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Setmelanotide (Imcivree)

Peptide

Setmelanotide (brand name Imcivree) is an 8-amino-acid cyclic peptide that acts as a selective melanocortin-4 receptor (MC4R) agonist. It was FDA-approved in November 2020 as the first therapy for chronic weight management in patients with obesity due to POMC, PCSK1, or LEPR deficiency, and in 2022 for Bardet-Biedl syndrome (BBS). It works by restoring MC4R pathway signaling to reduce hyperphagia and promote weight loss.

Quick Answer

What it is

Setmelanotide (brand name Imcivree) is an 8-amino-acid cyclic peptide that acts as a selective melanocortin-4 receptor (MC4R) agonist. It was FDA-approved in November 2020 as the first therapy for chronic weight management in patients with obesity due to POMC, PCSK1, or LEPR deficiency, and in 2022 for Bardet-Biedl syndrome (BBS).

Key findings

  • Grade A: Weight Loss (POMC/PCSK1 Deficiency) (Obesity)
  • Grade A: Weight Loss (LEPR Deficiency) (Obesity)
  • Grade A: Weight Loss (Bardet-Biedl Syndrome) (Obesity)

Safety

No specific caution or interaction language was detected in the current summary/outcome notes.

⚠ Research Notice

This peptide information is for educational and research purposes only. Peptides may not be FDA-approved for human use and may only be legally available for research purposes. Consult qualified healthcare professionals before considering any peptide compounds.

â„č Quick Facts: Setmelanotide (Imcivree)

Quick Facts: Setmelanotide (Imcivree)

  • Best Evidence:Grade A
  • Conditions Studied:2
  • Research Outcomes:11
  • Grade A Findings:5
  • Grade B Findings:4
  • Key Effect:Obesity
A5
B4
C0
D2
2 conditions · 11 outcomes

Detailed Outcomes

|
A
Weight Loss (POMC/PCSK1 Deficiency)
80% of participants with POMC/PCSK1 deficiency achieved at least 10% weight loss at 1 year in Phase 3 trials.
large↓Improves
A
Weight Loss (LEPR Deficiency)
45% of participants with LEPR deficiency achieved at least 10% weight loss at 1 year in Phase 3 trials.
large↓Improves
A
Weight Loss (Bardet-Biedl Syndrome)
Phase 3 trial showed significant weight reduction in BBS patients after 1 year, with mean change of -5.5% body weight at 3 months in Phase 2.
moderate↓Improves
B
Quality of Life
After 1 year of treatment, patients reported clinically meaningful improvements across multiple health-related quality of life measures.
moderate↑Improves
B
Resting Energy Expenditure
Setmelanotide has been shown to increase resting energy expenditure in both animal models and humans with obesity.
small↑Improves
A
Hunger Reduction
Significant improvements in hunger scores were observed in all cohorts (POMC, LEPR, and BBS) with setmelanotide treatment.
large↑Improves
A
Hyperphagia Control
Setmelanotide reduced hyperphagia and obsessive focus on food in patients with genetic obesity syndromes, improving daily functioning.
large↓Improves
B
Body Weight
48 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.
moderate↓Improves
B
Safety/Tolerability
5 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.
small↑Improves
D
Anti-Inflammatory Activity
2 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
D
Blood Glucose Control
2 human trials support this finding. Human clinical trial data available.
small↓Improves

Research Citations (37)

Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.
(2025)
PMID: 41002740
Real-life experience on efficacy and safety of setmelanotide treatment in prepubertal children.
(2025)
PMID: 39891402
Adverse event profile of setmelanotide in obesity: an integrated assessment and systematic review using disproportionality analysis, case reports and meta-analysis.
(2025)
PMID: 39924461
Real-World Efficacy and Safety of Setmelanotide in Adults With Monogenic or Syndromic Obesity: A Prospective Cohort Study.
(2025)
PMID: 40897637
Risk of Glaucoma in Patients without Diabetes Using a Glucagon-Like Peptide 1 Receptor Agonist.
(2025)
PMID: 39978437
Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.
(2025)
PMID: 39549719
Current and Emerging Parenteral and Peroral Medications for Weight Loss: A Narrative Review.
(2025)
PMID: 40422561
Management of Acquired Hypothalamic Obesity After Childhood-Onset Craniopharyngioma-A Narrative Review.
(2025)
PMID: 40426846
Approach to Obesity Treatment in Primary Care: A Review.
(2024)
PMID: 38466272
Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial.
(2024)
PMID: 38697184