Setmelanotide
Aliases: Imcivree
Last verified: 2026-09-23
The short version
An MC4R agonist — approved for rare genetic obesities (POMC, PCSK1, LEPR deficiencies, Bardet-Biedl). The first drug that "repairs" a broken melanocortin pathway.
Identity & type
- Molecular type
- analog
- Origin
- An MC4R agonist — approved for rare genetic obesities (POMC, PCSK1, LEPR deficiencies, Bardet-Biedl).
Mechanism of action
Direct MC4R activation in the hypothalamus → restores satiety signaling in upstream genetic defects.
Dosing & routes
Official / clinical context
Approved drug — indications, dosing and warnings are defined by the official label. Titrated to 3 mg SC daily.
Regulator-approved labeling and published study designs — never a recommendation.
Community-reported practice
Titrated to 3 mg SC daily. In rare genetic obesities: dramatic reduction of hyperphagia and weight; the community outside the indication does not use it (it only targets specific mutations).
Unverified self-reports. Not medical advice. Not endorsement.
Expected effects (community)
In rare genetic obesities: dramatic reduction of hyperphagia and weight; the community outside the indication does not use it (it only targets specific mutations).
Protocol — official vs community
Official / label
Imcivree, for chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency, or Bardet-Biedl syndrome: 2 mg SC once daily (pediatric dosing weight-based).
- 01Start: 2 mg once daily
- 02After ≥2 weeks, may increase to 3 mg once daily in patients not adequately responding and tolerating 2 mg
Duration: Chronic while the genetic indication persists; weight regain follows discontinuation.
Roughly 80% of genetically confirmed POMC/LEPR patients in phase 3 lost ≥10% of body weight — among the largest indication-response couplings in obesity pharmacology. Skin darkening and spontaneous erections are on-mechanism (MC1R/MC4R) effects.
Community (anecdotal)
Structured protocol data for this entry is coming.
Human evidence
Phase III: ~80% of POMC/LEPR patients achieved ≥10% weight loss; broader indications (hypothalamic obesity) studied.
Preclinical evidence
The preclinical phase was completed and submitted to regulators as part of registration; pharmacology and toxicology details are part of the official label.
Known risks
- Skin darkening (MC1R), injection-site reactions, nausea, spontaneous erections.characterized
Teal: characterized in clinical/labeling contexts. Amber: theoretical or reported outside controlled settings.
Unknowns & evidence gaps
- Real-world data outside controlled trials