{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:02:26Z","timestamp":1791838946656,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated unprecedented efficacy in the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, its rapid clinical widespread use has ignited a debate regarding long-term safety, particularly concerning the risk of specific neoplasms and its ability to modulate cardiovascular health, not only as primary prevention but also as a potential agent to mitigate cardiotoxicity. Objectives: This narrative review aims to analyze the most recent evidence from clinical trials and post-marketing surveillance to evaluate the correlation between semaglutide use and the incidence of cancer, as well as the drug\u2019s efficacy in reducing cardiotoxicity induced by anticancer therapies. Results and Discussion: While preclinical rodent models suggested a link to medullary thyroid carcinoma, human epidemiological data remain reassuring, though caution is advised in patients with genetic predisposition. Regarding pancreatic cancer, current meta-analyses do not confirm a significant increase in risk, suggesting that metabolic benefits outweigh potential concerns. Conclusions: Semaglutide is confirmed as a therapeutic tool with a highly favorable benefit\u2013risk profile. While oncological monitoring must continue, the drug\u2019s cardioprotective and anti-inflammatory properties open new frontiers not only in metabolic management but also in safeguarding cardiovascular integrity in complex clinical scenarios.<\/jats:p>","DOI":"10.3390\/ph19020297","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:10:52Z","timestamp":1770743452000},"page":"297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Impact of Semaglutide Beyond Glycemic Control: A Critical Analysis of Oncogenic Potential and Mitigation of Cardiotoxicity"],"prefix":"10.3390","volume":"19","author":[{"given":"Adriana","family":"Correra","sequence":"first","affiliation":[{"name":"Cardiology Department, Ospedali Riuniti University Hospital, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7060-6938","authenticated-orcid":false,"given":"Alfredo","family":"Mauriello","sequence":"additional","affiliation":[{"name":"S.C. Cardiology, Institute National Cancer, IRCCS, Fondazione \u201cG. Pascale\u201d, Via M. Semmola 52, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-0188","authenticated-orcid":false,"given":"Valeria","family":"Cetoretta","sequence":"additional","affiliation":[{"name":"Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital \u201cOspedali Riuniti\u201d, Via Conca 71, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Maratea","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Disease, ASL Napoli 1 Centro, Via Comunale del Principe, 13\/a, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Riegler","sequence":"additional","affiliation":[{"name":"Cardiology and Intensive Care Unit, Department of Cardiology, \u201cUmberto I\u201d Hospital, Via Alfonso De Nicola 1, 84014 Nocera Inferiore, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Di Sarno","sequence":"additional","affiliation":[{"name":"UOSD Neurophysiopathology, AORN \u201cSantobono Pausillipon\u201d, Via Mario Fiore, 6, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-9397","authenticated-orcid":false,"given":"Francesco","family":"Giallauria","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-1312","authenticated-orcid":false,"given":"Federico","family":"Guerra","sequence":"additional","affiliation":[{"name":"Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital \u201cOspedali Riuniti\u201d, Via Conca 71, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-0360","authenticated-orcid":false,"given":"Vincenzo","family":"Russo","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Medical and Translational Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, \u201cV. Monaldi\u201d Hospital, Via Leonardo Bianchi snc, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9145","authenticated-orcid":false,"given":"Antonello","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Cardiology and Intensive Care Unit, Department of Cardiology, \u201cUmberto I\u201d Hospital, Via Alfonso De Nicola 1, 84014 Nocera Inferiore, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2337\/dc14-2441","article-title":"Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1021\/acs.jmedchem.5b00726","article-title":"Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide","volume":"58","author":"Lau","year":"2015","journal-title":"J. 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