{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:11:49Z","timestamp":1789726309930,"version":"4.0.1"},"reference-count":10,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To describe the changes in serum levels of calcitonin in liraglutide- and placebo-treated patients in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results\u2014A Long Term Evaluation (LEADER) trial over a 3.5\u20135-year period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Patients (n = 9,340) with type 2 diabetes and high risk for cardiovascular events were randomized 1:1 to liraglutide or placebo. We analyzed calcitonin levels, thyroid and C-cell adverse events, and neoplasms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>At 36 months, patients randomized to liraglutide versus placebo showed no evidence of increase in calcitonin concentrations in male (estimated treatment ratio [ETR] 1.03 [95% CI 1.00, 1.06]; P = 0.068) and female (ETR 1.00 [95% CI 0.97, 1.02]; P = 0.671) subgroups. There were no episodes of C-cell hyperplasia or medullary thyroid carcinoma in liraglutide-treated patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>There was no evidence of a difference in calcitonin concentrations between the liraglutide and placebo groups, and no C-cell malignancies occurred in the liraglutide group.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc17-1956","type":"journal-article","created":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T01:10:33Z","timestamp":1514337033000},"page":"620-622","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":62,"title":["No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial"],"prefix":"10.2337","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct01179048","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01179048","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9691-7619","authenticated-orcid":false,"given":"Laszlo","family":"Heged\u00fcs","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven I.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Michael","family":"Tuttle","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernt J.","family":"von Scholten","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie D.","family":"Karsb\u00f8l","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert H.","family":"Daniels","sequence":"additional","affiliation":[{"name":"Thyroid Unit and Cancer Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the LEADER Publication Committee on behalf of the LEADER Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2017,12,26]]},"reference":[{"key":"2022031301223855700_B1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ncpendmet1023","article-title":"Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls","volume":"5","author":"Costante","year":"2009","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"2022031301223855700_B2","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1002\/cncr.28858","article-title":"Medical management of metastatic medullary thyroid cancer","volume":"120","author":"Maxwell","year":"2014","journal-title":"Cancer"},{"key":"2022031301223855700_B3","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1677\/ERC-09-0136","article-title":"Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer","volume":"16","author":"Machens","year":"2009","journal-title":"Endocr Relat Cancer"},{"key":"2022031301223855700_B4","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/dom.12444","article-title":"LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial: preliminary observations","volume":"17","author":"Daniels","year":"2015","journal-title":"Diabetes Obes Metab"},{"key":"2022031301223855700_B5","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.beem.2008.09.008","article-title":"Routine serum calcitonin measurement in the evaluation of thyroid nodules","volume":"22","author":"Elisei","year":"2008","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2022031301223855700_B6","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1210\/en.2009-1272","article-title":"Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation","volume":"151","author":"Bjerre Knudsen","year":"2010","journal-title":"Endocrinology"},{"key":"2022031301223855700_B7","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1210\/en.2011-1864","article-title":"GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation","volume":"153","author":"Madsen","year":"2012","journal-title":"Endocrinology"},{"key":"2022031301223855700_B8","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1210\/jc.2010-2318","article-title":"GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide","volume":"96","author":"Heged\u00fcs","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031301223855700_B9","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"2022031301223855700_B10","doi-asserted-by":"crossref","first-page":"823.e5","DOI":"10.1016\/j.ahj.2013.07.012","article-title":"Design of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial","volume":"166","author":"Marso","year":"2013","journal-title":"Am Heart J"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc17-1956","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/41\/3\/620\/552567\/dc171956.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/41\/3\/620\/552567\/dc171956.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T05:09:54Z","timestamp":1647148194000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/41\/3\/620\/36613\/No-Evidence-of-Increase-in-Calcitonin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,26]]},"references-count":10,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,12,26]]},"published-print":{"date-parts":[[2018,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc17-1956","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,26]]}}}