ArticleObesity research & clinical practice
Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome.
Article in Obesity research & clinical practice. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hyperphagia in rare melanocortin-4 receptor pathway diseases: therapeutic options and assessing treatment response.Reviews in endocrine & metabolic disorders · 2025Pooled it
- Tirzepatide for weight and behavior management in a patient with Smith-Magenis syndrome.JCEM case reports · 2026Article
- Weight Loss Following Liraglutide Therapy in a Patient With Smith-Magenis Syndrome: A Case Report.Cureus · 2026Article
- Management of Childhood Obesity.International journal of molecular sciences · 2026Review
- Investigating food-related behaviors in Smith-Magenis syndrome: tailoring a questionnaire for a rare disease.Journal of rare diseases (Berlin, Germany) · 2026Article
- The effect of melanocortin-4 receptor agonist drugs on obesity and metabolic risk factors: a systematic review and meta-analysis.Diabetology & metabolic syndrome · 2025Review
- Weight Management in a Patient With Smith-Magenis Syndrome: The Role of GLP-1 Receptor Agonists.JCEM case reports · 2025Article
- Antiobesity Pharmacotherapy for Patients With Genetic Obesity Due to Defects in the Leptin-Melanocortin Pathway.Endocrine reviews · 2025Review
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Setmelanotide-mediated MC4R activation improves hypothalamic obesity via CaMKK2/AMPK pathways.Frontiers in pharmacology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundSmith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS.
methodsPeople with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety.
results12 individuals, ages 11-39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was - 0.28 % [(95 % CI, -2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death.
conclusionsIn this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.
Indexed as
Identifiers
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.