Digestive & weight MC4R agonist
Setmelanotide
Regulatory status
Status at a glance
503A compounding status
Not nominated
We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.
- Also known as
- Imcivree
- FDA approval
- An FDA-approved product contains this peptide
- 503B outsourcing
- Not determined
- Anti-doping (WADA)
- Not on the WADA Prohibited List
- DEA schedule
- Not a controlled substance
About peptide status
Most peptides discussed here are not FDA-approved for any use, and products labeled “research use only” are not for human use. Removal from Category 2 does not authorize compounding. PCAC votes are non-binding recommendations; FDA and HHS make the final decisions.
This is not medical or legal advice, and we do not publish dosing, sourcing or reconstitution information. Talk with a licensed clinician before using any peptide.
If you think you are having a medical emergency, call 911.
Key takeaway
Setmelanotide (sold as Imcivree) is a peptide that switches on the brain's melanocortin-4 receptor to reduce hunger and body weight in people with certain rare genetic forms of obesity or with acquired hypothalamic obesity. It restores a signal in the appetite pathway that is broken by certain inherited gene defects or by damage to the hypothalamus. It has been FDA-approved in the U.S. since 2020 and is given as a daily subcutaneous injection.
At a glance
- What it is
- A melanocortin-4 receptor (MC4R) agonist peptide
- Approved for
- Obesity due to POMC, PCSK1, or LEPR deficiency, obesity from Bardet-Biedl syndrome, and acquired hypothalamic obesity
- Key fact
- In pivotal trials, most patients with POMC deficiency and a substantial share with LEPR deficiency lost at least 10 percent of body weight
- Route
- Subcutaneous injection, once daily
- Evidence strength
- FDA approved
Summary
Setmelanotide, sold as Imcivree, is an FDA-approved peptide for certain rare genetic obesity. Learn how it works, who it is for, and its side effects.
What is setmelanotide?
Setmelanotide, sold under the brand Imcivree, is a peptide that activates the melanocortin-4 receptor (MC4R), a key control point in the brain's regulation of appetite and body weight. It is used for rare genetic forms of obesity in which the signaling pathway leading to MC4R is disrupted, causing relentless hunger from early childhood, and for acquired hypothalamic obesity, which follows damage to the hypothalamus. It was developed under the codes RM-493 and BIM-22493 and approved in the United States in 2020.
How does setmelanotide work?
Setmelanotide is a selective agonist of the MC4R, a receptor in the hypothalamus that normally suppresses hunger when stimulated. In the leptin-melanocortin pathway, signals from fat stores pass through several genes, including POMC, PCSK1, and LEPR, before reaching MC4R. When one of those upstream genes is defective, MC4R is not adequately stimulated, and the person experiences severe, persistent hunger and early-onset obesity. Setmelanotide bypasses the broken upstream step by stimulating MC4R directly, reducing hunger and body weight.
For the genetic forms, it is used only when the condition is genetically confirmed. In the pivotal trials, about 80 percent of patients with POMC deficiency and roughly 45 percent with LEPR deficiency achieved at least 10 percent weight loss over about a year, with reductions in hunger scores. A notable, expected effect is skin darkening, because MC4R's cousin receptor MC1R, which controls pigment, is also mildly stimulated.
Is it FDA-approved?
Editor’s note
Status: Yes. Setmelanotide was approved by the FDA for chronic weight management, with indications added in stages. Indication | FDA approval | Approved ages Obesity due to confirmed POMC, PCSK1, or LEPR deficiency | 2020 | 2 years and older, lowered since first approval Obesity due to Bardet-Biedl syndrome | 2022 | 2 years and older, lowered since first approval Acquired hypothalamic obesity | March 2026 | Adults and children 4 and older
Category: FDA-approved · Primary body area: Digestive & weight
Yes. Setmelanotide was approved by the FDA for chronic weight management, with indications added in stages.
| Indication | FDA approval | Approved ages |
|---|---|---|
| Obesity due to confirmed POMC, PCSK1, or LEPR deficiency | 2020 | 2 years and older, lowered since first approval |
| Obesity due to Bardet-Biedl syndrome | 2022 | 2 years and older, lowered since first approval |
| Acquired hypothalamic obesity | March 2026 | Adults and children 4 and older |
What is setmelanotide prescribed for?
Setmelanotide is prescribed to reduce excess body weight and keep it off in people with genetically confirmed POMC, PCSK1, or LEPR deficiency, Bardet-Biedl syndrome, or acquired hypothalamic obesity. It is not approved for common obesity.
What are the side effects?
According to the prescribing information, common side effects include:
- Darkening of the skin and moles (hyperpigmentation), prompting skin checks
- Injection-site reactions
- Nausea, vomiting, diarrhea, and abdominal pain
- Headache
- Depression
- Spontaneous erections in males
More serious considerations include:
- Depression and suicidal thoughts, which warrant monitoring
- Disturbances of sexual arousal, including sexual adverse reactions in females
- Serious allergic reactions
- In acquired hypothalamic obesity, acute adrenal insufficiency and sodium imbalance
- Caution with the benzyl alcohol preservative in newborns and low-birth-weight infants
Sources: FDA prescribing information for Imcivree; the phase 3 POMC and LEPR trials (Clément et al., The Lancet Diabetes & Endocrinology, 2020, DOI: 10.1016/S2213-8587(20)30364-8), indexed on PubMed. This document is educational and does not constitute medical advice.
Registered human trials
0 registered human trials on ClinicalTrials.gov that we reviewed
Sources
- [1]
- [2]
approved (PDF)
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