Regenerative and Hepatotropic Properties of GLP-1 and GLP-2: Mechanistic Insights and Implications for Post-Hepatectomy Liver Regeneration: A Narrative Review

Background: Liver regeneration after hepatectomy is critical for recovery, yet post-hepatectomy liver failure (PHLF) remains a significant challenge. While GLP-1 RAs have shown metabolic and hepatic benefits in conditions like metabolic dysfunction–associated steatotic liver disease, and GLP-2 is known for intestinotrophic properties, their specific roles in PHLF are not well-defined. This narrative review aims to examine the roles of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Glucagon-like peptide-2 (GLP-2) in liver regeneration following partial hepatectomy. Methods: A narrative review was conducted, involving a structured appraisal of preclinical, translational, and clinical studies. Relevant literature was identified through comprehensive searches of PubMed and EMBASE databases, limited to English-language publications available up to 1 May 2025. Results: GLP-1 RAs demonstrate therapeutic potential in chronic metabolic liver diseases, but their role in acute hepatic regeneration appears unfavorable, with animal models showing attenuated regenerative responses and impaired liver mass restoration. Conversely, preclinical studies indicate that GLP-2 administration enhances liver regeneration, and human data reveal increased circulating GLP-2 levels post-resection, particularly in PHLF patients, showing dynamics inverse to GLP-1. Conclusions: GLP-1 RAs appear to inhibit acute hepatic regeneration following hepatectomy, while GLP-2 exhibits pro-regenerative activity in preclinical models and favorable dynamics in humans post-resection.