Scientific context only. Not medical advice, not a recommendation to use.
At a glance
Setmelanotide (brand name Imcivree) is a synthetic cyclic octapeptide and an agonist at the melanocortin-4 receptor (MC4R). It was developed and approved as a prescription medicine for chronic weight management in rare genetic forms of obesity within the MC4R signalling pathway (including POMC, PCSK1 and LEPR deficiency as well as Bardet-Biedl syndrome). The following information is provided for informational and educational purposes only.
Researched for
Obesity due to POMC deficiencyObesity due to PCSK1 deficiencyObesity due to leptin receptor (LEPR) deficiencyObesity associated with Bardet-Biedl syndromeRegulation of hunger (hyperphagia) within the MC4R signalling pathway
Official status
US: Prescription
Approved by the US FDA on 25 November 2020 under the brand name Imcivree for chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency; later expansions include Bardet-Biedl syndrome. Prescription-only.
Setmelanotide is an agonist at the melanocortin-4 receptor (MC4R), a central receptor of the hypothalamic melanocortin pathway involved in the control of energy balance, satiety and body weight. In certain genetic defects (e.g. in POMC, PCSK1 or LEPR), the natural activation of MC4R is reduced. Setmelanotide activates MC4R directly, thereby bypassing the upstream defect. This description is mechanistic and neutral and does not constitute a recommendation for use.
02
Evidence at a glance
Reading note. The distribution shows on which evidence tier each observation sits. Strong colours mark stronger evidence — weaker tiers are deliberately visible, not hidden.
3 observations · 2 tiers
Human RCT
1
Human trial
2
03
What the studies show
Human trial
Mensch
Clément K. et al. 2020
In single-arm, open-label phase 3 trials, a reduction in body weight was observed in individuals with severe obesity due to POMC or LEPR deficiency.
What does NOT follow: These studies were single-arm and open-label (no placebo control) and limited to rare genetic subgroups. This does NOT imply transferability to general obesity and is not a recommendation for use.
Human RCT
Mensch
Haqq AM. et al. 2022
In a randomised, placebo-controlled phase 3 trial in Bardet-Biedl syndrome, a reduction in body weight compared with placebo was observed.
What does NOT follow: The study involved a small, specific patient group (Bardet-Biedl/Alström syndrome). The results are not transferable to other populations and do not constitute an instruction for use.
Human trial
Mensch
Kühnen P. et al. 2016
In early human observations in POMC deficiency, a reduction in reported hunger (hyperphagia) was documented.
What does NOT follow: This was a very small, open-label investigation of individual cases. Single-case observations do not allow general conclusions and are not a recommendation for use.
04
Where studies disagree
Open question
How serious is the pigment and nevus risk of melanocortin activation?
POSITION A
The hyperpigmentation is mostly cosmetic and reverses after discontinuation.
POSITION B
The label lists darkening and the appearance of new melanocytic nevi as adverse reactions — dermatologically relevant for a melanocortin agonist.
CURRENT STATE · Regular skin checks are advised; a long-term melanoma risk is not conclusively resolved.
05
Pharmacokinetics
Theoretical concentration curve at a half-life of 11 h. Pure pharmacokinetic model — not a dosing recommendation.
Which routes of administration the available studies describe — neutral reporting, not a usage guide.
Subcutaneous
In the underlying trial and regulatory literature, setmelanotide is described as a subcutaneously administered peptide. This statement is purely descriptive and contains no dosing or usage instructions.
06d
Safer use & risks
Risk notes for harm reduction — descriptive, not a usage or dosing guide.
⚠ Important — please read
This platform does NOT provide usage or dosing instructions. The points below describe risks and are meant to help avoid harm — they do not replace medical advice. Anyone who uses a substance should discuss it with a doctor.
This substance is approved (in at least one country) — use belongs in medical hands, within the approved indication and a physician-set dose.
Online numbers are not a benchmark
Amounts from TikTok, YouTube and forums are mostly imitation rather than data — and are often wrongly derived from animal studies (µg/kg). Not a reliable benchmark for humans.
Sterility & infection risk
Injection solutions prepared or stored non-sterile carry an infection and abscess risk. Contamination is common with grey-market product.
Unknown product quality
Research-/grey-market product is not quality-tested: identity, purity and actual content are often unknown, and counterfeits occur.
