Mapping GLP-1 Receptor Agonist Research across the MASLD-MASH-HCC Continuum: A Bibliometric and Translational Analysis

Metabolic dysfunction increasingly shapes the burden of hepatocellular carcinoma (HCC) by linking obesity, type 2 diabetes, insulin resistance, and metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis, fibrosis, cirrhosis, and HCC. GLP-1 receptor agonists (GLP-1RAs) target several upstream metabolic drivers, but the structure and evolution of research connecting GLP-1RAs with the MASLD-MASH-HCC continuum remain unclear. Research output on GLP-1RAs has accelerated in recent years, with a significant increase in publications since 2020. The United States has remained the leading contributor to GLP-1RA research, while China has shown rapid growth in recent years. The evolution of keywords in GLP-1RA research has shifted from glucose lowering, obesity, and insulin resistance to MASLD/MASH, liver fibrosis, HCC risk, drug therapy, and clinical outcomes. These bibliometric patterns have informed the development of a four-domain interpretive framework, which includes systemic metabolic remodeling, intrahepatic lipotoxicity relief, inflammation-fibrosis regulation, and HCC risk and premalignant microenvironment modulation. This framework suggests that GLP-1RAs are best investigated as upstream disease-modifying and risk-reducing agents in metabolically high-risk populations rather than as established direct anti-HCC therapies. Prospective studies with stage-specific liver and cancer outcomes are required to test this translational hypothesis. The available evidence highlights the need for further research on the role of GLP-1RAs in the prevention and treatment of HCC in metabolically high-risk populations. Laboratory researchers and clinicians should consider the potential of GLP-1RAs as a therapeutic strategy for HCC prevention and treatment, and explore the development of new GLP-1RA-based therapies for this indication.