Setmelanotide
An FDA-approved MC4R agonist for rare genetic obesity disorders, representing a precision medicine approach to weight management.
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This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician
What is Setmelanotide?
Setmelanotide is a cyclic peptide that activates the melanocortin-4 receptor (MC4R), a key regulator of appetite and energy balance. It is FDA-approved for chronic weight management in patients with specific rare genetic obesity conditions (POMC, PCSK1, or LEPR deficiency). It represents one of the first precision medicine approaches to obesity treatment.
Why People Talk About It
Treatment of rare genetic obesity (POMC/LEPR deficiency)
StrongPrecision medicine approach to weight management
StrongMC4R pathway modulation for appetite control
ModerateHow It Works
In certain rare genetic conditions, the brain's appetite-control pathway is broken. Setmelanotide restores the missing signal by directly activating the MC4 receptor, which tells the brain 'you're full' — something these patients' bodies cannot do on their own.
Common Questions
Safety Information
Common Side Effects
Cautions
- • Only for genetically confirmed obesity
- • Risk of depression and suicidal ideation
- • Skin darkening is expected
- • Sexual adverse effects common
What We Don't Know
Long-term effects of chronic MC4R activation are still being studied.
Published Research
30 studiesEfficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis
Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome
Could setmelanotide be the game-changer for acquired hypothalamic obesity?
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
RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals
Setmelanotide in Bardet-Biedl Syndrome: A 52-Week Comparison of Phase 3 Trial Participants With a Matched Registry Cohort
Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial
Monoallelic pathogenic variants in LEPR do not cause obesity
Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results
Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency
Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial
A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist
Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials
Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency
Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome
Setmelanotide: A Melanocortin-4 Receptor Agonist for the Treatment of Severe Obesity Due to Hypothalamic Dysfunction
Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity
Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity
Setmelanotide: First Approval
Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice?
Setmelanotide (Imcivree) for rare genetic forms of obesity
Setmelanotide
Case Report: Improvement in cognitive functioning following setmelanotide initiation in a patient with Bardet-Biedl syndrome
Resolution of chronic idiopathic urticaria with setmelanotide in a patient with Bardet-Biedl Syndrome: A case report
Clinically Meaningful Outcomes after 1 Year of Treatment with Setmelanotide in an Adult Patient with a Variant in SH2B1
Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers
Setmelanotide
SAR investigation and synergistic optimization of setmelanotide yields a potent, selective, and soluble MC4R agonist
Always consult a qualified clinician
This information is for educational purposes. Peptide therapy should be guided by a licensed healthcare provider. Connect with a Noho clinician
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Quick Facts
- Class
- Melanocortin-4 Receptor Agonist
- Evidence
- Strong
- Safety
- Well-Studied
- Updated
- Mar 2026
- Citations
- 30PubMed
Also known as
Tags
Related Goals
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.
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