{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:45:21Z","timestamp":1792496721569,"version":"4.5.0"},"reference-count":93,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is characterized by poor survival rate and quality of life, while available treatments remain generally limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) originally emerged as drugs for the management of diabetes, but have also been shown to alleviate cardiorenal risk. Furthermore, they have demonstrated a wide range of extraglycemic effects that led to their evaluation as potential therapies for a variety of diseases beyond diabetes, such as obesity, neurogenerative disorders and nonalcoholic fatty liver disease. Given the presence of the GLP-1 receptor in hepatocytes, animal data suggest that GLP-1 RAs could regulate molecular pathways that are deeply involved in the genesis and progression of HCC, including inflammatory responses, tumor cell proliferation and oxidative stress, through direct and indirect effects on liver cells. However, future studies must assess several aspects of the benefit-to-risk ratio of the use of GLP-1 RAs in patients with HCC, including co-administration with approved systemic therapies, the incidence of gastrointestinal side effects in a high-risk population, and weight loss management in individuals with poor nutritional status and high rates of cancer cachexia. In this narrative review, we discuss the potential role of GLP-1 analogs in the treatment of HCC, focusing on the molecular mechanisms that could justify a possible benefit, but also referring to the potential clinical implications and areas for future research.<\/jats:p>","DOI":"10.3390\/cancers14194651","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T21:14:28Z","timestamp":1664140468000},"page":"4651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["How Far beyond Diabetes Can the Benefits of Glucagon-like Peptide-1 Receptor Agonists Go? A Review of the Evidence on Their Effects on Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-8209","authenticated-orcid":false,"given":"Konstantinos","family":"Arvanitakis","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"},{"name":"Basic and Translational Research Unit (BTRU) of Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-1352","authenticated-orcid":false,"given":"Theocharis","family":"Koufakis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-740X","authenticated-orcid":false,"given":"Kalliopi","family":"Kotsa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-3118","authenticated-orcid":false,"given":"Georgios","family":"Germanidis","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"},{"name":"Basic and Translational Research Unit (BTRU) of Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","article-title":"The physiology of glucagon-like peptide 1","volume":"87","author":"Holst","year":"2007","journal-title":"Physiol. 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