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Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia\/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A retrospective, observational,\u00a0multicenter\u00a0study in 197 acromegalic patients, receiving\/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In general, the occurrence of secondary neoplasia among our patients was significantly (<jats:italic>p<\/jats:italic>V\u2009=\u20090.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged\u2009&gt;\u200950\u00a0years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (<jats:italic>p<\/jats:italic>V\u2009=\u20090.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10147-021-01895-y","type":"journal-article","created":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T13:02:50Z","timestamp":1615640570000},"page":"1015-1021","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The prevalence of secondary neoplasms in acromegalic patients: possible preventive and\/or protective role of metformin"],"prefix":"10.1007","volume":"26","author":[{"given":"Denise","family":"Costa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Lauretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"De Vito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Scaroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialuisa","family":"Appetecchia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1216-2034","authenticated-orcid":false,"given":"Patrizia","family":"Gargiulo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"issue":"1","key":"1895_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1210\/er.2002-0022","volume":"25","author":"A Colao","year":"2004","unstructured":"Colao A, Ferone D, Marzullo P et al (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. 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