{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T01:33:29Z","timestamp":1777253609623,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1ZIADK075035"],"award-info":[{"award-number":["1ZIADK075035"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1ZIADK043006"],"award-info":[{"award-number":["1ZIADK043006"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Z01\u2010BC 006150"],"award-info":[{"award-number":["Z01\u2010BC 006150"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Metformin is a widely prescribed medication in the management of type 2 diabetes mellitus, and numerous epidemiological studies have indicated an association between metformin use and a reduced risk of certain cancers in diabetic populations. However, evidence supporting a role for metformin in cancer prevention remains inconclusive. Exploring tumor\u2010preventive strategies may be particularly relevant for inherited cancer syndromes with high tumor penetrance such as pancreatic neuroendocrine tumors (PNETs) associated with multiple endocrine neoplasia type 1 (MEN1). MEN1 is caused by germline pathogenic variants in the tumor suppressor gene\n                    <jats:italic>MEN1<\/jats:italic>\n                    , and mouse models with\n                    <jats:italic>Men1<\/jats:italic>\n                    gene loss also develop PNETs. To evaluate whether metformin is associated with altered PNET outcomes in MEN1, we performed a retrospective analysis of MEN1 patients with PNETs, incorporating detailed clinical exposure data and complemented this analysis with a preclinical study using pancreatic islet \u03b2\u2010cell\u2010specific\n                    <jats:italic>Men1<\/jats:italic>\n                    \u2010knockout mice treated with metformin. In the clinical cohort, metformin exposure varied substantially with respect to timing and duration relative to PNET diagnosis. No statistically significant association between metformin use and overall survival or metastatic disease was detected in this limited cohort. In the mouse model, treatment with 2\u2009mg\/mL metformin in drinking water initiated post\u2010weaning did not prevent PNET development, nor did it alter circulating insulin or glucose levels. These findings indicate that, under the dosing and exposure conditions examined, metformin was not associated with measurable tumor\u2010protective or tumor\u2010preventive effects in MEN1\u2010related PNETs. The study highlights important methodological considerations, including exposure timing and statistical power, and supports the need for prospective studies initiating metformin prior to tumor development in genetically predisposed populations.\n                  <\/jats:p>","DOI":"10.1111\/jne.70166","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T06:07:34Z","timestamp":1774505254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of metformin on pancreatic neuroendocrine tumors of multiple endocrine neoplasia type 1"],"prefix":"10.1111","volume":"38","author":[{"given":"Serguei V.","family":"Kozlov","sequence":"first","affiliation":[{"name":"Center for Advanced Preclinical Research, Frederick National Lab for Cancer Research, Center for Cancer Research National Cancer Institute  Frederick Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7557-3191","authenticated-orcid":false,"given":"Sunita K.","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa M.","family":"Guerin","sequence":"additional","affiliation":[{"name":"Center for Advanced Preclinical Research, Frederick National Lab for Cancer Research, Center for Cancer Research National Cancer Institute  Frederick Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendi Custer","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Center for Advanced Preclinical Research, Frederick National Lab for Cancer Research, Center for Cancer Research National Cancer Institute  Frederick Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura L.","family":"Bassel","sequence":"additional","affiliation":[{"name":"Center for Advanced Preclinical Research, Frederick National Lab for Cancer Research, Center for Cancer Research National Cancer Institute  Frederick Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akua","family":"Graf","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-3340","authenticated-orcid":false,"given":"Smita","family":"Jha","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland 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