{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:27:00Z","timestamp":1770740820891,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T00:00:00Z","timestamp":1486598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"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":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Sustained exogenous stimulation of a hormone\u2010specific receptor can affect endogenous hormonal regulation. In this context, little is known about the impact of chronic treatment with glucagon\u2010like peptide\u20101 (\n GLP<\/jats:styled-content>\n \u20101) agonists on the endogenous\n GLP<\/jats:styled-content>\n \u20101 response. We therefore evaluated the impact of chronic liraglutide therapy on endogenous\n GLP<\/jats:styled-content>\n \u20101 and glucose\u2010dependent insulinotropic polypeptide (\n GIP<\/jats:styled-content>\n ) response to an oral glucose challenge. A total of 51 people with type 2 diabetes of 2.6\u2009\u00b1\u20091.9\u2009years\u2019 duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48\u2009weeks, with an oral glucose tolerance test (\n OGTT<\/jats:styled-content>\n ) every 12\u2009weeks.\n GLP<\/jats:styled-content>\n \u20101 and\n GIP<\/jats:styled-content>\n responses were assessed according to their respective area under the curve (\n AUC<\/jats:styled-content>\n ) from measurements taken at 0, 30, 60, 90 and 120\u2009minutes during each\n OGTT<\/jats:styled-content>\n . There were no differences in\n \n AUC\n GIP<\/jats:sub>\n <\/jats:styled-content>\n between the groups. By contrast, although fasting\n GLP<\/jats:styled-content>\n \u20101 was unaffected, the liraglutide arm had ~2\u2010fold higher\n \n AUC\n GLP<\/jats:sub>\n <\/jats:styled-content>\n \u20101<\/jats:sub>\n at 12\u2009weeks (\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.001), 24\u2009weeks (\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009<\u2009.001), 36\u2009weeks (\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009=\u2009.03) and 48\u2009weeks (\n \n P<\/jats:styled-content>\n <\/jats:italic>\n \u2009=\u2009.03), as compared with placebo. Thus, chronic liraglutide therapy induces a previously unrecognized, robust and durable enhancement of the endogenous\n GLP<\/jats:styled-content>\n \u20101 response, highlighting the need for further study of the long\u2010term effects of incretin mimetics on\n L<\/jats:styled-content>\n \u2010cell physiology.\n <\/jats:p>","DOI":"10.1111\/dom.12858","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T01:02:41Z","timestamp":1486602161000},"page":"744-748","source":"Crossref","is-referenced-by-count":16,"title":["Chronic liraglutide therapy induces an enhanced endogenous glucagon\u2010like peptide\u20101 secretory response in early type 2 diabetes"],"prefix":"10.1111","volume":"19","author":[{"given":"Caroline K.","family":"Kramer","sequence":"first","affiliation":[{"name":"Leadership Sinai Centre for Diabetes Mount Sinai Hospital Toronto Canada"},{"name":"Department of Medicine, Division of Endocrinology University of Toronto Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes Mount Sinai Hospital Toronto Canada"},{"name":"Department of Medicine, Division of Endocrinology University of Toronto Toronto Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haysook","family":"Choi","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes Mount Sinai Hospital Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip W.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology University of Toronto Toronto Canada"},{"name":"Keenan Research Centre for Biomedical Science of St. Michael's Hospital Toronto Canada"},{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-027X","authenticated-orcid":false,"given":"Ravi","family":"Retnakaran","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes Mount Sinai Hospital Toronto Canada"},{"name":"Department of Medicine, Division of Endocrinology University of Toronto Toronto Canada"},{"name":"Lunenfeld\u2010Tanenbaum Research Institute Mount Sinai Hospital Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01658.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1896-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-0893"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2591"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00447.2013"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01254.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01129.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2001.281.1.E155"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12533"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2489"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801655"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.9.1640"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.38.6.916"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS19980308"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021873"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2725"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12858","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.12858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:21:22Z","timestamp":1761862882000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.12858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,9]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1111\/dom.12858"],"URL":"https:\/\/doi.org\/10.1111\/dom.12858","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,9]]}}}