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Setmelanotide Reference
Educational, not medical advice reference for Setmelanotide: Fat Loss, Hormonal, Metabolic; regulatory status, evidence posture, source review,…
Reference summary
Setmelanotide is a synthetic cyclic 8-residue alpha-MSH analog acting as a selective melanocortin-4 receptor (MC4R) agonist; it bypasses upstream defects in the leptin-melanocortin pathway by supplying the missing receptor ligand directly. Pivotal evidence: Clement 2020 Lancet Diabetes Endocrinol (PMID 33137293) reported 8/10 (80 percent) POMC/PCSK1 deficiency patients and 5/11 (about 45 percent) LEPR deficiency patients achieving at least 10 percent body weight reduction at approximately 1 year in single-arm open-label trials with placebo-controlled withdrawal periods. Haqq 2022 Lancet Diabetes Endocrinol (PMID 36356613) reported about 32 percent of BBS patients aged 12 and older achieving at least 10 percent body weight reduction at 52 weeks in a multicentre randomised double-blind placebo-controlled trial with an open-label period; the Alstrom syndrome subgroup did not reach the same threshold and the BBS approval is BBS-specific. pepSmart surfaces label-reference content only.
Regulatory and posture
- Categories
- Fat Loss, Hormonal, Metabolic
- Aliases
- Imcivree, RM-493, MC4R agonist
- Evidence posture
- human - Approved only for narrow rare-disease obesity indications: Bardet-Biedl syndrome and confirmed POMC / PCSK1 / LEPR deficiency (genetic testing required), plus acquired hypothalamic obesity. Not approved for general weight loss or heterozygous variant carriers. Skin hyperpigmentation, darkening of pre-existing nevi, depression / suicidal ideation signal, spontaneous penile erection in males, and disturbance in sexual arousal in females are label-level warnings.
- Regulatory status
- FDA-approved prescription medication (Imcivree, Rhythm Pharmaceuticals). Initial US approval November 25, 2020 for POMC, PCSK1, and LEPR deficiency. Supplemental approval June 16, 2022 added Bardet-Biedl syndrome (BBS). December 20, 2024 label expansion lowered the indicated-age floor from 6 years to 2 years for the BBS, POMC, PCSK1, and LEPR populations. A subsequent supplemental approval on March 19, 2026 added acquired hypothalamic obesity (age 4 and older) as a third indication, supported by the Phase 3 TRANSCEND trial. Indicated only for chronic weight management in (a) adults and pediatric patients age 2 years and older with obesity due to BBS; (b) adults and pediatric patients age 2 years and older with monogenic obesity due to confirmed POMC, PCSK1, or LEPR deficiency; (c) adults and pediatric patients age 4 years and older with acquired hypothalamic obesity. Not indicated for general or polygenic obesity. Prescription-only; clinician-managed.
- Content review status
- label verified
Selected public sources
- DailyMed setmelanotide (Imcivree) prescribing information
- FDA news: FDA Approves First Treatment for Weight Management for People with Certain Rare Genetic Conditions (Imcivree, setmelanotide, November 25, 2020)
- FDA news: Imcivree (setmelanotide) supplemental approval for Bardet-Biedl syndrome (June 16, 2022)
- Rhythm Pharmaceuticals: FDA approval of IMCIVREE (setmelanotide) for acquired hypothalamic obesity (March 19, 2026)
- PubMed: Clement K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol 2020;8(12):960-970 (PMID 33137293)
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