic steatosis, inflammation, and fibrosis in patients with NAFLD. Additionally, GLP-1RAs have a good safety profile with minor side effects, such as nausea and vomiting. Overall, GLP-1RAs show promise as a potential treatment for NAFLD, and further studies are required to determine their long-term safety and efficacy.

Keywords: diabetes; liraglutide; nonalcoholic steatohepatitis; semaglutide; tirzepatide.

Figure 1

Therapeutic mechanisms of GLP-1RA treatment in patients with NAFLD. Abbreviations: GLP-1RA, Glucagon-like peptide-1 receptor agonist; NAFLD, nonalcoholic fatty liver disease; TNF, tumor necrosis factor, ER, endoplasmic reticulum.

Figure 2

Mechanism of NASH development and treatment target of GLP-1RAs. Abbreviations: NASH, nonalcoholic steatohepatitis; GLP-1RA, Glucagon-like peptide-1 receptor agonist; NEFA, nonesterified fatty acids; FGF, fibroblast growth factor; VLDL, very low density lipoprotein; FFA, free fatty acid; LPS, lipopolysaccharide; GIP, glucose dependent insulinotropic peptide; ROS, reactive oxygen species; ER, endoplasmic reticulum; LD, lipid droplet; DNL, de novo lipogenesis.