{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:05:04Z","timestamp":1785150304750,"version":"3.55.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF16OC0022586"],"award-info":[{"award-number":["NNF16OC0022586"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danmarks Grundforskningsfond","doi-asserted-by":"publisher","award":["DNRF148"],"award-info":[{"award-number":["DNRF148"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastroenterol"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1007\/s00535-022-01896-2","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T21:32:16Z","timestamp":1656797536000},"page":"761-769","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6880-5759","authenticated-orcid":false,"given":"Kristine H.","family":"Allin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla B.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke K.","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine","family":"Jess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"key":"1896_CR1","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","volume":"389","author":"J Torres","year":"2017","unstructured":"Torres J, Mehandru S, Colombel JF, et al. Crohn\u2019s disease. Lancet. 2017;389:1741\u201355.","journal-title":"Lancet"},{"key":"1896_CR2","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1016\/S0140-6736(16)32126-2","volume":"389","author":"R Ungaro","year":"2017","unstructured":"Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet. 2017;389:1756\u201370.","journal-title":"Lancet"},{"key":"1896_CR3","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/nrgastro.2017.110","volume":"14","author":"HSP de Souza","year":"2017","unstructured":"de Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017;14:739\u201349.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"1896_CR4","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1136\/gutjnl-2018-317572","volume":"69","author":"O Olen","year":"2020","unstructured":"Olen O, Askling J, Sachs MC, et al. Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964\u20132014. Gut. 2020;69:453\u201361.","journal-title":"Gut"},{"key":"1896_CR5","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.2337\/db14-1225","volume":"64","author":"SB Vasamsetti","year":"2015","unstructured":"Vasamsetti SB, Karnewar S, Kanugula AK, et al. Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes. 2015;64:2028\u201341.","journal-title":"Diabetes"},{"key":"1896_CR6","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1124\/jpet.109.164970","volume":"334","author":"M Arai","year":"2010","unstructured":"Arai M, Uchiba M, Komura H, et al. Metformin, an antidiabetic agent, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro. J Pharm Exp Ther. 2010;334:206\u201313.","journal-title":"J Pharm Exp Ther"},{"key":"1896_CR7","doi-asserted-by":"publisher","first-page":"23246","DOI":"10.1074\/jbc.M114.577908","volume":"289","author":"J Kim","year":"2014","unstructured":"Kim J, Kwak HJ, Cha JY, et al. Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction. J Biol Chem. 2014;289:23246\u201355.","journal-title":"J Biol Chem"},{"key":"1896_CR8","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1007\/s00125-008-1053-5","volume":"51","author":"CJ Bailey","year":"2008","unstructured":"Bailey CJ, Wilcock C, Scarpello JH. Metformin and the intestine. Diabetologia. 2008;51:1552\u20133.","journal-title":"Diabetologia"},{"key":"1896_CR9","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature15766","volume":"528","author":"K Forslund","year":"2015","unstructured":"Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262\u20136.","journal-title":"Nature"},{"key":"1896_CR10","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1007\/s00125-019-4848-7","volume":"62","author":"T Bryrup","year":"2019","unstructured":"Bryrup T, Thomsen CW, Kern T, et al. Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study. Diabetologia. 2019;62:1024\u201335.","journal-title":"Diabetologia"},{"key":"1896_CR11","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2337\/dc16-1324","volume":"40","author":"J de la Cuesta-Zuluaga","year":"2017","unstructured":"de la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, et al. Metformin is associated with higher relative abundance of mucin-degrading akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care. 2017;40:54\u201362.","journal-title":"Diabetes Care"},{"key":"1896_CR12","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1136\/gutjnl-2012-303839","volume":"63","author":"NR Shin","year":"2014","unstructured":"Shin NR, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63:727\u201335.","journal-title":"Gut"},{"key":"1896_CR13","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nm.4345","volume":"23","author":"H Wu","year":"2017","unstructured":"Wu H, Esteve E, Tremaroli V, et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017;23:850\u20138.","journal-title":"Nat Med"},{"key":"1896_CR14","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41579-019-0213-6","volume":"17","author":"M Schirmer","year":"2019","unstructured":"Schirmer M, Garner A, Vlamakis H, et al. Microbial genes and pathways in inflammatory bowel disease. Nat Rev Microbiol. 2019;17:497\u2013511.","journal-title":"Nat Rev Microbiol"},{"key":"1896_CR15","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1053\/j.gastro.2019.11.294","volume":"158","author":"R Pittayanon","year":"2020","unstructured":"Pittayanon R, Lau JT, Leontiadis GI, et al. Differences in gut microbiota in patients with vs without inflammatory bowel diseases: a systematic review. Gastroenterology. 2020;158:930\u201346.e1.","journal-title":"Gastroenterology."