{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:40Z","timestamp":1792788340965,"version":"4.5.0"},"reference-count":30,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010571","name":"German Federal Ministry of Research and Education","doi-asserted-by":"publisher","award":["01GM2203E"],"award-info":[{"award-number":["01GM2203E"]}],"id":[{"id":"10.13039\/501100010571","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rhythm Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objective<\/jats:title>\n                    <jats:p>The melanocortin-4 receptor agonist setmelanotide compensates for upstream gene defects in the brain leptin-melanocortin pathway and reduces hyperphagia and obesity in selected monogenic obesity forms and Bardet-Biedl syndrome (BBS). We aimed to evaluate the short-term impact of setmelanotide treatment in BBS presenting original real-world data focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and\/or hyperphagia and planned setmelanotide therapy. Ultrasound examination of the liver including shear wave elastography, dispersion and attenuation imaging (ATI), a bioimpedance analysis, and a hyperphagia questionnaire survey were applied in addition to clinical data collection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-six patients with BBS (mean age 19.2 years, range [6.2; 51.8]; mean body mass index (BMI) z-score 2.95, range [1.32; 4.84]) were included. All were classified with MASLD (54% S3, 23% each S1 and S2). After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1\u2005mL\/min\/1.73\u2005m\u00b2 (95% confidence interval (CI) [4.3; 15.9]). The following parameters also improved: BMI z-score \u22120.5 (95% CI [\u22120.6; \u22120.3]); hyperphagia score \u221212.3 (95% CI [\u221215.5; \u22129.0]); total body fat \u22123.1% (95% CI [\u22125.7; \u22120.5]); ATI \u22120.14\u2005dB\/cm\/MHZ (95% CI [\u22120.17; \u22120.11]). A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1. MASLD improvement correlated only with liver size, not BMI reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Setmelanotide treatment is associated with improvement of MASLD independent of BMI reduction as well as increased glomerular filtration rate in BBS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf483","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T11:25:32Z","timestamp":1756725932000},"page":"721-733","source":"Crossref","is-referenced-by-count":9,"title":["Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4389-0903","authenticated-orcid":false,"given":"Tom","family":"H\u00fchne","sequence":"first","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna Maria","family":"Polichronidou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilja","family":"Finkelberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7965-8888","authenticated-orcid":false,"given":"Pia","family":"Brensing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Jaegers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5617-4451","authenticated-orcid":false,"given":"Lars","family":"Dinkelbach","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Kiewert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Galetzka","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8144-5428","authenticated-orcid":false,"given":"Eva-Maria","family":"Huessler","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4980-706X","authenticated-orcid":false,"given":"Thomas","family":"Scherer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-2252","authenticated-orcid":false,"given":"Arend","family":"B\u00f6kenkamp","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam University Medical Centers , Amsterdam 1105 ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3630-4386","authenticated-orcid":false,"given":"Anja","family":"G\u00e4ckler","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-6418","authenticated-orcid":false,"given":"Lars","family":"Pape","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-9204","authenticated-orcid":false,"given":"Metin","family":"Cetiner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen , Essen 45147 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"issue":"2","key":"2026021918531358600_dgaf483-B1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.molmed.2018.12.002","article-title":"Melanocortin-4 receptor signalling: importance for weight regulation and obesity treatment","volume":"25","author":"K\u00fchnen","year":"2019","journal-title":"Trends Mol Med"},{"issue":"12","key":"2026021918531358600_dgaf483-B2","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S2213-8587(22)00277-7","article-title":"Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstr\u00f6m syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period","volume":"10","author":"Haqq","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"5","key":"2026021918531358600_dgaf483-B3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1055\/a-2251-5382","article-title":"Verbesserte Versorgungs-und Behandlungsoptionen f\u00fcr Patienten mit Hyperphagie-assoziierter Adipositas bei Bardet-Biedl-Syndrom [Improved care and treatment options for patients with hyperphagia-associated obesity in Bardet-Biedl Syndrome]","volume":"236","author":"Cetiner","year":"2024","journal-title":"Klin Padiatr"},{"issue":"11","key":"2026021918531358600_dgaf483-B4","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/s41431-024-01634-7","article-title":"Bardet-Biedl syndrome improved diagnosis criteria and management: inter European reference networks consensus statement and recommendations","volume":"32","author":"Dollfus","year":"2024","journal-title":"Eur J Hum Genet"},{"issue":"2","key":"2026021918531358600_dgaf483-B5","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/hep.30254","article-title":"Burden of illness and economic model for patients with nonalcoholic steatohepatitis in the United States","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"issue":"1","key":"2026021918531358600_dgaf483-B6","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s13023-024-03400-w","article-title":"Ultrasound evaluation of kidney and liver involvement in Bardet\u2013Biedl syndrome","volume":"19","author":"Cetiner","year":"2024","journal-title":"Orphanet J Rare Dis"},{"issue":"4","key":"2026021918531358600_dgaf483-B7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ajmg.c.30225","article-title":"Liver and kidney disease in ciliopathies","volume":"151C","author":"Gunay-Aygun","year":"2009","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2026021918531358600_dgaf483-B8","unstructured":"H\u00fchne T, Polichronidou IM, Finkelberg I, et al \u00a0Supplementary data related to the orignal article \u201cImpact of the melanocortin-4 receptor agonist setmelanotide on MASLD and kidney function in Bardet-Biedl syndrome\u201d by H\u00fchne et al. figshare. Datase. 2025. 10.6084\/m9.figshare.29918543.v2."},{"issue":"8","key":"2026021918531358600_dgaf483-B9","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s001120170107","article-title":"Perzentile f\u00fcr den Body-mass-Index f\u00fcr das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben","volume":"149","author":"Kromeyer-Hauschild","year":"2001","journal-title":"Monatsschr Kinderheilkd"},{"issue":"6","key":"2026021918531358600_dgaf483-B10","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1080\/03014460.2020.1808065","article-title":"A method for calculating BMI z-scores and percentiles above the 95th percentile of the CDC growth charts","volume":"47","author":"Wei","year":"2020","journal-title":"Ann Hum Biol"},{"issue":"7","key":"2026021918531358600_dgaf483-B11","doi-asserted-by":"crossref","first-page":"e13915","DOI":"10.1111\/obr.13915","article-title":"Hyperphagia in Bardet-Biedl syndrome: pathophysiology, burden, and management","volume":"26","author":"Beales","year":"2025","journal-title":"Obes Rev"},{"issue":"9","key":"2026021918531358600_dgaf483-B12","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/ckj\/sfad039","article-title":"New and old GFR equations: a European perspective","volume":"16","author":"Delanaye","year":"2023","journal-title":"Clin Kidney J"},{"issue":"2","key":"2026021918531358600_dgaf483-B13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1053\/j.ajkd.2021.10.013","article-title":"Self-reported race, serum creatinine, cystatin C, and GFR in children and young adults with pediatric kidney diseases: a report from the Chronic Kidney Disease in children (CKiD) study","volume":"80","author":"Ng","year":"2022","journal-title":"Am J Kidney Dis"},{"issue":"3","key":"2026021918531358600_dgaf483-B14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/10408363.2018.1427041","article-title":"Endogenous markers for kidney function in children: a review","volume":"55","author":"den Bakker","year":"2018","journal-title":"Crit Rev Clin Lab Sci"},{"issue":"11","key":"2026021918531358600_dgaf483-B15","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.clnu.2022.09.008","article-title":"Influence of the type of electrodes in the assessment of body composition by bioelectrical impedance analysis in the supine position","volume":"41","author":"Supertuis","year":"2022","journal-title":"Clin Nutr"},{"key":"2026021918531358600_dgaf483-B16","doi-asserted-by":"crossref","first-page":"1020690","DOI":"10.3389\/fped.2023.1020690","article-title":"Validation of attenuation imaging coefficient, shear wave elastography, and dispersion as emerging tools for non-invasive evaluation of liver tissue in