Mind interactions
Combinations with medications or pre-existing conditions can carry risks (see the Interactions section). Clarify with a doctor beforehand.
Warning signs — seek medical help
With persistent pain, redness/swelling at the injection site, fever, shortness of breath, racing heart, chest pain or allergic reactions, seek medical help immediately.
A doctor, not a forum
Concrete questions about use and amount belong in a conversation with a doctor — not in a comment thread.
07
Known adverse events from studies
Factual reporting of what studies observed. Not a safety statement for individual use.
Human trial
Injection-site reactions were reported in clinical trials.
Frequency figures derive from controlled study populations and are not readily transferable to individuals. This does not replace medical advice.
häufig in Studien berichtet
Human trial
Reversible skin hyperpigmentation was observed in connection with activation of melanocortin receptors.
This effect is related to the mechanism of action at the melanocortin system; the observation derives from study populations and does not constitute an individual risk assessment.
Human trial
Nausea and gastrointestinal complaints were documented in trials.
The data derive from small, specific study populations and do not allow general conclusions or individual predictions.
07b
Interactions & combinations
Documented interactions and contraindications from studies, prescribing information and guidelines. Where no data exists, this is stated.
Reporting of risks, NOT a combination guide. The absence of an entry does not mean „safe to combine“ but „not sufficiently studied“.
No documented interactions recorded
We have not yet found robustly documented interactions for this peptide. This does NOT mean none exist — the data is limited.
10
Anecdotal observations
Weakest evidence tier — not supported by studies
Reading note. This section gathers popular claims from communities and forums. They are explicitly marked as weakest-tier evidence. Unblinded self-reports are particularly prone to placebo, recall and confirmation biases.
Why no amounts or protocols are listed here. We deliberately show only WHAT communities report — not in what amount or how it is used. Anecdotal "doses" or "biohacker protocols" are neither verified nor standardised nor safe; publishing them would be a usage guide, which we do not provide on principle. Specific amounts belong in a conversation with a doctor, not in a forum.
As with other melanocortin agonists (Melanotan II, PT-141), skin darkening and changes to moles are described.
expected class-effect profile
Not supported by studies: For setmelanotide this is listed as an adverse reaction in the label (including darkening and new appearance of nevi); regular dermatological monitoring is documented as advised.
10b
What online communities discuss
Recurring themes from Reddit, Quora and patient forums — synthetically summarised, sources linked. Not scientific evidence, but a signal of what users report. Deliberately separated from the study base.
Non-scientific sources. What users report in forums — synthetically summarised, paraphrased, with link to source. Not validated by studies.
On drugs.com, setmelanotide (Imcivree) is rated predominantly positively (around 7.5 out of 10). As the profile of a melanocortin (MC4R) agonist, skin darkening, darkening of existing moles and the appearance of new melanocytic nevi stand out, alongside nausea, headache, injection-site reactions, spontaneous erections and warnings about depressed mood.
What this does NOT mean:Review platforms are self-selected, unblinded and not representative; the figures are a snapshot (as of June 2026). They do not replace controlled data — see the studies section. The pigment and nevus effects are shared mechanistically with Melanotan II and PT-141 (all melanocortin agonists); dermatological monitoring is advised in the label.
Approved by the US FDA on 25 November 2020 under the brand name Imcivree for chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency; later expansions include Bardet-Biedl syndrome. Prescription-only.
2026-06-07
EU
Prescription
The European Commission granted an EU-wide marketing authorisation for Imcivree (setmelanotide) on 16 July 2021, following the EMA's recommendation. Prescription-only.
2026-06-07
Germany
Prescription
In Germany, prescription-only on the basis of the centralised EU authorisation (European Commission/EMA, 16 July 2021). The approved indications for rare genetic forms of obesity apply.
2026-06-07
12
Reconstitution calculator
Pure mg/mL maths — works like a calculator. Not a usage recommendation.
Peptides ship as a dry powder. Once dissolved in a liquid (reconstitution), this calculator answers a single question: how much substance is in one millilitre of solution afterwards?
1Enter the vial's substance amount (printed on the label).
2Enter how much solvent you add.
3Result = concentration in mg per mL.
Printed on the label
/
Liquid you add
=
2.50
mg / mL
5 mg in 2 mL gives 2.50 mg/mL — each millilitre contains 2.50 mg of substance.
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
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