Peptides / Weight and metabolic

Synthetic analog · 8 amino acids · 1,117.3 Da

Setmelanotide

ApprovedNot banned in sport

Setmelanotide (Imcivree) is a melanocortin-4 receptor agonist approved in the US and EU for certain genetic and hypothalamic forms of obesity. Studies in people tested it on weight, appetite, quality of life and skin pigmentation, and tracked side effects. PepBank shows 276 results on setmelanotide from 45 studies in people, and 56 from animal and lab studies. The strongest evidence is a randomized trial in people. Data as of 2026-10-30.

Also known as Imcivree

8 amino acids, from first to lastRCAHFRWC

Evidence level: Large trials in people276 of 332 results come from studies in people, including randomized trials.

Results in people

276

83% of 332 results

Results in animals

12% of 332 results

Results in lab cells

5% of 332 results

From computer models

0% of 332 results

Overview

Setmelanotide at a glance

What it is	Synthetic analog, 8 amino acids
Approval	Approved in the US and EU (Imcivree, 2020)
In sport	Not listed as banned by WADA
Studies	62 studies with results. 60 of them gave setmelanotide, with 332 results. 276 in people40 in animals16 in lab cells
Best study in people	Randomized controlled trial with 120 people (2026)
Clinical trials	25 registered: 5 active or planned, 14 with posted results
Community use	Long-term weight reduction and maintenance for acquired hypothalamic obesity, Bardet-Biedl syndrome, or label-defined POMC, PCSK1, or LEPR deficiency.

The science

What is setmelanotide?

Setmelanotide is a cyclic eight-residue melanocortin-4 receptor agonist.

Amino acids in one chain

The history of setmelanotide

2016
The oldest paper on setmelanotide in PepBank is from 2016.
2017February
A registered trial of setmelanotide started (NCT02896192).
2020November
FDA approved Imcivree for reduce excess body weight and maintain weight reduction long term. Includes acquired hypothalamic obesity from age 4 and Bardet-Biedl syndrome from age 2. Includes POMC, PCSK1, or LEPR deficiency from age 2 with pathogenic, likely pathogenic, or uncertain-significance variants confirmed by genetic testing.

Setmelanotide structure and chemistry

The key facts about the molecule. Long codes are in the closed section below.

Sequence, 8 amino acidsFrom the first amino acid to the last

+R1CAHF5+RWC

Darker means more water-repelling+ and − show charge in the bodyOutlined: changed amino acid

Structure

Setmelanotide is a synthetic analog of 8 amino acids, with a ring, 1 disulfide bond, 2 changed amino acids.

Formula

C₄₉H₆₈N₁₈O₉S₂

Molecular weight

1,117.3 g/mol

CAS number

920014-72-8

Target

Melanocortin 4 receptor (gene MC4R): agonistEvidence: Official prescribing information, mechanism of action

Development

Rhythm Pharmaceuticals. Highest phase: past the trial stage (see status).

Identifiers

PubChem 11993702, ChEMBL CHEMBL3301624, UNII N7T15V1FUY, DrugBank DB11700

Full sequence, SMILES and InChIKey

InChIKey
HDHDTKMUACZDAA-PHNIDTBTSA-N

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

See charge, composition and 3D structure on the Scientific page

The evidence

What setmelanotide studies show

Results grouped by what the studies measured. Each card shows where its results come from.

Large trials in people276 of 332 results come from studies in people, including randomized trials.

Weight and appetite

127 results · 107 in people · 20 animal

In acquired hypothalamic obesity, setmelanotide reduced BMI more than placebo at 52 weeks. The New England journal of medicine, 2026

Top results

In acquired hypothalamic obesity, setmelanotide reduced BMI more than placebo at 52 weeks. (The New England journal of medicine, 2026)
In participants aged at least 12 years, setmelanotide reduced hunger scores more than placebo. (The New England journal of medicine, 2026)
In BBS patients, setmelanotide treatment was linked to less body fat. (The Journal of clinical endocrinology and metabolism, 2026)

Daily life and fitness

24 results · 24 in people

In adults with Bardet-Biedl syndrome, quality-of-life scores increased from baseline after setmelanotide. Orphanet journal of rare diseases, 2023

Top results

In adults with Bardet-Biedl syndrome, quality-of-life scores increased from baseline after setmelanotide. (Orphanet journal of rare diseases, 2023)
In a child receiving setmelanotide, motor skills improved, including crawling and kneeling. (Obesity facts, 2026)
Among adults assessed at Week 52, 5 of 6 had meaningful quality-of-life improvement from baseline during setmelanotide. (Orphanet journal of rare diseases, 2022)

