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Melanocortin · Metabolic & endocrine

Setmelanotide

An MC4R agonist approved for specific genetic obesity syndromes — precision medicine, not a general weight-loss drug.

L4Strong humanApproved — narrow indicationApprovedHigh confidenceLast reviewed 2026-08-23
SC injection

Also known as: Imcivree, RM-493

Evidence passport

Last reviewed 2026-08-23

Evidence level
L4Strong human
Confidence
High confidence
Human efficacy
75/100
Human safety
70/100
Regulatory status
Approved — narrow indication
Development
Approved
Routes
SC injection
Evidence base
Includes human data
Furthest stage
Approved
Source curation
Sources fully curated
Clinical maturity
Approved for defined rare genetic obesity syndromes

Overview

Human evidence75/100
Preclinical evidence70/100
Human safety evidence70/100

Clinical maturity: Approved for defined rare genetic obesity syndromes

Routes & formulations

Studied / approved routes

SC injection

The approved product is a daily subcutaneous injection within the labelled genetic indications.

Route availability is not evidence of efficacy, and evidence from one route does not transfer to another. The Registry never provides dosing or sourcing information.

Peptide lifecycle

  1. Discovery

  2. Preclinical

  3. Phase I

  4. Phase II

  5. Phase III

  6. Approved

Approved

What it is

A peptide agonist of MC4R, the receptor at the heart of the brain's leptin-melanocortin appetite pathway — designed to restore signalling where specific genetic defects break it.

What people claim

  • Reduces weight in defined genetic obesity syndromes
  • Sometimes marketed as a general obesity drug

What the evidence actually says

In the defined genetic syndromes it was designed for, controlled trials showed meaningful weight and hunger improvements — a textbook example of matching a drug to a mechanism. In general obesity without those genetic defects, that evidence does not apply.

Human evidence

  • Pivotal trials in patients with POMC/PCSK1/LEPR-deficiency obesity and Bardet-Biedl syndrome supporting approval.

Preclinical evidence

  • MC4R pathway genetics and pharmacology in animal models.

Animal and cell findings are Level 1–2 evidence.

Mechanism and pathways

  • MC4R agonism restores appetite-regulation signalling downstream of the leptin pathway.

Safety and unknowns

  • Labelled effects include injection-site reactions, skin hyperpigmentation and nausea.
  • Use is tied to genetic confirmation of the indicated conditions.

Cancer relevance

No concern identified

No established human cancer signal within approved use.

Regulatory status

FDA-approved (Imcivree) for chronic weight management in adults and children with obesity due to specific genetically defined conditions (including POMC, PCSK1 or LEPR deficiency, and Bardet-Biedl syndrome, per current labelling). It is not a general obesity medication.

Evidence grade

L4Strong humanHigh confidence

Solid controlled human trials, though not yet definitive or fully replicated.

What would change our rating?

  • Long-term outcomes data in the approved rare populations.

References and sources

Sources fully curated

Source hierarchy: regulatory documents and trial registries first, peer-reviewed work next, sponsor material flagged as non-independent. We never use supplier or clinic marketing as evidence, and where a verified source has not yet been curated we say so rather than inventing one.

Evidence change history

No recorded changes yet. Baseline position set on 2026-08-23.

Related claims we’ve checked

MisleadingL4Strong humanMetabolic

“Setmelanotide is another general-purpose weight-loss GLP-1.”

Misleading — wrong mechanism, wrong population.

  • Setmelanotide is a melanocortin-4 receptor agonist, not a GLP-1; the drug class is different.
  • Its approval covers obesity due to specific genetically defined syndromes (such as POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome), confirmed by genetic testing.
  • It is not indicated for, and has not been shown to work as, a general obesity treatment.
Last reviewed 2026-08-23Compound profile