{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:19:11Z","timestamp":1792441151027,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T00:00:00Z","timestamp":1346889600000},"content-version":"vor","delay-in-days":1101,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:p>The neurohormonal control of body weight involves a complex interplay between long\u2010term adiposity signals (e.g., leptin), and short\u2010term satiation signals (e.g., amylin). In diet\u2010induced obese (DIO) rodents, amylin\/leptin combination treatment led to marked, synergistic, fat\u2010specific weight loss. To evaluate the weight\u2010lowering effect of combined amylin\/leptin agonism (with pramlintide\/metreleptin) in human obesity, a 24\u2010week, randomized, double\u2010blind, active\u2010drug\u2010controlled, proof\u2010of\u2010concept study was conducted in obese or overweight subjects (<jats:italic>N<\/jats:italic> = 177; 63% female; 39 \u00b1 8 years; BMI 32.0 \u00b1 2.1 kg\/m<jats:sup>2<\/jats:sup>; 93.3 \u00b1 13.2 kg; mean \u00b1 s.d.). After a 4\u2010week lead\u2010in period with pramlintide (180 \u00b5g b.i.d. for 2 weeks, 360 \u00b5g b.i.d. thereafter) and diet (40% calorie deficit), subjects achieving 2\u20138% weight loss were randomized 1:2:2 to 20 weeks of treatment with metreleptin (5 mg b.i.d.), pramlintide (360 \u00b5g b.i.d.), or pramlintide\/metreleptin (360 \u00b5g\/5 mg b.i.d.). Combination treatment with pramlintide\/metreleptin led to significantly greater weight loss from enrollment to week 20 (\u221212.7 \u00b1 0.9%; least squares mean \u00b1 s.e.) than treatment with pramlintide (\u22128.4 \u00b1 0.9%; <jats:italic>P<\/jats:italic> &lt; 0.001) or metreleptin (\u22128.2 \u00b1 1.3%; <jats:italic>P<\/jats:italic> &lt; 0.01) alone (evaluable, <jats:italic>N<\/jats:italic> = 93). The greater reduction in body weight was significant as early as week 4, and weight loss continued throughout the study, without evidence of a plateau. The most common adverse events with pramlintide\/metreleptin were injection site events and nausea, which were mostly mild to moderate and decreased over time. These results support further development of pramlintide\/metreleptin as a novel, integrated neurohormonal approach to obesity pharmacotherapy.<\/jats:p>","DOI":"10.1038\/oby.2009.184","type":"journal-article","created":{"date-parts":[[2009,6,11]],"date-time":"2009-06-11T14:27:11Z","timestamp":1244730431000},"page":"1736-1743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":298,"title":["Enhanced Weight Loss With Pramlintide\/Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy"],"prefix":"10.1002","volume":"17","author":[{"given":"Eric","family":"Ravussin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma","family":"Shringarpure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy E.","family":"Koda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,6]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109951"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2006.275"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/9781420051452-22"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/157339908784220741"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909163411204"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215693"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/43185"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.16.1568"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450053174596"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2006.04.001"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00217.2007"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2003"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0029"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00474.2002"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199503093321001"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25977"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.5.8628"},{"key":"e_1_2_7_19_2","unstructured":"KissileffHR ThorntonJC TorresMet al.Maintenance of reduced body weight in humans is associated with leptin\u2010reversible changes in appetite\u2010related ratings [abstract]. 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