Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are revolutionizing the management of metabolic and liver diseases, demonstrating effectiveness in controlling blood sugar levels and promoting liver repair. Research suggests that they have protective effects on the liver, demonstrating the potential for fibrosis regression and improved survival rates in patients with advanced liver disease. To synthesize recent advancements in the hepatoprotective effects of GLP-1RAs and their underlying mechanisms, we aimed to provide a comprehensive framework for the development of targeted therapeutics. Our data sources included PubMed and Web of Science, with search terms such as "GLP-1RAs," "liver," "MASLD," "HCC," "inflammatory," "microbiota," "metabolism," and their combinations. We selected reviews, clinical trials, and basic research articles from the past 5 years. GLP-1RAs provide a comprehensive defense against liver damage by exhibiting anti-inflammatory effects and promoting metabolic changes. They significantly modify the immune microenvironment, lower pro-inflammatory cytokines, and prevent the activation of hepatic stellate cells (HSCs), thereby helping to reduce fibrogenesis. This immune-metabolic modulation enhances their effectiveness in treating chronic liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis, and hepatocellular carcinoma (HCC). The combined clinical benefits and mechanistic insights position GLP-1RAs as leaders in addressing glycemic dysregulation and liver diseases, suggesting a transformative approach to the association between metabolic disorders and liver conditions.