The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists

📖 Top 20% JournalFeb 28, 2025Expert opinion on investigational drugs

Multiple effects of glucagon-like peptide-1 receptor drugs in patients with fatty liver disease linked to metabolism

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

GLP-1 receptor agonists are associated with clinically relevant hepatic improvements, including MASH resolution.

Phase I - III trials indicate that GLP-1 receptor agonists may lead to liver fat reduction and prevent worsening fibrosis.
Improvements in glycemic control, weight, and cardiovascular outcomes are observed in patients with type 2 diabetes and obesity.
The use of GLP-1 receptor agonists is linked to potential benefits in comorbid conditions such as obstructive sleep apnea and chronic kidney disease.
GLP-1 receptor agonists could be a valuable treatment option for gastroenterologists addressing MASLD/MASH and related cardiometabolic disorders.

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INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) or glucagon receptor agonists have emerged as promising agents to treat metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). Although the beneficial effects of GLP-1RAs on glycemic control and weight are well-established, clinicians may be unfamiliar with other potential benefits of this class.

AREAS COVERED: We examined the pleiotropic effects of GLP-1RAs and how they relate to gastroenterologists for MASLD/MASH treatment. Our narrative review of English articles included four GLP-1RAs (subcutaneous semaglutide, liraglutide, dulaglutide, and efpeglenatide), a dual GLP-1/GIP agonist (tirzepatide), a dual GLP-1/glucagon receptor agonist (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes and landscape.

EXPERT OPINION: In Phase I - III trials, GLP-1RAs are associated with clinically relevant hepatic improvements including MASH resolution, liver fat reduction, and preventing worsening fibrosis. Effects on cardiometabolic parameters align with type 2 diabetes/obesity Phase III data, comprising substantial improvements in glycemic, weight, and cardiovascular outcomes. Promising data also suggest benefits in common comorbidities, including obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.GLP-1RAs represent a valuable pharmacotherapeutic option for gastroenterologists managing individuals with MASLD/MASH and cardiometabolic comorbid conditions.

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