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Last reviewed: March 2026Sources: PubMed, FDA, WADA Prohibited List

Evidence graded using the PeptideScholar A-D system

Setmelanotide

AFDA Approved
70
Good Credibility
2 cited studyies · Evidence level A

Melanocortin-4 receptor (MC4R) agonist · 8 amino acids · Brand: Imcivree

FDA ApprovedPrescription Required

Setmelanotide is the first melanocortin-4 receptor (MC4R) agonist approved by the FDA for chronic weight management in patients with rare genetic obesity syndromes (POMC, PCSK1, or LEPR deficiency, or Bardet-Biedl syndrome). It is the first obesity drug that targets the hypothalamic melanocortin pathway rather than the gut-brain axis.

Mechanism of Action

Activates MC4R receptors in the hypothalamus, restoring satiety signaling and energy expenditure in patients with genetic defects upstream of MC4R (POMC, LEPR, PCSK1, BBS). MC4R is the final common pathway for leptin-melanocortin satiety signaling; setmelanotide bypasses upstream defects.

Benefits

  • First and only approved therapy for genetic MC4R-pathway obesity[1][2]
  • Dramatic weight loss (~25% body weight) in POMC/LEPR deficiency[1]
  • Reduces hunger and restores satiety signaling
  • Improves quality of life and reduces comorbidities in rare obesity[2]
Not Medical Advice — Research-Reported Information Only

This content is for informational purposes only and does not constitute medical advice.

Setmelanotide — Dosing in Published Research

Reported Routes: Subcutaneous injection
2 mg SC daily initially; titrate to 3 mg daily after 2 weeks based on tolerability and response. Must have confirmed genetic diagnosis of POMC, PCSK1, LEPR deficiency, or BBS prior to initiation. Monitor for skin pigmentation changes and mood disorders.

The dosing information above is sourced from published research literature and clinical trials. These are not recommendations. Individual responses vary. Always consult a healthcare provider before considering any peptide-based therapy.

Side Effects

  • Injection site reactions (erythema, pruritus)
  • Hyperpigmentation (skin darkening, including nevi)
  • Nausea, vomiting, diarrhea
  • Spontaneous penile erection in males
  • Depression and suicidal ideation (boxed warning)

Ready to Discuss Setmelanotide with a Doctor?

Setmelanotide is FDA-approved and available by prescription. Licensed telehealth providers can evaluate if it's right for you.

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FDA ApprovedBoard-Certified DoctorsPrescription if Appropriate

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Approved Treatment Routing

Setmelanotide in PeptideScholar's current approved-treatment dataset

Setmelanotide is currently modeled on this site as an approved treatment path for: Chronic weight management in adult and pediatric patients aged 6 years and older with obesity due to POMC, PCSK1, or LEPR deficiency, or Bardet-Biedl syndrome. Brand names in the current dataset: Imcivree.

Validation Note
This block reflects the site's current structured treatment data and internal routing logic. It is not a substitute for checking current prescribing, labeling, payer, or local regulatory details.
View treatment routing profilesUse provider matcherReview legal guidance

Research & Evidence

Case SeriesN Engl J Med, 2016

Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist.

Setmelanotide produced substantial weight loss (~25% body weight) and dramatic hunger reduction in two patients with POMC deficiency, establishing proof-of-concept for MC4R agonism in genetic obesity

PMID: 27468060
RCTLancet Diabetes Endocrinol, 2025

Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.

Setmelanotide produced significant BMI reduction in children aged 2-5 years with MC4R-pathway genetic obesity, with a safety profile consistent with adult data

PMID: 39549719

References

  1. 1. Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist.. N Engl J Med, 2016. “Setmelanotide produced substantial weight loss (~25% body weight) and dramatic hunger reduction in two patients with POMC deficiency, establishing proof-of-concept for MC4R agonism in genetic obesity” [PMID: 27468060]
  2. 2. Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.. Lancet Diabetes Endocrinol, 2025. “Setmelanotide produced significant BMI reduction in children aged 2-5 years with MC4R-pathway genetic obesity, with a safety profile consistent with adult data” [PMID: 39549719]

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Setmelanotide FAQ

Medical Disclaimer

This content is for informational and educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.

Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment. Do not disregard professional medical advice based on information found on this site.

No claims of therapeutic efficacy are made for substances that are not FDA-approved for the discussed indications. Research citations reflect published findings and do not imply endorsement.

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