Skin, hair and wounds

21 results · 21 in people

Darker skin was among the most common adverse events during setmelanotide treatment in Smith-Magenis syndrome. Obesity research & clinical practice, 2024

Top results

Darker skin was among the most common adverse events during setmelanotide treatment in Smith-Magenis syndrome. (Obesity research & clinical practice, 2024)
Five participants with LEPR deficiency receiving setmelanotide reported treatment-related skin disorders. (The lancet. Diabetes & endocrinology, 2020)
Skin darkening was among the most common side effects in participants with Smith-Magenis syndrome who received setmelanotide. (Obesity research & clinical practice, 2024)

Heart and blood vessels

12 results · 10 in people · 2 animal

In BBS patients receiving setmelanotide, metabolic syndrome severity decreased compared with baseline at Week 52. The Journal of clinical endocrinology and metabolism, 2025

Top results

In BBS patients receiving setmelanotide, metabolic syndrome severity decreased compared with baseline at Week 52. (The Journal of clinical endocrinology and metabolism, 2025)
In a child with hypothalamic obesity, weight, liver tests, lipids, movement, interaction and quality of life improved during setmelanotide treatment. (Frontiers in endocrinology, 2026)
In POMC or LEPR deficiency, most patients improved in at least one metabolic measure compared with baseline during setmelanotide treatment. (The Journal of clinical endocrinology and metabolism, 2026)

Cholesterol and blood fats

8 results · 7 in people · 1 animal

In Smith-Magenis syndrome, total cholesterol decreased during setmelanotide treatment. Obesity research & clinical practice, 2024

Top results

In Smith-Magenis syndrome, total cholesterol decreased during setmelanotide treatment. (Obesity research & clinical practice, 2024)
In people with Smith-Magenis syndrome, total cholesterol decreased during setmelanotide treatment. (Obesity research & clinical practice, 2024)
In a patient with atypical lipodystrophy, high triglycerides did not improve from before setmelanotide treatment. (Endocrinology, diabetes & metabolism case reports, 2020)

Liver

7 results · 7 in people

In BBS patients, setmelanotide treatment was linked to a lower liver attenuation imaging value. The Journal of clinical endocrinology and metabolism, 2026

Top results

In BBS patients, setmelanotide treatment was linked to a lower liver attenuation imaging value. (The Journal of clinical endocrinology and metabolism, 2026)
In a man with BBS, liver enzyme levels became normal during setmelanotide treatment after liraglutide stopped. (Nephron, 2026)
In a boy with ROHHAD syndrome, liver fat decreased during setmelanotide treatment. (Pediatrics, 2026)

All 62 setmelanotide studies by area Open the Scientific page

Key setmelanotide studies

Studies in people come first, then studies in animals and in the lab.

People
Setmelanotide for the Treatment of Acquired Hypothalamic Obesity
Miller et al. 2026 · The New England journal of medicine · 120 people · cited by 7
8 results
People
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
Clément et al. 2020 · The lancet. Diabetes & endocrinology · 21 people · cited by 363
12 results
People
Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial
Roth et al. 2024 · The lancet. Diabetes & endocrinology · 18 people · cited by 62
11 results
People
A Phase 3 Trial in Participants With Obesity Due to Bardet-Biedl Syndrome or Alström Syndrome: Efficacy and Safety of the Melanocortin 4 Receptor Agonist Setmelanotide
Haws et al. 2021 · Journal of the Endocrine Society · 14 people · cited by 0
5 results
People
Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial
Argente et al. 2025 · The lancet. Diabetes & endocrinology · 12 people · cited by 33
16 results

All 62 Setmelanotide studies

Setmelanotide clinical trials

ClinicalTrials.gov lists 25 trials of setmelanotide. 5 are active or planned, and 14 have posted results. PepBank does not show trial results.

Solid bars are dates that happened. Hatched bars are planned dates. Data from ClinicalTrials.gov.

Long Term Extension Trial of Setmelanotide

Phase 2/3completed205 people

A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Phase 3active, not recruiting143 planned

Study of Setmelanotide Effects on QTc (Corrected QT) Interval in Healthy Participants

Phase 4completed77 people

All 15 Setmelanotide trials

Status and safety

Is setmelanotide approved?