children","volume":"11","author":"Cetiner","year":"2023","journal-title":"Front Pediatr"},{"issue":"3","key":"2026021918531358600_dgaf483-B17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2214\/AJR.19.21796","article-title":"Liver shear wave speed and other quantitative ultrasound measures of liver parenchyma: prospective evaluation in healthy children and adults","volume":"214","author":"Trout","year":"2020","journal-title":"AJR Am J Roentgenol"},{"issue":"12","key":"2026021918531358600_dgaf483-B18","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1007\/s00330-019-06272-y","article-title":"Assessment of hepatic steatosis by using attenuation imaging: a quantitative, easy-to-perform ultrasound technique","volume":"29","author":"Bae","year":"2019","journal-title":"Eur Radiol"},{"issue":"1","key":"2026021918531358600_dgaf483-B19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J Stat Softw"},{"issue":"31","key":"2026021918531358600_dgaf483-B20","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A single-cell type transcriptomics map of human tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci Adv"},{"issue":"1","key":"2026021918531358600_dgaf483-B21","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1038\/s41467-019-10684-1","article-title":"Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis","volume":"10","author":"Hackl","year":"2019","journal-title":"Nat Commun"},{"issue":"11","key":"2026021918531358600_dgaf483-B22","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1016\/j.cmet.2022.09.020","article-title":"Leptin increases hepatic triglyceride export via a vagal mechanism in humans","volume":"34","author":"Metz","year":"2022","journal-title":"Cell Metab"},{"issue":"7","key":"2026021918531358600_dgaf483-B23","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.medj.2021.04.001","article-title":"Metreleptin therapy for nonalcoholic steatohepatitis: open-label therapy interventions in two different clinical settings","volume":"2","author":"Akinci","year":"2021","journal-title":"Med"},{"issue":"6","key":"2026021918531358600_dgaf483-B24","doi-asserted-by":"crossref","first-page":"E711","DOI":"10.1152\/ajpendo.00174.2023","article-title":"Metabolic consequences of skeletal muscle- and liver-specific BBSome deficiency","volume":"325","author":"Rouabhi","year":"2023","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"3","key":"2026021918531358600_dgaf483-B25","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/jcsm.13469","article-title":"Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer","volume":"15","author":"Hanna","year":"2024","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"14","key":"2026021918531358600_dgaf483-B26","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.1523\/JNEUROSCI.23-14-05998.2003","article-title":"Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin","volume":"23","author":"Rahmouni","year":"2003","journal-title":"J Neurosci"},{"key":"2026021918531358600_dgaf483-B27","doi-asserted-by":"crossref","first-page":"1440250","DOI":"10.3389\/fendo.2024.1440250","article-title":"Obesity-related renal dysfunction: gender-specific influence of visceral adiposity and early impact of metabolic and bariatric surgery","volume":"15","author":"Popa","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026021918531358600_dgaf483-B28","doi-asserted-by":"crossref","first-page":"651236","DOI":"10.3389\/fphys.2021.651236","article-title":"Melanocortin system in kidney homeostasis and disease: novel therapeutic opportunities","volume":"12","author":"Chang","year":"2021","journal-title":"Front Physiol"},{"issue":"11","key":"2026021918531358600_dgaf483-B29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/S2213-8587(22)00243-1","article-title":"Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial","volume":"10","author":"Heerspink","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"5","key":"2026021918531358600_dgaf483-B30","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00125-023-05876-w","article-title":"Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial","volume":"66","author":"Gullaksen","year":"2023","journal-title":"Diabetologia"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf483\/64202898\/dgaf483.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/3\/721\/64202898\/dgaf483.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/111\/3\/721\/64202898\/dgaf483.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T23:53:23Z","timestamp":1771545203000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/111\/3\/721\/8247337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9,4]]},"published-print":{"date-parts":[[2026,2,20]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf483","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,9,4]]}}}