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

Haider Ghazanfar,Faryal Altaf,Iqra Nawaz,Vishwa B Patel,Nismat Javed,Harish Patel,Jaydeep Mahasamudram,Minu C Abraham,Mohamed Farag,Sameer D Kandhi

doi:10.7759/cureus.15141

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.

Highlights

BackgroundOver the past few decades, non-alcoholic fatty liver disease (NAFLD) has come to the forefront as one of the major causes of chronic liver disease all over the world
The prevalence of NAFLD is closely linked to the prevalence of type 2 diabetes mellitus (T2DM), obesity, and genetic polymorphisms that increase susceptibility
NAFLD can be defined as a condition in which the fat content of the liver is more than 5% and where other causes for hepatic steatosis such as excessive alcohol consumption, medications, infections, and other liver pathologies have been ruled out [5,6]

Summary

Introduction

Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has come to the forefront as one of the major causes of chronic liver disease all over the world. One mechanism of action is that GLP-1 agonists improved hepatic and adipose insulin sensitivity, thereby reducing the amount of lipotoxic metabolites and pro-inflammatory mediators in the circulation This reduction in the proinflammatory milieu may explain the beneficial effects of GLP-1 agonists on liver histology [19], especially in the knowledge that persistent inflammation drives fibrosis in NASH. The incidence of nausea, constipation, and vomiting was higher in the 0.4 mg semaglutide group as compared to the placebo group (42% vs 11%, 22% vs 12%, and 15% vs 2%, respectively) In this trial, no significant improvement of the fibrosis stage was seen in the semaglutide group despite NASH resolution and dose-dependent weight loss. Limitations of the study included no implementation of exercise plan and intense diet plan in both the groups, lack of long-term clinical outcomes, racial distribution, and lack of proper documentation regarding alcohol abuse [33]

Conclusions

Disclosures

Nakagawa H

15. Madrazo BL

Findings

17. Armstrong MJ