FDA

United States

Approved

An approved medicine contains it.

EMA

European Union

Approved

An approved medicine contains it.

WADA

Sport

Not banned

Not on the 2026 Prohibited List.

Yes. Approved in the US and EU (Imcivree, 2020). The FDA label for Imcivree says: “Reduce excess body weight and maintain weight reduction long term” Not listed as banned by WADA.

Laws and labels change, so check the regulator for the current status.

Setmelanotide side effects and safety

PepBank has 91 safety results from studies of setmelanotide. 91 of them come from studies in people.

Safety results from studies (91)

In acquired hypothalamic obesity, adverse events occurred more often with setmelanotide than placebo. (The New England journal of medicine, 2026)
All participants with Smith-Magenis syndrome reported adverse events during setmelanotide treatment. (Obesity research & clinical practice, 2024)
No participants with Smith-Magenis syndrome stopped setmelanotide because of side effects. (Obesity research & clinical practice, 2024)
All participants with BBS reported an adverse event during setmelanotide treatment. (Diabetes, obesity & metabolism, 2020)
All patients with these genetic deficiencies experienced at least one adverse event during setmelanotide treatment. (Journal of the Endocrine Society, 2021)
No serious treatment-related adverse events occurred in either setmelanotide trial in POMC or LEPR deficiency obesity. (The lancet. Diabetes & endocrinology, 2020)
Nausea occurred in 61% of patients with hypothalamic obesity receiving setmelanotide. (The lancet. Diabetes & endocrinology, 2024)
In children aged 2-5 years receiving setmelanotide, all adverse events were mild or moderate. (The lancet. Diabetes & endocrinology, 2025)
In patients with POMC or LEPR deficiency, skin pigmentation increased from before setmelanotide treatment. (Skin pharmacology and physiology, 2021)
No new safety concerns emerged during extended setmelanotide treatment in patients with heterozygous POMC, PCSK1 or LEPR variants. (Journal of the Endocrine Society, 2022)
In patients with SRC1 variant obesity, no new safety concerns emerged during long-term setmelanotide treatment. (Journal of the Endocrine Society, 2022)
No patients with SH2B1 genetic obesity stopped setmelanotide due to adverse events during the extension. (Journal of the Endocrine Society, 2022)
In patients with these genetic deficiencies, long-term setmelanotide was generally well tolerated. (Journal of the Endocrine Society, 2022)
The setmelanotide obesity cohort showed no new safety signals compared with the phase 3 safety profile. (Obesity, 2025)
In adverse event reports, setmelanotide was linked to disproportionately frequent reports of darker skin. (Clinical, cosmetic and investigational dermatology, 2025)
In patients with BBS, no new safety signals were observed during long-term setmelanotide treatment. (Journal of the Endocrine Society, 2022)
In prepubertal children with LEPR or POMC deficiency, setmelanotide was generally well tolerated. (European journal of endocrinology, 2025)
In young adults receiving setmelanotide, adverse effects were mild and did not limit treatment. (Journal of endocrinological investigation, 2026)
In two children with BBS after kidney transplantation, graft function remained stable during setmelanotide treatment. (International journal of molecular sciences, 2026)
In a boy receiving setmelanotide, no major side effects were reported except skin darkening and temporary spontaneous erections. (JCEM case reports, 2023)
A woman with a PCSK1 variant developed severe skin darkening with setmelanotide. (Obesity, 2026)
A child receiving setmelanotide developed skin rash. (Obesity facts, 2026)
A boy with LEPR deficiency developed darker skin shortly after starting setmelanotide. (Journal of clinical research in pediatric endocrinology, 2025)
In acquired hypothalamic obesity, serious adverse events occurred more often with setmelanotide than placebo. (The New England journal of medicine, 2026)

See every safety result on the Scientific page

Doses studied (16 shown)

The doses that these studies used. They are not recommendations.

