Peptide LibrarySetmelanotide
Also known as: Imcivree, RM-493, MC4R agonist
Setmelanotide (also called Imcivree or RM-493) is an FDA-approved MC4R agonist. Setmelanotide is a cyclic peptide agonist selective for the melanocortin-4 receptor. MC4R sits at the bottom of the leptin-melanocortin pathway: leptin signals adiposity to the hypothalamus, POMC neurons release alpha-MSH, and alpha-MSH acts at MC4R to suppress appetite.
For research use only.
Key Facts
- CAS
- 920014-72-8
- Molecular Weight (MW)
- 1117.3 g/mol
- Half-life
- ~11 hours
- FDA status
- Approved
- Evidence level
- FDA Approved
- Human dose established
- Yes
- Administration Route
- Subcutaneous
- Frequency
- Once daily
- Last updated
- Sep 6, 2026
- Reviewed
- Sep 5, 2026
- Targets
- MC4R
Research summary
FDA-approved MC4R agonist (Imcivree) for rare genetic obesities (POMC, PCSK1, LEPR deficiency, Bardet-Biedl). Daily SC injection, not a general-obesity drug.
Research evidence
- Regulatory review (FDA label)1 reviewed source
- Controlled human trials3 reviewed sources
- Early or uncontrolled human studiesNone in reviewed sources
- Lab & animal studiesNone in reviewed sources
How it works
Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.
Peptide Library's Setmelanotide profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Setmelanotide dosage evidence
Setmelanotide has an FDA-approved human dosage. As Imcivree it is titrated to a maintenance dose of 3 mg subcutaneously once daily in patients aged 6 and over, starting at 0.5 mg or 2 mg depending on indication and age, with weight-based dosing for children aged 2 to 6. Every approved use is a rare genetic or acquired melanocortin-pathway obesity, not general weight loss.
| Human dosing established | Yes |
|---|---|
| Studied dose range | 0.5–3 mg once daily, titrated |
| Route | Subcutaneous |
| Frequency | Once daily |
| Duration studied | Continuous |
| Titration | Stepwise over 2–8 weeks by tolerance and age group, with specific protocols for managing gastrointestinal effects. Starting dose is 0.5 mg for acquired hypothalamic obesity aged 4+, or 2 mg for patients aged 12+ with Bardet-Biedl syndrome or POMC/PCSK1/LEPR deficiency. |
| Evidence level | FDA Approved |
| Last reviewed | 2026-09-05 |
Research-reported dosing
Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| FDA label — ImcivreeFDA-approved label · FDA prescribing information | Patients aged 4+ with acquired hypothalamic obesity; aged 2+ with Bardet-Biedl syndrome; aged 2+ with confirmed POMC, PCSK1 or LEPR variants | 3 mg maintenance for ages 6+; weight-based for ages 2–6 | Subcutaneous | Once daily | Continuous | Reduction of excess body weight | IMCIVREE (setmelanotide) injection — FDA prescribing information, DailyMed |
| Phase 3 — acquired hypothalamic obesity (2026)Clinical trial · Phase 3 randomised trial | Patients with acquired hypothalamic obesity | Per trial protocol, titrated | Subcutaneous | Once daily | Per trial protocol | Body mass index reduction | Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med. 2026. |
| NCT03746522 — phase 3, Bardet-Biedl syndrome, results postedClinical trial · Phase 3 trial with posted results | Patients with Bardet-Biedl syndrome (n=52) | Per trial protocol | Subcutaneous | Once daily | — | Weight and hunger scores | NCT03746522 — Setmelanotide (RM-493), MC4R Agonist, in Bardet-Biedl Syndrome |
| NCT03287960 — phase 3, LEPR deficiency, results postedClinical trial · Phase 3 trial with posted results | Patients with leptin receptor deficiency obesity (n=15) | Per trial protocol | Subcutaneous | Once daily | — | Weight reduction | NCT03287960 — Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity |
Where sources disagree
- The approved dose is indication- and age-specific, and the starting dose differs fourfold between indications (0.5 mg versus 2 mg). A single "setmelanotide dose" figure is not meaningful without naming the population.
- Every approved indication is a rare melanocortin-pathway disorder — Bardet-Biedl syndrome, POMC/PCSK1/LEPR deficiency, acquired hypothalamic obesity. Setmelanotide is not approved for common obesity, and the trial populations were small and genetically defined.
- Setmelanotide is a melanocortin-4 receptor agonist, mechanistically related to melanotan II and bremelanotide but with a different receptor selectivity profile. Dosing does not transfer between them.
