Setmelanotide
Also known as: Imcivree, RM-493, BIM-22493
Setmelanotide activates MC4R in specific rare obesity disorders. Its approved genetic and acquired hypothalamic indications differ from common obesity, with distinct age limits and safety monitoring.
Quick Facts
MC4R treatment for selected obesity disorders
Setmelanotide, sold as Imcivree and developed as RM-493/BIM-22493, is a peptide agonist of melanocortin-4 receptors. It addresses severe hunger and obesity arising from selected disrupted appetite-signaling pathways, including rare genetic disease and acquired hypothalamic damage. First US approval came in 2020; it is not approved for common obesity.
Bypassing an impaired upstream signal
In the leptin–melanocortin pathway, information from fat stores passes through POMC, PCSK1 and LEPR-related signaling before MC4R. Relevant upstream defects can leave MC4R inadequately stimulated and produce severe early-onset hunger and obesity. Setmelanotide directly stimulates MC4R, bypassing that defective step. Genetic indications require confirmation of the specific condition.
In pivotal trials, approximately 80% of participants with POMC deficiency and 45% with LEPR deficiency lost at least 10% of body weight over about one year, with lower hunger scores. Mild activation of related pigment receptor MC1R explains the expected skin-darkening effect.
Supporting references: loss.
Sources: [1]
Indication and age boundaries
| Indication | Approval | Ages in the reported current label |
|---|---|---|
| Confirmed POMC, PCSK1 or LEPR deficiency obesity | 2020 | 2 years and older; age reduced since initial approval |
| Bardet–Biedl syndrome obesity | 2022 | 2 years and older; age reduced since initial approval |
| Acquired hypothalamic obesity | March 2026 | Adults and children 4 years and older |
Supporting references: approved.
Sources: [2]
Chronic weight management in the relevant diagnosis
Imcivree is used to reduce excess body weight and maintain the reduction in the specified deficiencies, Bardet–Biedl syndrome and acquired hypothalamic obesity. A diagnosis-specific indication should not be generalized to usual obesity or to every hypothalamic or genetic finding.
The medicine is administered by daily subcutaneous injection for the applicable diagnosis and age group.
Skin, mood, sexual and endocrine risks
Common effects include hyperpigmentation of skin and moles, injection reactions, nausea, vomiting, diarrhea, abdominal pain, headache, depression and spontaneous erections in males. Skin examinations are relevant to pigment and mole changes. Serious issues include depression and suicidal thoughts requiring monitoring, sexual-arousal disturbances including reactions in females, and serious allergy. Acquired hypothalamic obesity also brings concerns about acute adrenal insufficiency and sodium imbalance. The benzyl-alcohol preservative requires caution in newborns and low-birth-weight infants.
References and further reading
This reference draws on Superpower’s Peptide Library and the research linked below. Peptide Dossier’s editorial team adapted and integrated the material on .
- 10.1016/S2213-8587(20)30364-8Bypassing an impaired upstream signalCited in: Bypassing an impaired upstream signal
- accessdata.fda.govIndication and age boundariesCited in: Indication and age boundaries
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Disclaimer: This article is for informational and educational purposes only. It is not intended as medical advice. The information presented is based on published research and should not be used as a substitute for professional medical guidance. Always consult a qualified healthcare provider before starting any peptide protocol. Some peptides discussed may not be approved for human use by the FDA or equivalent regulatory bodies.