Therapeutic Potential of GLP-1 Receptor Agonists in Metabolic Associated Steatotic Liver Disease

Abstract

Objective: To summarize the current knowledge on the therapeutic potential of GLP-1 receptor agonists in managing metabolic associated steatotic liver disease (MASLD).

Data sources: A literature review was conducted using the search terms GLP-1 agonists, MASLD, NAFLD, nonalcoholic fatty liver disease, treatment, and therapy on PubMed (from January 1, 2019, through February 1, 2025), National Institutes of Health (NIH) (from January 1, 2019, through February 1, 2025), Scopus (from January 1, 2019, through February 1, 2025), and the World Health Organization (WHO) data.

Study selection and data extraction: All relevant clinical trials, review articles, package inserts, and guidelines evaluating clinically relevant evidence regarding the therapeutic potential of GLP-1 agonists in MASLD were considered for inclusion.

Data synthesis: GLP-1 RAs have shown promising results in MASLD treatment. Semaglutide has demonstrated efficacy in reducing liver fat content, inflammation, and fibrosis, with clinical trials indicating improvements in hepatic biomarkers and cardiometabolic risk factors. Similarly, tirzepatide has been associated with substantial weight loss and significant reductions in liver fat and fibrosis markers. Both agents exert their effects through mechanisms involving improved insulin sensitivity, reduced lipid accumulation, and attenuation of hepatic inflammation.

Relevance to patient care and clinical practice: Given the high prevalence of MASLD in patients with obesity and type 2 diabetes, tirzepatide and semaglutide could play a critical role in clinical practice by addressing multiple facets of the disease. Both agents have shown potential in reducing liver fat, improving hepatic biomarkers, and mitigating cardiometabolic risks, which are leading causes of morbidity and mortality in MASLD patients. Incorporating these therapies into MASLD treatment guidelines could significantly enhance patient outcomes by targeting both liver-related and systemic complications of the disease.

Conclusions: GLP1 RAs show great potential in managing MASLD by promoting weight loss, improving glycemic control, and reducing liver inflammation.

Keywords: GLP-1 agonists; MASLD; NAFLD; hepatic steatosis; metabolic syndrome therapy.