Also known as: IMCIVREE, RM-493, BMS-470539
Chronic weight management in genetic obesity (POMC, PCSK1, LEPR deficiency)
Amount
2-3 mg (adults/adolescents) or 1-3 mg (pediatric)
Frequency
Once daily
Duration
Ongoing (with 12-16 week response assessment)
Route
SCSchedule
Once daily
Timing
Administer once daily at the start of the day. Inject into the abdomen. Rotate injection sites with each injection.
Duration
Ongoing
Repeatable
Yes
Genetic testing
When: Before initiation (required)
Why: Confirm eligible POMC, PCSK1, or LEPR genetic variant
Body weight and BMI
When: Baseline and monthly
Why: Monitor weight loss response
CMP (Comprehensive Metabolic Panel)
When: Baseline
Why: Liver and kidney function baseline
Body weight assessment
When: 12-16 weeks at maintenance dose
Why: Determine if meaningful weight loss achieved; discontinue if not
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Setmelanotide (marketed as IMCIVREE) is a first-in-class melanocortin-4 receptor (MC4R) agonist developed by Rhythm Pharmaceuticals for the treatment of rare genetic forms of obesity. It was FDA-approved in November 2020 for chronic weight management in patients aged 6 years and older with obesity due to POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin type 1), or LEPR (leptin receptor) deficiency, confirmed by genetic testing demonstrating variants interpreted as pathogenic, likely pathogenic, or of uncertain significance.
Setmelanotide is a cyclic 8-amino acid peptide with a molecular weight of approximately 1.1 kDa. It represents the first targeted pharmacotherapy for monogenic obesity, a group of rare conditions caused by single-gene mutations in the hypothalamic MC4R signaling pathway that controls appetite and energy balance.
In June 2022, the FDA expanded the IMCIVREE indication to include Bardet-Biedl syndrome (BBS), broadening the potential patient population.
Setmelanotide works by directly activating the melanocortin-4 receptor (MC4R) in the hypothalamus:
The therapeutic rationale is specific to patients with genetic defects upstream of MC4R. In these patients, MC4R itself is intact but receives insufficient stimulatory input due to the upstream genetic defect.
Setmelanotide was evaluated in phase 3 trials in patients with POMC and LEPR deficiency obesity (Clement et al., 2020). The results demonstrated significant weight loss (mean ~25% body weight in POMC deficiency) and substantial hunger reduction, supporting the first FDA approval for a targeted obesity therapy in November 2020.
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, published in Lancet Diabetes & Endocrinology (Clement K et al., 2020; PMID: 33137293):
We summarize new studies, safety updates, and dosing insights โ delivered biweekly.
See real-world usage patterns alongside the clinical evidence above. Community-sourced, not clinically verified.
Based on 15+ community reports
View community protocolsAfamelanotide (Scenesse): FDA-approved MC1R agonist for erythropoietic protoporphyria. Subcutaneous implant increases pain-free sun exposure via melanogenesis.
Bivamelagon (LB54640): first oral MC4R agonist for hypothalamic obesity by Rhythm Pharmaceuticals. Phase 2 showed 9.3% BMI reduction at 14 weeks.
Melanotan-1 (Afamelanotide): Approved alpha-MSH analog. Covers melanocortin mechanism, Scenesse for EPP, photoprotective tanning, and safety data.
Melanotan-2: Cyclic melanocortin peptide for tanning and sexual function. Covers MC1R/MC4R activation, dosing protocols, side effects, and regulation.
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.
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