{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:42:52Z","timestamp":1781174572954,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848082004"],"award-info":[{"award-number":["848082004"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the effect of metformin on non\u2010muscle\u2010invasive bladder cancer (NMIBC) marker lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>A phase II, open\u2010label, multicentre, marker lesion trial using oral metformin in patients with primary or recurrent, multiple, low\u2010grade Ta\u2010T1 NMIBC was conducted. After transurethral resection for histological confirmation, leaving one tumour as a marker lesion, 11 patients were treated with oral metformin up to 3000\u2009mg per day for 3\u2009months. Reported outcomes included response of the marker lesion, safety of metformin, quality of life and pharmacological and immunohistochemical examinations of the mechanism of action of metformin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One complete response and one partial response were observed. In the other nine patients, the marker lesion remained, while five of these patients also developed new Ta low\u2010grade lesions. Diarrhoea grade \u2264\u20092 was the most common adverse event (AE), observed in nine out of 11 patients. No serious AEs related to study treatment occurred. Metformin concentrations in the urine were significantly higher than metformin levels in the blood. Immunohistochemical analysis before and after treatment showed no difference in expression of markers associated with the mechanism of metformin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We did not find conclusive evidence for the hypothesis of an antitumour effect of metformin in bladder cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bju.16767","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T19:55:32Z","timestamp":1747943732000},"page":"738-746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A study of oral metformin for the intravesical treatment of non\u2010muscle\u2010invasive bladder cancer"],"prefix":"10.1111","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-9512","authenticated-orcid":false,"given":"Jons W.","family":"van Hattum","sequence":"first","affiliation":[{"name":"Department of Urology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam Cancer Treatment and Quality of Life  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3118-5373","authenticated-orcid":false,"given":"Marinka J.","family":"Remmelink","sequence":"additional","affiliation":[{"name":"Department of Urology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam Cancer Treatment and Quality of Life  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0425-6479","authenticated-orcid":false,"given":"Sieb T.","family":"Nuijens","sequence":"additional","affiliation":[{"name":"Department of Urology Radboud University Medical Center  Nijmegen The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben Max","family":"de Ruiter","sequence":"additional","affiliation":[{"name":"Department of Urology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam Cancer Treatment and Quality of Life  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit K.J.","family":"Hooijer","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorg R.","family":"Oddens","sequence":"additional","affiliation":[{"name":"Department of Urology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Cancer Center Amsterdam Cancer Treatment and Quality of Life  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Dilara","family":"Savci\u2010Heijink","sequence":"additional","affiliation":[{"name":"Department of Pathology Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Mathot","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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