Setmelanotide
Also known as: Imcivree, RM-493
Molecular Identifiers
Overview
Selective melanocortin 4 receptor (MC4R) agonist, developed for the treatment of genetically-driven obesity. Acts by restoring leptin-melanocortin pathway signaling, essential for appetite regulation and energy expenditure.
Approved by the FDA as Imcivree (2020) for the treatment of rare genetic obesity caused by POMC, PCSK1, or leptin receptor (LEPR) deficiency, in patients 6 years of age and older.
Ac-Arg-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys-NH₂ Cyclic peptide with non-natural amino acids
Half-life
~11 hours
Administration Route
Subcutaneous
Category
Metabolic & Fat Loss
Mechanism of Action
- Selective MC4R receptor agonism in the hypothalamus
- Restoration of the leptin-POMC-MC4R pathway signaling
- Appetite reduction and increased satiety
- Increased basal energy expenditure
- Lipid metabolism modulation via central signaling
Dosage Protocol
Data compiled from the literature. This does not constitute medical advice.
| Parameter | Value |
|---|---|
| Dose | 1-3 mg per day (subcutaneous) |
| Frequency | Once daily |
| Timing | Morning, consistent time |
| Duration | Continuous use (chronic treatment for genetic obesity) |
Reported Side Effects
Adverse effects described in the literature. Severity and frequency vary between individuals.
- Injection site reactions
- Hyperpigmentation
- Nausea
- Diarrhea
- Abdominal pain
Presentations & Preparation
Vials of Setmelanotide found in the research market:
Reconstitution
- Diluent: Bacteriostatic water
- Volume: 1 ml per vial
- Inject the diluent slowly against the vial wall
- Gently swirl until completely dissolved — never shake
- Gradual dose escalation recommended (1 mg → 2 mg → 3 mg)
Storage
- Lyophilized: Refrigerated 2-8°C
- Reconstituted: Refrigerated 2-8°C (up to 30 days)
- Protect from direct light
- Do not freeze after reconstitution
Scientific Studies
Published studies on Setmelanotide.
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
Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, De Waele K, Farooqi IS, et al.
Efficacy and safety of setmelanotide in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Haqq AM, Chung WK, Dolber T, Haws RM, Mitchell JA, Nissen SE, Rees AH, Sethi M, Stewart M, Yuan G, Clément K
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