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However, real\u2010world evidence remains limited. This study evaluates the long\u2010term effectiveness and safety of setmelanotide in patients who received treatment under a pre\u2010marketing early\u2010access authorization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This ongoing prospective monocentric cohort includes 17 patients with obesity due to BBS (<jats:italic>n<\/jats:italic>\u2009=\u200911) or biallelic variants in <jats:italic>LEPR<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20094) or <jats:italic>POMC<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20092) who either started setmelanotide in routine care between 2022 and 2024 or continued therapy after participating in the RM\u2010493\u2010022 clinical trial. The average follow\u2010up time was 14.4\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients experienced a clinically significant weight reduction of 20% from their highest pre\u2010treatment weight within the first year. Those previously treated in a clinical trial maintained their weight loss over time. Additionally, eating behavior improved, with significant reductions in hunger (\u221262%), food craving (\u221241%), and external eating evaluated by DEBQ. The overall safety profile was consistent with phase 3 trials data, without any new safety signals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings confirm the drug's long\u2010term clinical benefit and safety profile in a routine\u2010care setting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.70002","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T01:44:21Z","timestamp":1756863861000},"page":"1865-1872","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Real\u2010World Efficacy and Safety of Setmelanotide in Adults With Monogenic or Syndromic Obesity: A Prospective Cohort Study"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1821-953X","authenticated-orcid":false,"given":"Francois","family":"Mifsud","sequence":"first","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, Service de 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