{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:42:32Z","timestamp":1791042152364,"version":"4.1.0"},"reference-count":51,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:p>The discovery of leptin in 1994 was a seminal event in obesity research. It helped to establish that body weight is tightly regulated by a complex neurohormonal feedback system and that obesity should be viewed as a disorder with a strong biological basis rather than simply the result of poor lifestyle choices and lack of willpower.<\/jats:p>\n                  <jats:p>Leptin, secreted from adipocytes, acts as a prototypic long-term (tonic) adiposity signal. Although nonclinical and clinical studies have provided unequivocal evidence that leptin plays a unique, pivotal role in body weight regulation, efforts to develop recombinant leptin (metreleptin) as a monotherapy for obesity have proven unsuccessful. Amylin, secreted from pancreatic \u03b2-cells, fulfills the criteria for a short-term (episodic) satiety signal. The amylin analog pramlintide elicits sustained reductions in food intake and body weight in obese rodents and humans.<\/jats:p>\n                  <jats:p>A translational research program aimed at elucidating the interaction between different islet-, gut-, and adipocyte-derived hormones led to the discovery that combined amylin\/leptin agonism induces marked, synergistic, fat-specific weight loss in leptin-resistant diet-induced obese rodents. In obese humans, combination treatment with pramlintide\/metreleptin led to an approximately 13% weight loss after 24 weeks, significantly more than after treatment with pramlintide or metreleptin alone.<\/jats:p>\n                  <jats:p>Collectively, these findings suggest that combined amylin\/leptin agonism may have therapeutic utility as part of an integrated, neurohormonal approach to obesity pharmacotherapy.<\/jats:p>","DOI":"10.2310\/jim.0b013e3181b91911","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T09:10:57Z","timestamp":1462957857000},"page":"777-783","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["It Takes Two to Tango: Combined Amylin\/Leptin Agonism as a Potential Approach to Obesity Drug Development"],"prefix":"10.1177","volume":"57","author":[{"given":"Jean L.","family":"Chan","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals, Inc, San Diego, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Roth","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, Inc, San Diego, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weyer","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, Inc, San Diego, 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