{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:48:59Z","timestamp":1792676939972,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Metformin and glucagon\u2010like peptide\u20101 receptor agonists (\n GLP<\/jats:styled-content>\n \u20101\n RAs<\/jats:styled-content>\n ) may reduce the risk of adiposity\u2010related cancers in patients with type 2 diabetes (\n T2D<\/jats:styled-content>\n ). The potential synergistic effects of these treatments on cancer incidence remain unclear, considering their distinct biological mechanisms and their associated effects on body weight.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A retrospective cohort analysis was conducted using a large global database (\n TriNetX<\/jats:styled-content>\n ) of patients with\n T2D<\/jats:styled-content>\n . Three cohorts: single agent use with metformin or\n GLP<\/jats:styled-content>\n \u20101\n RAs<\/jats:styled-content>\n , and dual\/combination metformin\/\n GLP<\/jats:styled-content>\n \u20101\n RA<\/jats:styled-content>\n use, were compared with a reference group treated with\n DPP4<\/jats:styled-content>\n inhibitors (\n DPP4i<\/jats:styled-content>\n ). Propensity score matching (1:1) was applied to control for confounders. Cancer incidence and all cause mortality were assessed over 5\u2009years of follow up.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After matching, metformin and\n GLP<\/jats:styled-content>\n \u20101\n RA<\/jats:styled-content>\n treatment were both associated with a lower risk of all adiposity\u2010related cancers and all\u2010cause mortality; the latter was associated with greater reductions in both. Cancer rates were (hazard ratio) 0.96 [95%\n CI<\/jats:styled-content>\n 0.92, 0.99] and 0.86 [0.82, 0.89], while mortality rates were 0.78 [0.76, 0.80] and 0.61 [0.59, 0.63] for metformin and\n GLP<\/jats:styled-content>\n \u20101\n RA<\/jats:styled-content>\n , respectively. Dual therapy showed the strongest association with lower cancer incidence (0.61 [0.57, 0.65]) and mortality (0.33 [0.32, 0.35]). Results were more significant in younger, male patients with obesity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In patients with T2D, dual metformin and GLP\u20101 RA treatment was associated with a 39% lower incidence of adiposity\u2010related cancers and a 67% lower mortality, with a striking impact on cancer\u2010related outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.70267","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T10:44:35Z","timestamp":1762166675000},"page":"946-959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Synergistic associations of metformin and\n GLP<\/scp>\n \u20101 receptor agonist use with adiposity\u2010related cancer incidence in people living with type 2 diabetes"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex 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Liverpool UK"},{"name":"Metabolism & Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa J.","family":"Hydes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine University of Liverpool Liverpool UK"},{"name":"Metabolism & Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-7369","authenticated-orcid":false,"given":"Matthew","family":"Anson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine University of Liverpool Liverpool UK"},{"name":"Metabolism & Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine University of Liverpool Liverpool UK"},{"name":"Metabolism & Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust Liverpool Merseyside UK"},{"name":"Visiting Fellow, Centre for Biomechanics and Rehabilitation Technologies Staffordshire University Stoke\u2010on\u2010Trent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine University of Liverpool Liverpool UK"},{"name":"Metabolism & Nutrition 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