Handling & administration
- Reconstitution Guide
- Reconstitute with sterile water for injection per package insert
- Injection Sites
- AbdomenThighUpper arm
- Concentration Example
- Vial contains lyophilized powder - reconstitute per package insert
- Timing Notes
- Inject subcutaneously in abdomen, thigh, or upper arm, preferably at same time each day
- Expected Onset
- Weight loss typically begins within 2-4 weeks
How to reconstitute Setmelanotide
- Check the vial size and diluent volume. The profile example for Setmelanotide is: Reconstitute with sterile water for injection per package insert.
- Swab both vial stoppers and draw the bacteriostatic water into a sterile syringe.
- Add the water slowly down the inside wall of the peptide vial so it does not jet onto the powder, then swirl gently until the solution is clear. Do not shake.
- Record the resulting concentration: Vial contains lyophilized powder - reconstitute per package insert.
- Label the vial with the date and concentration, refrigerate it (see Storage & stability below), and use the calculator preset to convert a dose in mcg into syringe units.
Sequence & molecular data
| Molecular formula | C49H68N18O9S2 |
|---|---|
| Molecular weight | 1117.3 g/mol |
| CAS number | 920014-72-8 |
| Half-life | ~11 hours |
| Appearance | Sterile solution for subcutaneous injection |
| Formulation | Solution |
| PubChem CID | 11993702 |
| FDA UNII | N7T15V1FUY |
| ChEMBL | CHEMBL3301624 |
| DrugBank | DB11700 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
Setmelanotide is a cyclic peptide agonist selective for the melanocortin-4 receptor. MC4R sits at the bottom of the leptin-melanocortin pathway: leptin signals adiposity to the hypothalamus, POMC neurons release alpha-MSH, and alpha-MSH acts at MC4R to suppress appetite. In monogenic obesities caused by loss-of-function variants upstream of the receptor — in POMC, PCSK1 or the leptin receptor — that signal never arrives, but MC4R itself remains intact and responsive. Setmelanotide restores the missing signal by activating the receptor directly. It therefore works only where the defect lies upstream, which is why its approved use is defined by genetic diagnosis rather than by obesity itself.
Origin
Synthetic cyclic peptide MC4R agonist.
Targets
Studies
- Setmelanotide for the Treatment of Acquired Hypothalamic Obesity
- Could setmelanotide be the game-changer for acquired hypothalamic obesity?
- Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period
- Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial
- 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
Research statistics
129 PubMed publications · 35.7% human clinical research · 26 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research status
Setmelanotide is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.
| FDA status | Approved |
|---|---|
| Availability | Prescription-Only |
| WADA (sport) | Permitted |
| Library classification | FDA-Approved |
How FDA approval, compounding and research-only status differ
Benefits
Setmelanotide side effects
The effects below are drawn from Setmelanotide's prescribing information, which lists the full adverse-reaction data.
Side Effects
- Hyperpigmentation
- Nausea
- Sexual-arousal disturbances
- Injection reactions
Storage & stability
This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.
Setmelanotide: frequently asked questions
What is Setmelanotide?
FDA-approved MC4R agonist (Imcivree) for rare genetic obesities (POMC, PCSK1, LEPR deficiency, Bardet-Biedl). Daily SC injection, not a general-obesity drug.
How does Setmelanotide work?
Setmelanotide is a cyclic peptide agonist selective for the melanocortin-4 receptor. MC4R sits at the bottom of the leptin-melanocortin pathway: leptin signals adiposity to the hypothalamus, POMC neurons release alpha-MSH, and alpha-MSH acts at MC4R to suppress appetite.
Is Setmelanotide FDA approved?
Yes. Setmelanotide is approved by the FDA, and approved products are prescription medicines. Approval is always for specific indications studied in clinical trials, so an approved status does not mean the compound is approved for every use it is discussed for. Research-chemical material sold under the same name is not the approved product.
What is the half-life of Setmelanotide?
Reported half-life for Setmelanotide is ~11 hours. Half-life describes how long the compound persists in circulation, not how long any effect lasts, and published figures vary with route of administration, formulation and the population studied.
Is Setmelanotide banned in sport?
Setmelanotide is recorded here as permitted in sport. Anti-doping status is revised annually, so athletes subject to testing should confirm against the current WADA Prohibited List before use.
What peptides are similar to Setmelanotide?
Compounds most often compared with Setmelanotide include Melanotan II, Afamelanotide, Bremelanotide and KPV. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- FDA label — ImcivreeExternal reference
- Setmelanotide for the Treatment of Acquired Hypothalamic Obesity — N Engl J Med, 2026External reference
- Could setmelanotide be the game-changer for acquired hypothalamic obesity? — Front Endocrinol (Lausanne), 2023External reference
- Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period — Lancet Diabetes Endocrinol, 2022External reference
- Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial — Lancet Diabetes Endocrinol, 2024External reference
- 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 — Lancet Diabetes Endocrinol, 2020External reference
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Sep 6, 2026 · Version 2
This Setmelanotide profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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