{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:28:55Z","timestamp":1792466935663,"version":"4.5.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022223","name":"Rhythm Pharmaceuticals, Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022223","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Bardet-Biedl syndrome (BBS) is a rare genetic disease associated with disruptions in melanocortin-4 receptor pathway signaling that can contribute to increased risk for metabolic syndrome and obesity-related comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Here, MetS-Z-BMI scores, a continuous measure based on body mass index (BMI), were calculated to determine metabolic syndrome severity and response to treatment with the melanocortin-4 receptor agonist setmelanotide in BBS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All patients from a phase 3 study (NCT03746522) of setmelanotide with data required for the calculation of MetS-Z-BMI scores were included. Mean MetS-Z-BMI score was determined at baseline and Week 52; subgroup analyses were conducted by sex, age, genotype, and response to setmelanotide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MetS-Z-BMI scores were evaluable for 22 of 32 patients enrolled. Baseline mean (SD) MetS-Z-BMI score across patients was 1.1 (0.5); baseline mean (SD) odds ratios of future cardiovascular disease or type 2 diabetes were 3.1 (1.5) and 3.7 (1.7), respectively, for adults and 10.2 (4.7) and 2.8 (1.3), respectively, for pediatric patients. Overall, mean (SD) MetS-Z-BMI score at Week 52 was reduced by 0.34 (0.62). Mean (SD) MetS-Z-BMI scores significantly differed depending on achievement of predetermined weight-based thresholds of \u226510% weight loss (patients aged \u226518 years) or \u22650.3-point reduction in BMI Z score (patients aged &amp;lt;18 years) at Week 52 (achievers, \u22120.64 [0.54]; nonachievers, 0.08 [0.47]; P = .0043). No significant difference was observed with other subgroup comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MetS-Z-BMI score reductions were observed after 52 weeks of treatment, suggesting that setmelanotide may decrease metabolic syndrome severity and risk of future obesity-related comorbidities in those with BBS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf079","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T15:22:49Z","timestamp":1738768969000},"page":"e3271-e3282","source":"Crossref","is-referenced-by-count":12,"title":["Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-4982","authenticated-orcid":false,"given":"Andrea M","family":"Haqq","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology, University of Alberta , Edmonton, AB ,","place":["Canada T6G 2B7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7769-6331","authenticated-orcid":false,"given":"Christine","family":"Poitou","sequence":"additional","affiliation":[{"name":"Nutrition Department, Reference Center of Rare Diseases PRADORT, Assistance Publique H\u00f4pitaux de Paris, Piti\u00e9-Salp\u00eatri\u00e8re Hospital , Paris 75013 ,","place":["France"]},{"name":"Sorbonne Universit\u00e9, Inserm, Nutrition and Obesities, Systemic Approaches NutriOmique Research Group , Paris 75013 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-5685","authenticated-orcid":false,"given":"Wendy K","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children's Hospital, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-8271","authenticated-orcid":false,"given":"Elizabeth","family":"Forsythe","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Guys and St. Thomas\u2019 Hospitals , London; National Bardet-Biedl Syndrome Clinics, Great Ormond Street Hospital, London WC1N 3BH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-9621","authenticated-orcid":false,"given":"Rushika","family":"Conroy","sequence":"additional","affiliation":[{"name":"Division of Weight Management, Division of Pediatric Endocrinology, Maine Medical Center , Portland, ME 04102 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2249-895X","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Dollfus","sequence":"additional","affiliation":[{"name":"CARGO and Department of Medical Genetics, H\u00f4pitaux Universitaires de Strasbourg, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace, Universit\u00e9 de Strasbourg , Strasbourg 67000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Rhythm Pharmaceuticals, Inc. , Boston, MA 02116 ,","place":["USA"]},{"name":"Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Touchot","sequence":"additional","affiliation":[{"name":"Rhythm Pharmaceuticals, Inc. , Boston, MA 02116 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzoma","family":"Okorie","sequence":"additional","affiliation":[{"name":"Marshfield Clinic Research Institute , Marshfield, WI 54449 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Beales","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Programme, University College London Great Ormond Street Institute of Child Health , London WC1N 1EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-6785","authenticated-orcid":false,"given":"Karine","family":"Cl\u00e9ment","sequence":"additional","affiliation":[{"name":"Nutrition Department, Reference Center of Rare Diseases PRADORT, Assistance Publique H\u00f4pitaux de Paris, Piti\u00e9-Salp\u00eatri\u00e8re Hospital , Paris 75013 ,","place":["France"]},{"name":"Sorbonne Universit\u00e9, Inserm, Nutrition and Obesities, Systemic Approaches NutriOmique Research Group , Paris 75013 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-0276","authenticated-orcid":false,"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Endocrinology, Universidad Aut\u00f3noma de Madrid, University Hospital Ni\u00f1o Jes\u00fas , Madrid 28009 ,","place":["Spain"]},{"name":"CIBER \u201cFisiopatolog\u00eda de la obesidad y nutrici\u00f3n\u201d (CIBEROBN), Instituto de Salud Carlos III , Madrid 28029 ,","place":["Spain"]},{"name":"IMDEA Food Institute , Madrid 28049 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"issue":"4","key":"2025091917033421100_dgaf079-B1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/cge.12373","article-title":"Genetic predictors of 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