HomePeptides › Setmelanotide

Setmelanotide

Imcivree, RM-493

Tier 1 · FDA Approved
Class
MC4R agonist
Molecular target
MC4R
Sequence / structure
Cyclic 8-aa peptide
Evidence tier
Tier 1 — FDA Approved
Category
Melanocortin

Biology & mechanism

A selective MC4R agonist, and a genuine piece of precision medicine. The leptin-melanocortin pathway regulates hunger; when it is broken upstream by a genetic defect — POMC, PCSK1 or LEPR deficiency — hunger signalling runs unopposed. Setmelanotide restores signalling downstream of the defect by agonising MC4R directly, bypassing the broken component. It works because the specific lesion is known, which is exactly why it does not work as a general obesity drug.

What the research actually shows

Phase 3 trials in genetically defined obesity syndromes demonstrated substantial weight reduction and, notably, reduction in hunger. Later trials supported expansion to acquired hypothalamic obesity.

Regulatory status

FDA-approved as Imcivree, for patients aged 2 and older with obesity due to Bardet-Biedl syndrome or genetically confirmed POMC, PCSK1 or LEPR deficiency; and, following expansion, for acquired hypothalamic obesity in patients aged 4 and older. Prescription-only. Requires genetic confirmation — the approval is tied to the genotype, not to obesity generally.

Safety signals

Skin hyperpigmentation is expected and mechanism-based. Injection-site reactions, nausea. Spontaneous penile erections and sexual adverse events are labelled. Depression and suicidal ideation are labelled and require monitoring. Full ophthalmological and skin examination required before and during treatment.

No usage guidance is published here

Forge Bioenergy does not publish dosing, reconstitution, or administration protocols for any peptide. See our editorial policy for why. If you are considering any substance on this page, that conversation belongs with a licensed physician.

References & further reading

Regulatory status changes. This page reflects our reading of public sources as of July 2026 and should be independently verified before it is relied upon.

Important notice Forge Bioenergy publishes scientific reference information only. Nothing on this site is medical advice, a therapeutic claim, or a recommendation to use any substance in humans. Many peptides described here are not approved by the FDA for any use, and several are approved only for narrow indications under prescription. We do not publish dosing, administration, or usage protocols. Consult a licensed physician before making any medical decision.