Dose as reported	Class	Species	Route	Duration	Design	Source
1.5 to 3.0 mg once daily	Human	human	subcutaneous	52 weeks after dose escalation	Randomized trial in people · n = 120	Miller 2026
Titrated to 3·0 mg once daily	Human	human	subcutaneous	16 weeks	Trial in people without random groups · n = 18	Roth 2024
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum	Human	human	subcutaneous	52 weeks	Trial in people without random groups · n = 12	Argente 2025
Titrated to maximum 3 mg once daily	Human	human	injection	3 months at full dose	Trial in people without random groups · n = 12	Lazareva 2024
titrated to a maximum of 3mg	Human	human	injection	3mo at full dose	Trial in people without random groups · n = 12	Lazareva 2024
≤3 mg once daily, individually titrated	Human	human	Not reported	Not reported	Trial in people without random groups · n = 8	Haws 2020
0.25 to 3.0 mg daily	Human	human	Not reported	Not reported	Trial in people without random groups · n = 35	Clément 2021
0.3-0.5 mg/day in POMC deficiency; 2.5 mg/day in LEPR deficiency	Human	human	Not reported	Not reported	Observational study	Kahveci 2025
0.5 mg daily	Human	human	Not reported	12 months	Reports of single patients · n = 1	Dubern 2023
3 mg/day	Human	human	Not reported	Not reported	Reports of single patients · n = 1	Kondou 2026
0.25 mg daily titrated to 1.5 mg	Human	human	Not reported	13 months	Reports of single patients · n = 1	Dauleh 2026
≥1.25 mg daily	Human	human	Not reported	Not reported	Reports of single patients · n = 1	Dauleh 2026
0.5 mg/day increased to 2.5 mg/day in 0.5 mg increments	Human	human	subcutaneous	Not reported	Reports of single patients · n = 1	Pons 2026
2 mg daily titrated to 3 mg	Human	human	Not reported	Not reported	Reports of single patients · n = 1	Haggerty 2025
1 mg/kg daily	Animal	mouse	Not reported	Ten days	Study in live animals	Rivera 2025
0.2 mg/kg daily	Animal	mouse	Not reported	Ten days	Study in live animals	Rivera 2025

From the community

How people use it

What people report online. It comes from forums and guides, not from studies.

Community-reported. Not tested in trials.

This record describes one US label maintenance regimen for Imcivree injection. It does not describe unsupervised community dosing.

Reported routines and cautions

What people use it for

Long-term weight reduction and maintenance for acquired hypothalamic obesity, Bardet-Biedl syndrome, or label-defined POMC, PCSK1, or LEPR deficiency.S1

Reported regimens

Regimens that community sources report for Setmelanotide. Community-reported, not tested in trials.
Context	Route	Amount	How often	How long	Agreement	Sources
Imcivree 10 mg/mL injection for adults and children aged 6 years or older with a labeled indication. This selected regimen covers normal kidney function or mild or moderate renal impairment.Official label dosing of an approved product	subcutaneous injectionInject into the abdomen, thigh, or arm. Rotate the site each day. Do not inject intravenously or intramuscularly.	3 mg per dose	once daily, at the beginning of the day, without regard to meals	Not stated	Single official US label source.	S1

Cautions

The label contraindicates use after a serious hypersensitivity reaction to setmelanotide or its excipients. Serious reactions include anaphylaxis.S1
The label warns about depression, suicidal thoughts, sexual adverse reactions, prolonged erections, skin hyperpigmentation, and new or darkening nevi. It requires skin examinations before treatment and periodically during treatment.S1
Patients with acquired hypothalamic obesity need monitoring for acute adrenal insufficiency. Those with central diabetes insipidus also need sodium monitoring.S1
The label does not recommend use during breastfeeding. Pregnancy needs the assessment described in the full label.S1

Status notes

Imcivree has US approval and EU authorisation for specific obesity conditions. US and EU genetic diagnostic criteria differ. Neither indication covers general obesity.S1 S2

Community sources

S1Imcivree US prescribing information (opens in a new tab)dailymed.nlm.nih.gov
S2EMA regulatory information (opens in a new tab)ema.europa.eu

Gaps

No independent community regimen is included. This record covers one selected US label maintenance regimen. Starting doses, titration schedules, tolerance adjustments, younger patient groups, and severe renal impairment require the full label. The selected regimen does not specify a fixed treatment duration.

Questions and more

Ask a question about setmelanotide

The answer links to every study it uses.

What does the evidence say about setmelanotide?Is setmelanotide tested in people?Compare with Liraglutide Compare with Semaglutide

Sources

Database: PepBank data for setmelanotide (data version 308560)
Regulator: FDA status record
Regulator: EMA status record
Regulator: WADA status record
Trial registry: ClinicalTrials.gov
Community: community sources (forums and guides), as summarized in the PepBank community file

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

PepBank is a research reference. Talk to a doctor before you use any peptide.

