Every peptide, mapped to the body.

153 peptides, from approved drugs to compounds still in trials, sorted by where they act.

FDA-approved
In clinical trials
Wellness and performance
Cosmetic and topical

Loading the body

FDA-approved

Digestive & weight

Setmelanotide

EvidenceFDA approved

ClassMC4R agonist

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.

Reviewed by: William Maish, MD MBA MPH, Clinical Product Lead
Published: October 5, 2026
Last updated: October 5, 2026

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

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 loss¹ 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?

Yes. Setmelanotide was approved² 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

More for digestive & weight

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)30364-8¹), indexed on PubMed. This document is educational and does not constitute medical advice.