Setmelanotide (Imcivree)
Weight Management Peptidefda_approvedAlso known as: Imcivree, BMS-470539, RM-493
FDA-approved melanocortin-4 receptor (MC4R) agonist for rare genetic obesity disorders. Targets the brain's hunger signaling pathway to reduce appetite and increase energy expenditure.
Overview
Setmelanotide is a groundbreaking FDA-approved peptide that activates melanocortin-4 receptors (MC4R) in the hypothalamus — the brain's appetite control center. It was developed specifically for patients with rare genetic mutations that disrupt the melanocortin pathway (POMC, PCSK1, LEPR deficiency), causing severe early-onset obesity. By restoring signaling in this critical hunger pathway, setmelanotide can produce dramatic weight loss in these patients, often 25%+ of body weight. It represents a triumph of precision medicine — targeting the specific molecular defect causing the disease.
Mechanism of Action
Setmelanotide activates the MC4R pathway: (1) Agonizes melanocortin-4 receptors in the hypothalamus; (2) Restores downstream signaling in the leptin-melanocortin pathway; (3) Reduces hunger and food intake through central satiety signaling; (4) Increases energy expenditure and metabolic rate; (5) Specifically effective when upstream mutations (POMC, LEPR, PCSK1) prevent natural MC4R activation; (6) Does not work through GLP-1 mechanisms — entirely distinct pathway from semaglutide/tirzepatide.
Molecular Formula
C112H152ClN26O18S2
Molecular Weight
2237.2 g/mol
Sequence
Cyclic peptide: Ac-Arg-Cys(1)-D-Ala-His-D-Phe-Arg-Trp-Cys(1)-NH2
Dosage Protocols
Dose Range
1mg – 3mg
Frequency
Once daily
Route
subcutaneous injection
Cycle Length
Ongoing
Start at 2mg daily for adults. Titrate to 3mg if insufficient response after 2 weeks. Available via REMS program only.
Source: FDA prescribing information
🧮 Personalized Dosage Calculator
💰 Estimated Pricing
Typical Supply
10mg/mL multi-dose vial
Last Updated
2026-02
Brand name Imcivree. REMS program. Specialty pharmacy only.
⚠️ Prices are estimates based on publicly available data and may vary significantly by vendor, location, and prescription status. This is not medical or financial advice.
Side Effects
| Effect | Severity |
|---|---|
| mild | |
| mild | |
| mild | |
| mild | |
| severe |
Pros & Cons
First precision medicine for genetic obesity
Can produce 25%+ weight loss in responsive patients
FDA-approved with REMS safety monitoring
Novel mechanism distinct from GLP-1 drugs
Life-changing for patients with rare genetic conditions
Proven efficacy in clinical trials
Only approved for rare genetic obesity (genetic testing required)
Boxed warning for depression/suicidal ideation
Causes skin darkening in most patients
Daily injections required
Very expensive without insurance
Not approved for general obesity
Research Studies
🩸 Blood Work
No specific bloodwork requirements reported for this peptide. General health panels are always recommended before starting any peptide protocol.
Legal Status
FDA-approved (2020) for chronic weight management in patients 6+ years with POMC, PCSK1, or LEPR deficiency obesity confirmed by genetic testing.
Readers Also Viewed
Semaglutide
99An FDA-approved GLP-1 receptor agonist used for type 2 diabetes and chronic weight management, producing significant weight loss of 15-17% body weight in clinical trials.
BPC-157
98A 15-amino acid synthetic peptide derived from human gastric juice that promotes healing of tendons, ligaments, muscles, gut lining, and other tissues through multiple regenerative pathways.
Tirzepatide
97A first-in-class dual GIP/GLP-1 receptor agonist that produces up to 22.5% body weight loss, approved for type 2 diabetes and obesity management.
CJC-1295 + Ipamorelin (Combo)
95The most popular growth hormone peptide combination, pairing a GHRH analog (CJC-1295) with a ghrelin mimetic (Ipamorelin) for synergistic GH release with minimal side effects.
Related Peptides
Semaglutide
An FDA-approved GLP-1 receptor agonist used for type 2 diabetes and chronic weight management, producing significant weight loss of 15-17% body weight in clinical trials.
Tirzepatide
A first-in-class dual GIP/GLP-1 receptor agonist that produces up to 22.5% body weight loss, approved for type 2 diabetes and obesity management.
CJC-1295 + Ipamorelin (Combo)
The most popular growth hormone peptide combination, pairing a GHRH analog (CJC-1295) with a ghrelin mimetic (Ipamorelin) for synergistic GH release with minimal side effects.
Ipamorelin
A highly selective growth hormone-releasing peptide (GHRP) that stimulates GH release with minimal impact on cortisol, prolactin, or appetite, making it the cleanest GHRP available.