Setmelanotide (Imcivree®) (10mg)
Setmelanotide (Imcivree®) is an FDA-approved MC4R agonist from Rhythm Pharmaceuticals for rare genetic forms of obesity (POMC, PCSK1, LEPR deficiency, Bardet-Biedl). 10 mg vial — reconstitute in 2 mL for 5 mg/mL.
Reviewed by the AllPeptides.eu Editorial Team·Last reviewed: 2026-06-16
Educational information. Not medical advice, and no efficacy claim is implied. Regulatory approval is not a use recommendation by AllPeptides.eu.
⚠️ For informational/educational purposes only. Not medical advice. We do not sell any products. Self-treatment carries serious risks — consult a healthcare professional. Disclaimer
How It Works
Setmelanotide is a cyclic octapeptide that mimics α-MSH and selectively activates the melanocortin receptor MC4R in the hypothalamus. In patients with genetic deficiencies of the leptin-melanocortin pathway (POMC, PCSK1, LEPR), the satiety pathway is underactive, leading to hyperphagia and severe early-onset obesity. Setmelanotide bypasses the defect by directly activating MC4R on pro-opiomelanocortin neurons in the arcuate nucleus, restoring satiety and reducing energy intake. In Bardet-Biedl, the same pathway is functionally impaired due to ciliopathy.
Quick Start
- Reconstitution: 2.0 mL bacteriostatic water → 5 mg/mL.
- Adult Dose: 2–3 mg/day SC (max 3 mg).
- Pediatric Dose (6–11): 1–2 mg/day.
- Frequency: 1×/day, same time.
- Status: FDA approved (2020) — for approved genetic indications only.
Dosing Table — Setmelanotide 10mg (5 mg/mL)
Route: Subcutaneous injection | Frequency: 1× daily
| Week | Dose | Units (per injection) |
|---|---|---|
| Wks 1–2 (Adults) | 1 mg | 20 Units (0.20 mL) |
| Wks 3+ | 2 mg | 40 Units (0.40 mL) |
| Maintenance | 3 mg (max) | 60 Units (0.60 mL) |
| Pediatric 6–11 | 1–2 mg | 20–40 Units (0.20–0.40 mL) |
Per FDA guideline, titrate up every 2 weeks. Administer in the morning.
Related compounds
Reconstitution Steps
- Clean vial top with alcohol swab.
- Draw up 2.0 mL bacteriostatic water.
- Inject slowly onto the side wall — do not shake.
- Gently swirl until dissolved.
- Store at 2–8 °C.
Protocol Overview
- FDA approved (2020) for POMC, PCSK1, LEPR deficiency obesity.
- FDA approved (2022) for Bardet-Biedl syndrome (≥ 6 yrs old).
- Selective MC4R agonist — reactivates the underactive leptin-melanocortin pathway.
- In approved patients: 25–50% weight loss & 40% hunger reduction at 12 months.
- Not for common obesity — exclusive genetic indications (genetic confirmation required).
Dosing Protocol
- Start: 1 mg/day adults, 0.5 mg pediatrics.
- Titrate every 2 weeks.
- Max dose: 3 mg/day (adults).
- Discontinue if <5% weight loss at 12–16 weeks.
- Break between cycles: A 2–4 week break is recommended before repeating the cycle.
Washout & Cycle Restart
When can I restart?
After completing the cycle, a 2–4 week break is recommended before starting a new cycle. This allows the body to restore normal function and prevents potential downregulation (tachyphylaxis).
Storage Instructions
- Lyophilized: 2–8 °C, protect from light.
- Reconstituted: 2–8 °C, use within 42 days (FDA label).
- Do not freeze.
Important Notes
- For genetically confirmed indications only — not for common obesity.
- Transient skin darkening very common (reversible).
- Mole monitoring — changes in moles reported.
- Possible sexual side effects (priapism, increased libido).
- This protocol is for educational purposes only.
Regulatory Status
Setmelanotide (Imcivree®) was approved by the FDA in 2020 as the first targeted treatment for specific rare genetic forms of obesity. Approval requires genetic confirmation. Use outside the approved indications (common obesity) is not supported by the regulatory authority.
FDA — NDA 213793Potential Benefits & Side Effects
Potential Benefits:
- FDA & EMA approved for specific genetic indications.
- Dramatic weight loss in approved patients.
- Hunger reduction ~40% at 12 months.
- Effective in children ≥6 years old (BBS, POMC).
- Personalized therapy based on genetic testing.
Potential Side Effects:
- Transient skin hyperpigmentation (very common).
- Nausea, diarrhea, vomiting (initially).
- Mole changes — requires dermatological monitoring.
- Sexual side effects (increased libido, rare priapism).
- Injection site reactions.
- Depression/suicidal ideation — monitoring required.
⚠️ Serious Warnings & Long-Term Risks
The following warnings are based on published literature, FDA labels, and post-marketing surveillance. They do not constitute medical advice. Consult a healthcare professional.
Nevus changes and hyperpigmentation
Setmelanotide is associated with skin hyperpigmentation and nevus changes, so dermatologic monitoring is part of the approved context.
📄 FDA Label — Imcivree®Depression and suicidal ideation
The Imcivree label includes monitoring for depression and suicidal ideation during therapeutic use.
📄 FDA Label — Imcivree®References
- FDA Approval — Imcivree (2020) — Setmelanotide for POMC, PCSK1, LEPR deficiency obesity.
View Source - Lancet Diabetes Endocrinol (2020) — Clément K, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency.
View Source - Bardet-Biedl trial (2022) — Haqq AM, et al. Setmelanotide trial for BBS. Lancet Diabetes Endocrinol. 2022.
View Source - EMA EPAR — Imcivree — European Medicines Agency public assessment report.
View Source - MC4R pharmacology — Collet TH, et al. Evaluation of a melanocortin-4 receptor agonist in POMC deficiency. Mol Metab. 2017.
View Source
Recommended Supplements
Vitamin B12 (Methylcobalamin)
Vitamin D3 + K2
Omega-3 Fish Oil (EPA/DHA)
Protein / Collagen
Fiber Supplement (Psyllium)
External Sources & Regulatory Status
Regulatory Approvals
Imcivree® · Rare genetic forms of obesity (2020)
Imcivree® · Rare genetic forms of obesity (2021)
FDA + EMA approved for specific genetic indications
Educational information. Not medical advice, and no efficacy claim is implied. Regulatory approval is not a use recommendation by AllPeptides.eu.
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