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Beyond their metabolic benefits, emerging evidence suggests that GLP-1 RAs may exert anticancer effects by modulating critical biological pathways involved in tumorigenesis, including insulin signaling, inflammation, and cellular proliferation. Current evidence derived from observational and secondary analyses suggests potential protective effects of GLP-1 RAs against several cancers\u2014including prostate, breast, pancreatic, gynecological, glioma, and oral squamous cell cancer through both weight-dependent and independent mechanisms, but the absence of large-scale randomized controlled trials (RCTs) with cancer-specific endpoints remains a critical limitation. Moreover, safety concerns remain a major challenge. Although rodent studies raised concerns regarding medullary thyroid carcinoma, human data have not substantiated a significant risk. Similarly, initial signals of pancreatitis and pancreatic cancer risk have been largely attenuated by subsequent rigorous analyses. Common side effects, such as gastrointestinal discomfort, are usually manageable and transient, but rare adverse events warrant vigilance, particularly in vulnerable patient populations. GLP-1 RAs show emerging signals for cancer prevention and treatment, but their therapeutic application in oncology should proceed cautiously. Future research must prioritize well-designed, adequately powered cancer-focused RCTs that evaluate both efficacy and safety over extended periods.<\/jats:p>","DOI":"10.1007\/s11739-026-04458-z","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:09:49Z","timestamp":1783444189000},"page":"2787-2798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of GLP-1 receptor agonists in the prevention and treatment of obesity-related cancer"],"prefix":"10.1007","volume":"21","author":[{"given":"Giovanna","family":"Muscogiuri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guendalina","family":"Del Vecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Colangeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-7814","authenticated-orcid":false,"given":"Valeria","family":"Guglielmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Sbraccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Colao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"4458_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102782","volume":"75","author":"N Alfaris","year":"2024","unstructured":"Alfaris N, Waldrop S, Johnson V, Boaventura B, Kendrick K, Stanford FC (2024) GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review. 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