Setmelanotide
Also known as: Imcivree, RM-493
MC4 receptor agonist, FDA-approved in 2020 as Imcivree for rare genetic and hypothalamic obesity. Not for general obesity. Prescription medication.
Last updated
Mechanism of Action
Setmelanotide is a cyclic peptide agonist of the melanocortin-4 receptor (MC4R) in the hypothalamus. In rare disorders where the leptin-melanocortin pathway is broken upstream of MC4R, such as POMC, PCSK1 or LEPR deficiency, Bardet-Biedl syndrome, or hypothalamic damage, it restores the satiety signal that the missing hormones would normally provide, reducing hunger and body weight. It also acts on the melanocortin-1 receptor, which explains the skin darkening seen with treatment.
- Half-life
- ~11 hours
- Administration Routes
- Subcutaneous
- Research Status
- Clinical
Reported Benefits
- Weight and hunger reduction in obesity due to POMC, PCSK1 or LEPR deficiency
- Approved for obesity in Bardet-Biedl syndrome (2022)
- Approved for acquired hypothalamic obesity in patients 4 years and older (2026)
Potential Side Effects
- Skin hyperpigmentation
- Injection-site reactions
- Nausea, vomiting and headache
- Depression and suicidal ideation (warning)
- Spontaneous penile erections; adrenal insufficiency reported in hypothalamic obesity
Common Dosing
Labeled dosing is a once-daily subcutaneous injection, starting low and titrated by age and tolerability; it is used only after the qualifying genetic diagnosis or hypothalamic obesity is confirmed. Dosing is set and supervised by the prescribing clinician.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Prior serious hypersensitivity to setmelanotide
- Not indicated for common (polygenic) obesity or for benign or likely benign gene variants
- Pregnancy: label advises stopping once pregnancy is recognized
No documented stacking partners for Setmelanotide yet.
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Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials
2020
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Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period
2022
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Setmelanotide for the Treatment of Acquired Hypothalamic Obesity
2026