{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:26:21Z","timestamp":1792589181840,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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":[[2016,5]]},"abstract":"\n Aims<\/jats:title>\n Liraglutide 3.0\u2009mg, an acylated GLP\u20101 analogue approved for weight management, lowers body weight through decreased energy intake. We conducted exposure\u2010response analyses to provide important information on individual responses to given drug doses, reflecting inter\u2010individual variations in drug metabolism, absorption and excretion.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We report efficacy and safety responses across a wide range of exposure levels, using data from one phase\n II<\/jats:styled-content>\n (liraglutide doses 1.2, 1.8, 2.4 and 3.0\u2009mg), and two phase\n IIIa<\/jats:styled-content>\n [\n SCALE O<\/jats:styled-content>\n besity and\n P<\/jats:styled-content>\n rediabetes (3.0\u2009mg);\n SCALE D<\/jats:styled-content>\n iabetes (1.8; 3.0\u2009mg)] randomized, placebo\u2010controlled trials (n\u2009=\u20094372).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n There was a clear exposure\u2013weight loss response. Weight loss increased with greater exposure and appeared to level off at the highest exposures associated with liraglutide 3.0\u2009mg in most individuals, but did not fully plateau in men. In individuals with overweight\/obesity and comorbid type 2 diabetes, there was a clear exposure\u2013glycated haemoglobin (\n HbA1c<\/jats:styled-content>\n ) relationship.\n HbA1c<\/jats:styled-content>\n reduction increased with higher plasma liraglutide concentration (plateauing at \u223c21\u2009\n nM<\/jats:styled-content>\n ); however, for individuals with baseline\n HbA1c<\/jats:styled-content>\n >8.5%,\n HbA1c<\/jats:styled-content>\n reduction did not fully plateau. No exposure\u2013response relationship was identified for any safety outcome, with the exception of gastrointestinal adverse events (\n AEs<\/jats:styled-content>\n ). Individuals with gallbladder\n AEs<\/jats:styled-content>\n , acute pancreatitis or malignant\/breast\/benign colorectal neoplasms did not have higher liraglutide exposure compared with the overall population.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These analyses support the use of liraglutide 3.0\u2009mg for weight management in all subgroups investigated; weight loss increased with higher drug exposure, with no concomitant deterioration in safety\/tolerability besides previously known gastrointestinal side effects.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12639","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T02:28:44Z","timestamp":1454380124000},"page":"491-499","source":"Crossref","is-referenced-by-count":97,"title":["Exposure\u2013response analyses of liraglutide 3.0\u2009mg for weight management"],"prefix":"10.1111","volume":"18","author":[{"given":"J. P. H.","family":"Wilding","sequence":"first","affiliation":[{"name":"Department of Obesity and Endocrinology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. V.","family":"Overgaard","sequence":"additional","affiliation":[{"name":"Medical Affairs, GLP\u20101 and Obesity Novo Nordisk A\/S S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. V.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Medical Affairs, GLP\u20101 and Obesity Novo Nordisk A\/S S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. B.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Medical Affairs, GLP\u20101 and Obesity Novo Nordisk A\/S S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. W.","family":"le Roux","sequence":"additional","affiliation":[{"name":"Diabetes Complications Research Centre, Conway Institute University College Dublin Dublin Ireland"},{"name":"Investigative Science Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb00650.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/379069a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI990"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990111)403:2<261::AID-CNE8>3.0.CO;2-5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801627"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.K10E-077"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.07.003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2212-10.2011"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9909645"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00401145"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61375-1"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.9676"},{"key":"e_1_2_7_14_1","unstructured":"FDA Briefing Document for Liraglutide NDA 206321.Endocrinologic and Metabolic Drugs Advisory Committee meeting 11 September2014. 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