Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Non-Alcoholic Steatohepatitis: A Clinical Review Article

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the lethal causes of chronic liver disease globally. NAFLD can ultimately progress to non-alcoholic steatohepatitis (NASH) given persistent cellular insult. The crux of the problem lies in fat accumulation in the liver, such as increased fatty acid substrates owing to consumption of a high-fat diet, altered gut physiology, and excess adipose tissue. Being the hepatic manifestation of metabolic syndrome, insulin resistance is also among one of the many stimuli. Therefore, drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA) can play a significant role in reducing inflammation, in addition to weight loss and dietary habits. In this review article, we have reviewed the role of exenatide, liraglutide, and semaglutide in the management of NASH. Two of the agents, exenatide and semaglutide, have a predominant role in reducing alanine aminotransferase (ALT) levels, therefore reducing inflammation and promoting weight loss. However, these agents have a lesser impact on the degree of fibrosis. Liraglutide, on the other hand, has been shown to significantly decrease the degree of fibrosis and has been found helpful in reversing mild degrees of steatosis. Therefore, these agents warrant attention to the new perspective that has been presented so that future guidelines may incorporate and streamline individualized therapy.

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

“…In a randomized controlled clinical trial, exenatide clearly reduced liver fat content in patients with drug-naïve T2DM and NAFLD, and led to greater reductions of body weight, visceral fat, and liver enzymes than insulin glargine ( Liu L. et al, 2020 ). Several studies have shown that exenatide has a predominant role in reducing ALT levels, thereby promoting weight loss, inhibiting inflammation to some extent, and preventing deterioration of steatosis ( Ghazanfar et al, 2021 ). Exenatide may be incorporated into streamlined individualized therapy for NAFLD.…”

The Gut Microbiome and Ferroptosis in MAFLD

“…GLP-1 has a very short half-life in vivo, and is degraded by dipeptidyl peptidase-4 (DPP-4), so it cannot be used for disease treatment. 184 GLP-1 RA belongs is an incretin drug with pleiotropic effects such as lowering blood glucose and blood lipids and reducing body weight. 185 Recent studies have found that GLP-1 RA improved IR in NAFLD, reduced liver steatosis, and improved liver fibrosis.…”

Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs

“…Furthermore, exenatide demonstrated an ability to decrease the lipid content and inflammation in the liver of APOE*3-Leiden.CETP mice by inhibiting the expression of liver chemokines and the gathering of oxLDL in macrophages [ 152 ]. GLP-1 RAs activity on both hepatic and adipose tissue, which is linked with suppressed expression of pro-inflammatory mediators, such as cytokines (e.g., IL-6 and TNF-a) and chemokines (e.g., monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin), is fundamental in regulating fibrosis in NASH [ 153 , 154 ]. Moreover, this downregulation, along with an inhibition of macrophage infiltration, plays an important role in enhancing insulin sensitivity.…”