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.

Typical use: Imcivree: 2-3 mg SC daily — Rx.

What this is

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.

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

Dose & route

Imcivree: 2-3 mg SC daily

Citations

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Common questions

Does Setmelanotide work?
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.
Is Setmelanotide safe?
Setmelanotide has a med risk profile in published human data. Legal status: Rx (restricted use; expanded Mar 2026 to acquired hypothalamic obesity). This is not medical advice — see the disclaimer.
What is the typical dose for Setmelanotide?
Imcivree: 2-3 mg SC daily
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.