{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:41:53Z","timestamp":1786477313828,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>While glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) show promise for hepatoprotection in type 2 diabetes mellitus (T2DM), the magnitude of hepatocellular carcinoma (HCC) risk reduction and optimal patient selection remain unclear. This is particularly relevant given that metabolic dysfunction\u2010associated steatotic liver disease (MASLD) affects 70% of patients with T2DM and represents a major HCC risk factor. We conducted a comprehensive meta\u2010analysis to quantify GLP\u20101RA efficacy in HCC prevention and inform clinical implementation strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase, and Web of Science through June 2025 for cohort studies comparing HCC incidence between GLP\u20101RA users and nonusers with T2DM. Random\u2010effects meta\u2010analysis, network meta\u2010analysis, and meta\u2010regression were performed. Heterogeneity was explored through stratified analyses and quantitative bias assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine studies encompassing 2,283,835 total patients (analyzed cohorts: 1,012,482) were included. GLP\u20101RA use was associated with a 42% reduced HCC risk (pooled HR 0.60, 95% CI: 0.41\u20130.88;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200986.2%). Effect magnitude varied significantly by comparator: versus insulin (HR 0.29, 95% CI: 0.13\u20130.67), versus oral agents (HR 0.81, 95% CI: 0.63\u20131.05), versus no treatment (HR 0.77, 95% CI: 0.52\u20131.14). Meta\u2010regression identified insulin as comparator as the primary driver of heterogeneity, explaining 55% of the between\u2010study variance. Benefits were greatest in patients without cirrhosis (HR 0.41, 95% CI: 0.29\u20130.58). Network meta\u2010analysis ranked GLP\u20101RAs highest for HCC prevention (SUCRA 0.89), with insulin ranking lowest (0.08). The number needed to treat ranged from 24 to 476.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GLP\u20101RAs substantially reduce HCC risk in T2DM, with benefits partly attributable to avoiding insulin's potential hepatotoxicity. These findings support the preferential use of GLP\u20101RAs over insulin in patients at HCC risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71434","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:40:24Z","timestamp":1765604424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Glucagon\u2010Like Peptide\u20101 Receptor Agonists and Hepatocellular Carcinoma Prevention: A Meta\u2010Analysis and Clinical Decision Framework"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0402-4176","authenticated-orcid":false,"given":"Andrea","family":"Dalbeni","sequence":"first","affiliation":[{"name":"Unit of General Medicine C, Medicine Department University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"},{"name":"Liver Unit, Medicine Departmen University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6012-1524","authenticated-orcid":false,"given":"Marco","family":"Vicardi","sequence":"additional","affiliation":[{"name":"Unit of General Medicine C, Medicine Department University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"},{"name":"Liver Unit, Medicine Departmen University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0465-8486","authenticated-orcid":false,"given":"Leonardo Antonio","family":"Natola","sequence":"additional","affiliation":[{"name":"Unit of General Medicine C, Medicine Department University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"},{"name":"Liver Unit, Medicine Departmen University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Cattazzo","sequence":"additional","affiliation":[{"name":"Unit of General Medicine C, Medicine Department University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"},{"name":"Liver Unit, Medicine Departmen University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Auriemma","sequence":"additional","affiliation":[{"name":"Section of Innovation Biomedicine\u2010Oncology Area, Department of Engineering for Innovation Medicine (DIMI) University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Lombardi","sequence":"additional","affiliation":[{"name":"SC Medicina Indirizzo Metabolico Fondazione IRCCS Ca' Grande Ospedale Maggiore Policlinico di Milano  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Cinque","sequence":"additional","affiliation":[{"name":"SC Medicina Indirizzo Metabolico Fondazione IRCCS Ca' Grande Ospedale Maggiore Policlinico di Milano  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Dalle Carbonare","sequence":"additional","affiliation":[{"name":"Unit of General Medicine C, Medicine Department University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine University and Azienda Ospedaliera Universitaria Integrata of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sacerdoti","sequence":"additional","affiliation":[{"name":"Liver Unit, Medicine Departmen University of Verona and University and Hospital Trust (AOUI) of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00381-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2024.0109"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.11.010"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2019.11.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3122\/jabfm.2023.230455R1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021703"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.08.038"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.07.033"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.70000"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902\u2010024\u201001775\u20102"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102024\u2010334591"},{"key":"e_1_2_10_13_1","unstructured":"G. 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