Trial reportMolecular metabolism2017
Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency.
Trial report in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07674290 (Real-World Effectiveness, Safety and Patient-reported Outcomes of Setmelanotide in Patients With Bardet-Biedl Syndrome), which is not on this map. Cited by 152 papers, 2 of them syntheses that pooled it.
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.
Real-World Effectiveness, Safety and Patient-reported Outcomes of Setmelanotide in Patients With Bardet-Biedl Syndrome: A Prospective Mono Centric Observational Interventional Study
Who cites it
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 290 citations in OpenAlex.
- Association of Mutations in theInternational journal of molecular sciences · 2026Pooled it
- Two Cases With an Early Presented Proopiomelanocortin Deficiency-A Long-Term Follow-Up and Systematic Literature Review.Frontiers in endocrinology · 2021Pooled it
- Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants.Frontiers in behavioral neuroscience · 2026Trial
- Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.Nature medicine · 2025Trial
- MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.Nature medicine · 2018Trial
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Inversed impaired osteogenic activity in children with severe obesity due to MC4R deficiency compared to LEP and LEPR deficiency.International journal of obesity (2005) · 2026Article
- Dual activation of MC3R and MC4R drives weight loss and reduces food intake in male primates with obesity.Nature communications · 2026Article
- Protein-truncating variants in APBA1 in minors with severe, early-onset obesity: implications for genetic testing.Molecular and cellular pediatrics · 2026Article
- Management of Childhood Obesity.International journal of molecular sciences · 2026Review
- Tirzepatide and Metformin Effects on Hunger and BMI in an Adolescent with Hyperphagia and Severe Obesity due to MC4R Deficiency: A Case Report.Obesity facts · 2026Article
- Review
- 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
- Single-nucleus atlas provides insights into changes in the evolution of the pig hippocampus.BMC biology · 2026Article
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Monogenic obesity due to MC4R deficiency: lessons from a multigenerational case.Molecular and cellular pediatrics · 2026Article
- The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives.Frontiers in endocrinology · 2026Review
- Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk.Nature medicine · 2025Article
92 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
28 authors at 6 institutions in 5 countries.
Funding
Abstract
objectivePro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency.
methodsWe studied the effects of Setmelanotide on mutant MC4Rs in cells and the weight loss response to Setmelanotide administration in rodent studies and a human clinical trial. We annotated the functional status of 369 published MC4R variants.
resultsIn cells, we showed that Setmelanotide is significantly more potent at MC4R than the endogenous ligand alpha-melanocyte stimulating hormone and can disproportionally rescue signaling by a subset of severely impaired MC4R mutants. Wild-type rodents appear more sensitive to Setmelanotide when compared to MC4R heterozygous deficient mice, while MC4R knockout mice fail to respond. In a 28-day Phase 1b clinical trial, Setmelanotide led to weight loss in obese MC4R variant carriers. Patients with POMC defects upstream of MC4R show significantly more weight loss with Setmelanotide than MC4R deficient patients or obese controls.
conclusionsSetmelanotide led to weight loss in obese people with MC4R deficiency; however, further studies are justified to establish whether Setmelanotide can elicit clinically meaningful weight loss in a subset of the MC4R deficient obese population.
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What OpenQuestion holds
Registered trials
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.