The role of glucagon-like peptide-1 receptor agonists in nonalcoholic fatty liver disease

ABSTRACT

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease, associated with obesity, type 2 diabetes mellitus and dyslipidemia, which can lead to liver cirrhosis and hepatocellular carcinoma in some patients. Apart from lifestyle modifications, which are the cornerstone for its management, several drugs are under evaluation, including glucagon-like peptide-1 receptor agonists (GLP-R1RAs). In this review, we summarized major clinical data concerning the effects of GLP-1RAs on NAFLD, trying to highlight existing knowledge and to elucidate areas of uncertainty, thus providing clues to potential clinical implications and research.

Areas covered

Selected clinical studies on GLP-R1As in NAFLD are presented in this narrative review.

Expert opinion

There is evidence that treatment with GLP-R1As in NAFLD has beneficial effects on NAFLD, i.e. improvement in liver function tests and histological improvement in hepatic steatosis and inflammation, but not fibrosis. Further research is required toward the early use of GLP-R1Αs, i.e. in NAFLD patients without fibrosis to evaluate whether they may prevent the progression to fibrosis, or in patients with advanced disease in combination with other medications, which may have additive or even synergistic effects on NAFLD.

KEYWORDS:

• Exenatide
• glucagon-like peptide-1 receptor agonists
• hepatic steatosis
• liraglutide
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• semaglutide
• treatment

Article highlights

• Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease without any approved pharmacological treatment.

• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are glucose-lowering agents that improve liver function tests, as well as hepatic steatosis and inflammation, but not fibrosis, in patients with NAFLD.

• The adverse events of GLP-1RAs are mostly mild to moderate gastrointestinal, including nausea, vomiting, diarrhea, loss of appetite and abdominal discomfort.

Declarations of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.