Trial reportNature medicine2018
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.
Abstract readClinical Trial, Phase II
In one paragraph
Trial report in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.
0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed
15.4field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
170 citing papers in PubMed, 300 citations in OpenAlex.
- Monoallelic pathogenic variants in LEPR do not cause obesity.American journal of human genetics · 2024Trial
- Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.The lancet. Diabetes & endocrinology · 2022Trial
- Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder.The Journal of clinical investigation · 2022Trial
- Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency.Orphanet journal of rare diseases · 2022Trial
- The Impact of Long-term Physical Inactivity on Adipose Tissue Immunometabolism.The Journal of clinical endocrinology and metabolism · 2022Trial
- IMPROVE 2025: The 3rd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2026Article
- Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.Journal of the Endocrine Society · 2026Article
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.International journal of molecular sciences · 2026Article
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Steroid receptor coactivators: from basic research to translational opportunities.Endocrine reviews · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- Supply and Demand in the Mathematics of Rare Disease Drug Development: Why Choosing the Right Model Is Crucial.Clinical and translational science · 2026Review
- Management of Childhood Obesity.International journal of molecular sciences · 2026Review
- Melanocortin 3 Receptors Do Not Specifically Localize to Primary Cilia in Cultured Human and Rodent Neurons.Cell biochemistry and function · 2026Article
- The genetics of obesity: aetiology, prevention and therapy.Nature metabolism · 2026Review
- Melanocortin receptor 4 agonist setmelanotide treats opioid-induced respiratory depression.bioRxiv : the preprint server for biology · 2026Article
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
110 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 4 countries.
Karine Clément *Sorbonne Université, INSERM, NutriOmics team, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
Heike Biebermann *Institute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
I Sadaf Farooqi *University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Lex Van der Ploeg *Rhythm Pharmaceuticals, Boston, MA, USA.
Barbara WoltersInstitute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Christine PoitouSorbonne Université, INSERM, NutriOmics team, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
Lia PuderInstitute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Fred FiedorekRhythm Pharmaceuticals, Boston, MA, USA.
Keith GottesdienerRhythm Pharmaceuticals, Boston, MA, USA.
Gunnar KleinauInstitute of Medical Physics and Biophysics, Group Protein X-ray Crystallography and Signal Transduction, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Nicolas HeyderInstitute of Medical Physics and Biophysics, Group Protein X-ray Crystallography and Signal Transduction, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-8755-5433
Patrick ScheererInstitute of Medical Physics and Biophysics, Group Protein X-ray Crystallography and Signal Transduction, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Ulrike Blume-PeytaviDepartment of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Irina JahnkeDepartment of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Shubh SharmaRhythm Pharmaceuticals, Boston, MA, USA.
Jacek MokrosinskiUniversity of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Susanna WiegandCenter for Chronic Sick Children, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Anne MüllerInstitute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Katja WeißDepartment of Pediatric Cardiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Knut MaiDZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
Joachim SprangerDZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-8900-4467
Annette GrütersDepartment of Pediatric Endocrinology and Diabetes, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Oliver BlankensteinInstitute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Heiko KrudeInstitute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Peter KühnenInstitute for Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. peter.kuehnen@charite.de.
Humboldt-Universität zu Berlin · DEJazz Pharmaceuticals (United States) · USInserm · FRUniversity of Cambridge · GB
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic defects underlying the melanocortin-4 receptor (MC4R) signaling pathway lead to severe obesity. Three severely obese LEPR-deficient individuals were administered the MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia and body weight over an observation period of 45-61 weeks. Compared to formerly developed and tested MC4R agonists, setmelanotide has the unique capability of activating nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling pathway for selected MC4R variants. Our data demonstrate the potency of setmelanotide in treatment of individuals with diverse MC4R-related pathway deficiencies.
Indexed as
Weight LossAdolescentalpha-MSHEnzyme ActivationHEK293 CellsHumansMalePeptidesReceptor, Melanocortin, Type 4Receptors, LeptinType C PhospholipasesYoung Adultalpha-MSHLY2112688PeptidesReceptor, Melanocortin, Type 4Receptors, LeptinsetmelanotideType C Phospholipases
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.