Hormonal & Sexual Health

Setmelanotide

Setmelanotide is a manufactured copy of the brain signal that switches hunger off, given to people in whom that switch is genetically broken. It acts at the melanocortin-4 receptor, one step downstream of leptin, so it restores a pathway rather than adding a new one, which is why the approval is written by genotype rather than by weight. Sold as Imcivree and cleared by the FDA in 2020, it covers obesity caused by faults in POMC, PCSK1 or the leptin receptor, and was later extended to Bardet-Biedl syndrome. The randomised evidence was generated in exactly those populations, and it does not transfer to common obesity.

Last updated 12 August 2026

Studied forMonogenic obesity treatment · Hunger score reduction · Body weight research

Evidence on fileFDA-approved · 2 randomised human trials

Strongest sourceEfficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC… (randomised human trial)

Mechanism

Agonist at the melanocortin-4 receptor, restoring hypothalamic hunger, satiety, and energy-expenditure signalling downstream of leptin.

Regulatory status

Approved by the FDA. Marketed as IMCIVREE. Earliest approval 2020-11-25. Application NDA213793.

An approval grades as rung 1 on this site, because 21 CFR 314.126 requires adequate and well-controlled human investigations and one cannot be granted without them. It covers specific indications and doses, though, and does not transfer to other uses of the same molecule.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

Monogenic obesity treatment
Hunger score reduction
Body weight research

Dosing on file unverified

Start: 0.5 mg QD × 2 weeks; Target: 3 mg QD (adults/peds ≥6 yrs); Titrate 1.5-3.0 mg by age/weight

Carried from a source that labels it unverified, and reproduced with that label attached. A record of what is reported, not a recommendation. No citation on this page establishes it.

How it is given

With food: No restriction. label “Administer IMCIVREE once daily, at the beginning of the day, without regard to meals.” IMCIVREE FDA prescribing information, dosage & administration.
Not by: intravenous and intramuscular — ruled out by the label, which is a different fact from a route nobody has recorded. “Do not administer IMCIVREE intravenously or intramuscularly.” label IMCIVREE FDA prescribing information, dosage & administration.

Half-life, storage & sport

Elimination half-life: 11 hours (human, SC) — study. IMCIVREE FDA prescribing information, section 12.3.

The half-life on file is 11 h, measured subcutaneously. On the schedule this record states — daily — each dose is still at 22% of its own peak when the next is given, so the doses overlap: the peaks build to 1.28× the first.

Dosed daily over 4 d, each dose normalised to the first peak.

The rise is not modelled and the axis is not a blood level. No absorption rate constant and no volume of distribution are on file, so each dose appears at full height the instant it is given, and the axis is percent of this compound's own peak.

Literature on file 3

human RCT
Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency (The Lancet Diabetes & Endocrinology 2020, cited 442x) graded on: a phase 2b/3 trial — the indexed publication type — “Trial, Phase III”
human RCT
Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome (The Lancet Diabetes & Endocrinology 2022, cited 183x) graded on: names a randomised controlled trial — the indexed publication type — “Randomized Controlled”
human RCT
FDA approval NDA213793 graded on: an FDA approval (NDA213793), which requires adequate and well-controlled human investigations — “NDA213793”

Identity

Space-filling 3D model of Setmelanotide, carbon grey, nitrogen blue, oxygen red — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

2D chemical structure of Setmelanotide — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

Molecular weight: 1117.3
Molecular formula: C49H68N18O9S2
CAS number: 920014-72-8
PubChem CID: 11993702
InChI key: HDHDTKMUACZDAA-PHNIDTBTSA-N
Sequence: RCAHFRWC
SMILES: C[C@@H]1C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N)CC2=CNC3=CC=CC=C32)CCCN=C(N)N)CC4=CC=CC=C4)CC5=CN=CN5
InChI: InChI=1S/C49H68N18O9S2/c1-26-41(70)63-37(20-30-22-55-25-59-30)46(75)64-35(18-28-10-4-3-5-11-28)44(73)62-34(15-9-17-57-49(53)54)43(72)65-36(19-29-21-58-32-13-7-6-12-31(29)32)45(74)66-38(40(50)69)23-77-78-24-39(47(76)60-26)67-42(71)33(61-27(2)68)14-8-16-56-48(51)52/h3-7,10-13,21-22,25-26,33-39,58H,8-9,14-20,23-24H2,1-2H3,(H2,50,69)(H,55,59)(H,60,76)(H,61,68)(H,62,73)(H,63,70)(H,64,75)(H,65,72)(H,66,74)(H,67,71)(H4,51,52,56)(H4,53,54,57)/t26-,33+,34+,35-,36+,37+,38+,39+/m1/s1

Notes unverified prose

FDA-approved (Imcivree); TRANSCEND trial; DailyMed

Not on file 0

All 8 tracked fields hold a value on this record: molecular weight and formula, CAS number, PubChem CID, amino-acid sequence, SMILES, InChI and InChI key.

Counted from the record itself, not from what a source said it was missing. 163 of 188 records still have at least one empty.

At a glance

Strongest rung: human RCT
Citations: 3
Regulatory: FDA approved
Route: Subcutaneous
Not by: intravenous, intramuscular
Declared gaps: 0

Citations by rung

human RCT3

Strongest wins, never an average.