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FDA approved for specific usesStrong human evidence for approved uses

Plain-English fact sheet

Setmelanotide

Also known as Imcivree, RM-493

Weight managementMetabolic healthRare and genetic conditions

Setmelanotide is a precision medicine for certain genetically or clinically defined obesity syndromes, not a treatment for common obesity.

Quick answer

Setmelanotide is FDA approved as Imcivree for long-term weight reduction in people age 2 and older with obesity caused by specified POMC, PCSK1, or LEPR deficiencies or Bardet-Biedl syndrome. It is not approved for general obesity.

By the PeptideFactSheets Editorial Team. Claims are source-checked under our editorial policy; clinician review is identified only when a named reviewer is shown.

What is Setmelanotide?

Setmelanotide is a synthetic cyclic peptide that activates the melanocortin-4 receptor, a key part of the brain pathway regulating hunger and body weight.

The approved populations have rare pathway defects; that biology is why results cannot be transferred to common polygenic obesity.

Why are people interested in it?

It is a practical example of genetically targeted obesity treatment and a counterpoint to broad 'weight-loss peptide' marketing.

Research continues in additional rare syndromic forms of obesity, but each requires its own evidence and regulatory review.

Current regulatory status

FDA approved for specific uses

The current Imcivree label covers adults and children age 2 and older with syndromic or monogenic obesity due to specified POMC, PCSK1, or LEPR deficiency or Bardet-Biedl syndrome. It excludes general obesity and unrelated genetic conditions.

What is it approved for?

  • Long-term reduction of excess body weight in eligible people age 2 and older with specified POMC, PCSK1, or LEPR deficiency or Bardet-Biedl syndrome

What is it being studied for?

POMC, PCSK1, and LEPR deficiency obesity
Bardet-Biedl syndrome
Other rare hypothalamic or syndromic obesity conditions
Hunger and hyperphagia outcomes

Investigational areas

  • Additional genetically or anatomically defined obesity syndromes

Evidence snapshot

Strong human evidence for approved uses

Human trials support weight and hunger outcomes in small rare-disease populations. The evidence is meaningful for those exact pathway disorders and does not establish benefit for common obesity.

Potential benefits being researched

  • Pivotal studies observed clinically important weight reduction in some people with rare MC4-pathway disorders.
  • The treatment can also reduce hunger in responsive patients, but response varies by genetic condition and person.

Potential does not mean proven. Study design, population, endpoint, and regulatory review matter.

Known or possible risks

  • The label warns about depression and suicidal thinking, sexual-arousal effects, serious hypersensitivity, and skin darkening or changes in existing moles.
  • Common adverse reactions include skin hyperpigmentation, injection-site reactions, nausea, headache, gastrointestinal symptoms, depression, and spontaneous erections.
  • The preservative benzyl alcohol poses serious risks to neonates and low-birth-weight infants; the product is not approved for infants.

What we still do not know

  • Long-term outcomes beginning in very young children
  • Which additional rare obesity disorders will respond
  • How benefits and risks compare across the small, genetically distinct approved groups
  • Effects in common obesity, where the drug is not indicated

Plain-English takeaway

Setmelanotide is not a niche version of a general weight-loss drug. It is a pathway-specific medicine whose value depends on the exact genetic or syndromic diagnosis.

Research and reference links

Use these primary and reputable sources to verify status and read beyond this summary. Trial registries may list studies without proving a benefit.

  1. 1
    FDA prescribing information: Imcivree

    Current indication beginning at age 2, population limits, warnings, and clinical evidence.

  2. 2
    FDA orphan-drug approvals: setmelanotide

    Official approval history for the rare genetic obesity indications.

  3. 3
    Phase 3 POMC and LEPR deficiency trials

    Pivotal human trials in severe obesity caused by POMC or LEPR deficiency.

  4. 4
    Phase 3 Bardet-Biedl syndrome trial

    Randomized trial supporting the Bardet-Biedl syndrome indication.