Ask your AI about setmelanotide

Setmelanotide

ApprovedNot banned in sport

Also known as Imcivree

What it is

Synthetic analog, 8 amino acids

Approval

Approved in the US and EU (Imcivree, 2020)

In sport

Not listed as banned by WADA

Studies

62 studies with results. 60 of them gave setmelanotide, with 332 results.
276 in people40 in animals16 in lab cells

Best study in people

Randomized controlled trial with 120 people (2026)

Clinical trials

25 registered: 5 active or planned, 14 with posted results

Community use

Long-term weight reduction and maintenance for acquired hypothalamic obesity, Bardet-Biedl syndrome, or label-defined POMC, PCSK1, or LEPR deficiency.

Dose as reported

Class

Species

Route

Duration

Design

Source

1.5 to 3.0 mg once daily

Human

human

subcutaneous

52 weeks after dose escalation

Randomized trial in people · n = 120

Miller 2026

Titrated to 3·0 mg once daily

Human

human

subcutaneous

16 weeks

Trial in people without random groups · n = 18

Roth 2024

Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum

Human

human

subcutaneous

52 weeks

Trial in people without random groups · n = 12

Argente 2025

Titrated to maximum 3 mg once daily

Human

human

injection

3 months at full dose

Trial in people without random groups · n = 12

Lazareva 2024

titrated to a maximum of 3mg

Human

human

injection

3mo at full dose

Trial in people without random groups · n = 12

Lazareva 2024

≤3 mg once daily, individually titrated

Human

human

Not reported

Trial in people without random groups · n = 8

Haws 2020

0.25 to 3.0 mg daily

Human

human

Not reported

Trial in people without random groups · n = 35

Clément 2021

0.3-0.5 mg/day in POMC deficiency; 2.5 mg/day in LEPR deficiency

Human

human

Not reported

Observational study

Kahveci 2025

0.5 mg daily

Human

human

Not reported

12 months

Reports of single patients · n = 1

Dubern 2023

3 mg/day

Human

human

Not reported

Reports of single patients · n = 1

Kondou 2026

0.25 mg daily titrated to 1.5 mg

Human

human

Not reported

13 months

Reports of single patients · n = 1

Dauleh 2026

≥1.25 mg daily

Human

human

Not reported

Reports of single patients · n = 1

Dauleh 2026

0.5 mg/day increased to 2.5 mg/day in 0.5 mg increments

Human

human

subcutaneous

Not reported

Reports of single patients · n = 1

Pons 2026

2 mg daily titrated to 3 mg

Human

human

Not reported

Reports of single patients · n = 1

Haggerty 2025

1 mg/kg daily

Animal

mouse

Not reported

Ten days

Study in live animals

Rivera 2025

0.2 mg/kg daily

Animal

mouse

Not reported

Ten days

Study in live animals

Rivera 2025

Context

Route

Amount

How often

How long

Agreement

Sources

Imcivree 10 mg/mL injection for adults and children aged 6 years or older with a labeled indication. This selected regimen covers normal kidney function or mild or moderate renal impairment.Official label dosing of an approved product

subcutaneous injectionInject into the abdomen, thigh, or arm. Rotate the site each day. Do not inject intravenously or intramuscularly.

3 mg per dose

once daily, at the beginning of the day, without regard to meals

Not stated

Single official US label source.

Setmelanotide

Setmelanotide at a glance

What is setmelanotide?

The history of setmelanotide

Setmelanotide structure and chemistry

What setmelanotide studies show

Weight and appetite

Daily life and fitness

Skin, hair and wounds

Heart and blood vessels

Cholesterol and blood fats

Liver

Key setmelanotide studies

Setmelanotide clinical trials

Is setmelanotide approved?

Setmelanotide side effects and safety

How people use it

What people use it for

Reported regimens

Cautions

Status notes

Community sources

Ask a question about setmelanotide

Related peptides

Sources

Setmelanotide

Setmelanotide at a glance

What is setmelanotide?

The history of setmelanotide

Setmelanotide structure and chemistry

What setmelanotide studies show

Weight and appetite

Daily life and fitness

Skin, hair and wounds

Heart and blood vessels

Cholesterol and blood fats

Liver

Key setmelanotide studies

Setmelanotide clinical trials

Is setmelanotide approved?

Setmelanotide side effects and safety

How people use it

What people use it for

Reported regimens

Cautions

Status notes

Community sources

Ask a question about setmelanotide

Related peptides

Sources