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Setmelanotide

MC4R Agonist (selective) / Anti-Obesity

Also known as: Imcivree · RM-493

An FDA-approved selective MC4R agonist for rare genetic obesity disorders including POMC, PCSK1, & LEPR deficiency. The most targeted melanocortin anti-obesity drug.

Typical Dose

2–3 mg once daily (FDA-approved dosing)

Route

Subcutaneous injection (once daily)

Cycle

Continuous (approved for ongoing use)

Half-life

~11 hours

Storage

2–8°C. Multi-dose vials: room temp up to 30 days after first use.

Overview

Setmelanotide is a cyclic octapeptide that selectively activates melanocortin 4 receptor (MC4R) in the hypothalamus to restore satiety signaling in patients with specific genetic obesity disorders. It received FDA approval in 2020 for obesity due to POMC, PCSK1, or LEPR deficiency — conditions where the natural MC4R signal pathway is broken.

Unlike Melanotan II (non-selective) or PT-141 (MC3R/MC4R), Setmelanotide's selectivity for MC4R means minimal tanning (low MC1R activity) & sexual side effects. In approved indications, it produces significant & durable weight loss in patients who are otherwise unresponsive to lifestyle or other drug interventions.

Quick Start Guide

1

FDA-approved for specific genetic diagnoses only. Administered as 2–3 mg SubQ daily via injection pen under physician supervision.

Research Indications

Genetic obesity (POMC/PCSK1/LEPR deficiency)

Most Effective

FDA approved. Phase III: significant mean weight reduction in patients with defined MC pathway defects.

Research Protocols

FDA-approved therapeutic use

Continuous

Dose

2–3 mg once daily

Frequency

Daily SubQ

Route

SubQ abdomen or thigh

Peptide Interactions

PT-141Monitor

Both act on MC4R. Do not combine.

Side Effects & Safety

Common

  • Injection site reactions
  • Hyperpigmentation (nevi darkening)
  • Nausea
  • Headache

Uncommon

  • Spontaneous penile erections
  • Diarrhea

When to Stop

  • Signs of allergic reaction
  • Suicidal ideation (monitor in pediatric use)

How to Reconstitute

1

Provided as pre-filled injection cartridge. See prescribing information for administration details.

Dosing math: Commercial product only. Not typically compounded.

Quality Indicators

Good — use as normal

  • Clear, colorless solution (commercial product)

Discard immediately

  • Discoloration or particulate in commercial vial

What to Expect

Month 1

Appetite suppression begins. Weight loss commences in responsive patients.

Month 3–6

Substantial weight loss in approved genetic indications. Effect plateaus at new set point with continued use.

Community Insights

Self-reported. Reflects user experience, not clinical outcomes.

Research References

Efficacy & Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obesity Due to POMC or LEPR Deficiency

New England Journal of Medicine · 2019

Phase III: significant weight loss in 100% of patients with POMC deficiency & 45% of LEPR deficiency patients.

doi:10.1056/NEJMoa1911362

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Information on this page applies to pharmaceutical-grade peptides. Purity & identity of research-grade products vary. Certipep provides independent ESI-TOF-MS & HPLC analysis with a signed analytical report.

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