{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:02:41Z","timestamp":1780534961797,"version":"3.54.1"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T00:00:00Z","timestamp":1346889600000},"content-version":"vor","delay-in-days":1863,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective:<\/jats:italic>Central counter\u2010regulatory mechanisms, including those related to the orexigenic hormone neuropeptide Y (NPY), may limit the weight loss observed with conventional pharmacological monotherapy. This study evaluated whether blockade of the NPY Y5 receptor (NPY5R) with the selective antagonist MK\u20100557 potentiates sibutramine and orlistat weight loss effects.<\/jats:p><jats:p><jats:italic>Research Methods and Procedures:<\/jats:italic>Obese patients (497, BMI 30 to 43 kg\/m<jats:sup>2<\/jats:sup>) were randomized to 1 of 5 treatment arms [placebo,<jats:italic>n<\/jats:italic>= 101; sibutramine 10 mg\/d,<jats:italic>n<\/jats:italic>= 100; MK\u20100557 1 mg\/d plus sibutramine 10 mg\/d,<jats:italic>n<\/jats:italic>= 98; orlistat 120 mg TID,<jats:italic>n<\/jats:italic>= 99; MK\u20100557 1 mg\/d plus orlistat 120 mg TID,<jats:italic>n<\/jats:italic>= 99] in conjunction with a hypocaloric diet for 24 weeks. The all\u2010patients\u2010treated population, imputing missing data using last observation carried forward, was used to assess weight loss from baseline.<\/jats:p><jats:p><jats:italic>Results:<\/jats:italic>The study was completed by 71% of patients in placebo, 76% in sibutramine alone, 79% in MK\u20100557 + sibutramine, 69% in orlistat alone, and 76% in MK\u20100557 + orlistat groups. Least squares (LS) mean difference [95% confidence interval (CI)] in weight change from baseline between MK\u20100557 + sibutramine and sibutramine alone was \u22120.1 (\u22121.6, 1.4) kg (<jats:italic>p<\/jats:italic>= 0.892) and between MK\u20100557 + orlistat and orlistat alone was \u22120.9 (\u22122.4, 0.6) kg (<jats:italic>p<\/jats:italic>= 0.250). Sibutramine alone induced a LS mean weight loss of \u22125.9 (\u22126.9, \u22124.9) kg vs. \u22124.6 (\u22125.7, \u22123.6) kg for orlistat (<jats:italic>p<\/jats:italic>= 0.097). There were no serious drug\u2010related adverse events and MK\u20100557 was well tolerated.<\/jats:p><jats:p><jats:italic>Discussion:<\/jats:italic>Blockade of the NPY5R with the potent antagonist MK\u20100557 did not significantly increase the weight loss efficacy of either orlistat or sibutramine monotherapy.<\/jats:p>","DOI":"10.1038\/oby.2007.242","type":"journal-article","created":{"date-parts":[[2008,7,17]],"date-time":"2008-07-17T22:35:42Z","timestamp":1216334142000},"page":"2027-2042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["NPY5R Antagonism Does Not Augment the Weight Loss Efficacy of Orlistat or Sibutramine"],"prefix":"10.1002","volume":"15","author":[{"given":"Ngozi","family":"Erondu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Addy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuja","family":"Mallick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret","family":"Musser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Gantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Proietto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Astrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Toubro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aila M.","family":"Rissannen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Tonstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith M.","family":"Gottesdiener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Amatruda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Heymsfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,6]]},"reference":[{"issue":"3","key":"e_1_2_7_2_2","first-page":"35","article-title":"Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase","volume":"11","author":"Hogan S.","year":"1987","journal-title":"Int J Obes"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.20.4.270.34882"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)52203-1"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(88)90260-3"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.5.3.633"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450053174550"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.164.9.994"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2004.00125.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-142-7-200504050-00012"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-277X.2004.00530.x"},{"key":"e_1_2_7_12_2","article-title":"Long\u2010term pharmacotherapy for obesity and overweight","volume":"3","author":"Padwal R.","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-115-1-427"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.20.1.68"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/35007534"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981228)402:4<435::AID-CNE1>3.0.CO;2-M"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81084-3"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/382168a0"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.42.26315"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4188"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000626200"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(00)00156-X"},{"key":"e_1_2_7_23_2","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/S0026-895X(24)12616-8","article-title":"Identification of potent and selective neuropeptide Y Y(1) receptor agonists with orexigenic activity in vivo","volume":"60","author":"Mullins D.","year":"2001","journal-title":"Mol Pharmacol"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(02)00034-4"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-0119"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm025513q"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510320103"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.3.7387"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.8.2441"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15659"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0698-722"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0698-718"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/381415a0"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1115524"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.08.002"},{"issue":"3","key":"e_1_2_7_36_2","first-page":"24","article-title":"A one\u2010year trial to assess the value of orlistat in the management of obesity","volume":"21","author":"James W. P.","year":"1997","journal-title":"Int J Obes Relat Metab Disord"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1550-8528.1995.tb00120.x"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-199206000-00002"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8510(90)90421-9"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1467-789X.2003.00109.x"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.620"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00841-D"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(96)00142-8"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(91)90007-C"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702633"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802475"},{"key":"e_1_2_7_47_2","unstructured":"Mashiko S. Ishihara A. Iwaasa H. et alAnti\u2010obesity effects of a novel Y5 antagonist in diet\u2010induced obese mice: combination with food restriction or sibutramine. Submitted."},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2004.09.006"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2004.00372.x"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-200027356"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.202.173"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-200027356"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1463-1326.2002.00181.x"},{"key":"e_1_2_7_54_2","first-page":"222","article-title":"Comparison of metabolic effects of orlistat and sibutramine treatment in Type 2 diabetic obese patients","volume":"17","author":"Derosa G.","year":"2004","journal-title":"Diabetes Nutr Metab"}],"container-title":["Obesity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Foby.2007.242","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/oby.2007.242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T02:11:38Z","timestamp":1738289498000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1038\/oby.2007.242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":53,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1038\/oby.2007.242"],"URL":"https:\/\/doi.org\/10.1038\/oby.2007.242","archive":["Portico"],"relation":{},"ISSN":["1930-7381","1930-739X"],"issn-type":[{"value":"1930-7381","type":"print"},{"value":"1930-739X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]},"assertion":[{"value":"2012-09-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}