Rankings / Metabolic Health

Setmelanotide

Metabolic Health · MC4R agonist

Tier B

Reviewed by Read Off Label · Last reviewed · How we grade

mc4rprescription
6.8 / 10
Tier B
Ev 8 Bn 8 Sf 5

Bottom line

Read Off Label grades Setmelanotide as B (6.8/10) based on strong evidence, high benefit magnitude, and a med-risk safety profile.

Approved for specific rare genetic obesity syndromes (POMC, PCSK1, LEPR deficiency, Bardet-Biedl); in the POMC trial 80% achieved ≥10% weight loss; requires genetic testing.

Studied, labeled, or reported-use context: Imcivree: 2-3 mg SC daily — Rx; not individualized guidance.

What the evidence says

Approved for specific rare genetic obesity syndromes (POMC, PCSK1, LEPR deficiency, Bardet-Biedl); in the POMC trial 80% achieved ≥10% weight loss; requires genetic testing. Mar 19 2026: FDA approved an expanded indication for acquired hypothalamic obesity (obesity after a hypothalamic tumor/injury or its treatment) in adults and children ≥4 — the first and only approved therapy for that condition — based on the Phase 3 TRANSCEND RCT (−18.4% placebo-adjusted BMI). EMA CHMP issued a positive opinion for the same indication (EU decision pending). Broadens setmelanotide beyond purely genetic syndromes to acquired hypothalamic disease, but remains a restricted, indication-specific drug — not a general obesity therapy. Jul 8, 2026: Phase 3 TRANSCEND results for acquired hypothalamic obesity published in NEJM (-16.5% vs +3.3% BMI change at 52 wk, p<0.001), the peer-reviewed confirmation of the Mar 2026 approval basis.

Mechanism

Selective melanocortin-4 receptor agonist; reactivates MC4R signaling in POMC-deficient, LEPR-deficient, PCSK1-deficient, or BBS patients, or after hypothalamic injury; hypothalamic appetite suppression

Studied, labeled, or reported dose & route

Imcivree: 2-3 mg SC daily

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

A link means the source informed this entry; it does not mean every claim on the page comes from that source. If a citation looks wrong or you want a claim re-checked, send a correction.

Common questions

What does the evidence show about Setmelanotide's effects?
Read Off Label rates the evidence for Setmelanotide as Strong and the benefit magnitude as high, producing an overall grade of B (6.8/10). Approved for specific rare genetic obesity syndromes (POMC, PCSK1, LEPR deficiency, Bardet-Biedl); in the POMC trial 80% achieved ≥10% weight loss; requires genetic testing.
What safety findings are reported for Setmelanotide?
Setmelanotide has a med risk profile in the database. Med (injection site reaction, hyperpigmentation, nausea) Legal status: Rx (restricted use; expanded Mar 2026 to acquired hypothalamic obesity).
What doses or routes are reported for Setmelanotide?
Imcivree: 2-3 mg SC daily This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does Setmelanotide work?
Selective melanocortin-4 receptor agonist; reactivates MC4R signaling in POMC-deficient, LEPR-deficient, PCSK1-deficient, or BBS patients, or after hypothalamic injury; hypothalamic appetite suppression

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.