Setmelanotide
Also known as: Imcivree, RM-493
Key Facts: Setmelanotide
- Category
- Weight Loss
- FDA Status
- FDA Approved
- Clinical Status
- FDA Approved - Genetic obesities (BBS, POMC/PCSK1/LEPR deficiency) and acquired hypothalamic obesity (approved March 2026)
- Administration
- Subcutaneous injection daily
- Typical Dose
- 2-3 mg daily
- Frequency
- Once daily
- Duration
- Long-term / chronic use
Mechanism of Action
Setmelanotide activates melanocortin-4 receptors (MC4R) in the hypothalamus, restoring the satiety signaling pathway that is disrupted in certain genetic obesity syndromes. Works downstream of leptin signaling.
Research Summary
Approved for POMC, PCSK1, and LEPR deficiency obesity. Studies show significant weight loss in these specific populations where other treatments fail. Precision medicine approach. In March 2026, FDA approved an expanded indication for acquired hypothalamic obesity in adults and pediatric patients aged 4+. The Phase 3 TRANSCEND trial showed -18.4% placebo-adjusted BMI reduction.
Dosing Information
Typical Dosingⓘ
Community experience
2-3 mg daily
1-3 mg daily
Once daily
FDA-approved for specific genetic obesities (POMC, PCSK1, LEPR deficiency). Prescription only.
Research Dosingⓘ
Scientific studies
FDA-approved dosing
Doses from Studies
2-3 mg daily (adults)
Weight-based dosing (pediatric)
Duration
Long-term / chronic use
Administration
Subcutaneous injection daily
Timing & Administration
Best Time to Take
Before bed or morning (fasted)
Follow specific peptide protocol
Food Recommendation
Take on empty stomach
Why This Timing?
GH-related peptides work best on an empty stomach to maximize growth hormone release.
Possible Side Effects
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Skin hyperpigmentation (67-83%)
- ●Injection site reactions
- ●Nausea
- ●Spontaneous erections in males
- ●Priapism risk
- ●Depression risk
- ●FDA approved (Imcivree)
References
- https://pubmed.ncbi.nlm.nih.gov/32726212/
- https://pubmed.ncbi.nlm.nih.gov/32459923/
- https://pubmed.ncbi.nlm.nih.gov/34469589/
Research This Peptide Further
Frequently Asked Questions
What does Setmelanotide do?
An MC4R agonist for rare genetic obesity disorders. FDA approved for specific gene mutations causing obesity.
How does Setmelanotide work?
Setmelanotide activates melanocortin-4 receptors (MC4R) in the hypothalamus, restoring the satiety signaling pathway that is disrupted in certain genetic obesity syndromes. Works downstream of leptin signaling.
Is Setmelanotide FDA approved?
Yes, Setmelanotide is FDA approved. FDA Approved - Genetic obesities (BBS, POMC/PCSK1/LEPR deficiency) and acquired hypothalamic obesity (approved March 2026)
What are the side effects of Setmelanotide?
Reported side effects include: Skin hyperpigmentation (67-83%), Injection site reactions, Nausea, Spontaneous erections in males, Priapism risk. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Setmelanotide?
Community-reported common dose: 2-3 mg daily (Once daily). Range: 1-3 mg daily. Administration: Subcutaneous injection daily. Community-reported doses. Not medical advice. Consult healthcare provider.
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