},{"key":"1896_CR16","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1136\/gutjnl-2019-320105","volume":"69","author":"L Wang","year":"2020","unstructured":"Wang L, Tang L, Feng Y, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8(+) T cells in mice. Gut. 2020;69:1988\u201397.","journal-title":"Gut"},{"key":"1896_CR17","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1093\/ecco-jcc\/jjaa136","volume":"15","author":"CH Tseng","year":"2021","unstructured":"Tseng CH. Metformin use is associated with a lower risk of inflammatory bowel disease in patients with type 2 diabetes mellitus. J Crohns Colitis. 2021;15:64\u201373.","journal-title":"J Crohns Colitis"},{"key":"1896_CR18","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.2337\/dc12-0788","volume":"35","author":"S Suissa","year":"2012","unstructured":"Suissa S, Azoulay L. Metformin and the risk of cancer: time-related biases in observational studies. Diabetes Care. 2012;35:2665\u201373.","journal-title":"Diabetes Care"},{"key":"1896_CR19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1177\/1403494811401482","volume":"39","author":"E Lynge","year":"2011","unstructured":"Lynge E, Sandegaard JL, Rebolj M. The Danish national patient register. Scand J Public Health. 2011;39:30\u20133.","journal-title":"Scand J Public Health"},{"key":"1896_CR20","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1177\/1403494810394717","volume":"39","author":"HW Kildemoes","year":"2011","unstructured":"Kildemoes HW, Sorensen HT, Hallas J. The Danish national prescription registry. Scand J Public Health. 2011;39:38\u201341.","journal-title":"Scand J Public Health"},{"key":"1896_CR21","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1177\/1403494810394715","volume":"39","author":"VM Jensen","year":"2011","unstructured":"Jensen VM, Rasmussen AW. Danish education registers. Scand J Public Health. 2011;39:91\u20134.","journal-title":"Scand J Public Health"},{"key":"1896_CR22","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","volume":"29","author":"M Schmidt","year":"2014","unstructured":"Schmidt M, Pedersen L, Sorensen HT. The Danish civil registration system as a tool in epidemiology. Eur J Epidemiol. 2014;29:541\u20139.","journal-title":"Eur J Epidemiol"},{"key":"1896_CR23","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1002\/cam4.306","volume":"3","author":"M Cardel","year":"2014","unstructured":"Cardel M, Jensen SM, Pottegard A, et al. Long-term use of metformin and colorectal cancer risk in type II diabetics: a population-based case-control study. Cancer Med. 2014;3:1458\u201366.","journal-title":"Cancer Med"},{"key":"1896_CR24","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","volume":"390","author":"SC Ng","year":"2018","unstructured":"Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2018;390:2769\u201378.","journal-title":"Lancet"},{"key":"1896_CR25","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1093\/ije\/dyx046","volume":"46","author":"RE Farmer","year":"2017","unstructured":"Farmer RE, Ford D, Forbes HJ, et al. Metformin and cancer in type 2 diabetes: a systematic review and comprehensive bias evaluation. Int J Epidemiol. 2017;46:728\u201344.","journal-title":"Int J Epidemiol"},{"key":"1896_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105425","volume":"165","author":"YB Wang","year":"2021","unstructured":"Wang YB, Tan LM, Luo L, et al. Immortal time bias exaggerates the effect of metformin on the risk of gastric cancer: a meta-analysis. Pharm Res. 2021;165: 105425.","journal-title":"Pharm Res"},{"key":"1896_CR27","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1093\/aje\/kwm324","volume":"167","author":"S Suissa","year":"2008","unstructured":"Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol. 2008;167:492\u20139.","journal-title":"Am J Epidemiol"},{"key":"1896_CR28","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3109\/00365529609031980","volume":"31","author":"K Fonager","year":"1996","unstructured":"Fonager K, Sorensen HT, Rasmussen SN, et al. Assessment of the diagnoses of crohn\u2019s disease and ulcerative colitis in a Danish hospital information system. Scand J Gastroenterol. 1996;31:154\u20139.","journal-title":"Scand J Gastroenterol"},{"key":"1896_CR29","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1080\/00365521.2020.1807598","volume":"55","author":"B Lo","year":"2020","unstructured":"Lo B, Vind I, Vester-Andersen M, et al. Validation of ulcerative colitis and crohn\u2019s disease and their phenotypes in the Danish national patient registry using a population-based cohort. Scand J Gastroenterol. 2020;55:1171\u20135.","journal-title":"Scand J Gastroenterol"}],"container-title":["Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-022-01896-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00535-022-01896-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-022-01896-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T19:14:04Z","timestamp":1664478844000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00535-022-01896-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,2]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["1896"],"URL":"https:\/\/doi.org\/10.1007\/s00535-022-01896-2","relation":{},"ISSN":["0944-1174","1435-5922"],"issn-type":[{"value":"0944-1174","type":"print"},{"value":"1435-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,2]]},"assertion":[{"value":"5 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Danish Data Protection Agency, and data were analyzed on a secure research server at Statistics Denmark. Ethical approval is not required for registry-based research in Denmark.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}