Setmelanotide (Imcivree)
A weight-loss drug for rare genetic forms of obesity. An MC4R agonist, FDA-approved in 2020 for obesity due to POMC, PCSK1, or LEPR deficiency and in 2022 for Bardet-Biedl syndrome; it's the educational anchor for melanocortin-pathway weight regulation.
Setmelanotide (Imcivree): A weight-loss drug for rare genetic forms of obesity. An MC4R agonist, FDA-approved in 2020 for obesity due to POMC, PCSK1, or LEPR deficiency and in 2022 for Bardet-Biedl syndrome; it's the educational anchor for melanocortin-pathway weight regulation. Setmelanotide (sold as Imcivree) is an FDA-approved drug for a very specific kind of obesity, caused by rare genetic mutations in the leptin/melanocortin pathway.
Setmelanotide (sold as Imcivree) is an FDA-approved drug for a very specific kind of obesity, caused by rare genetic mutations in the leptin/melanocortin pathway. It activates MC4R, the same melanocortin receptor MT-1, MT-2 and PT-141 hit. Educational reference for how the melanocortin pathway controls weight.
Approved as Imcivree (2020) for obesity due to POMC, PCSK1, or LEPR deficiency. 2022 expansion: Bardet-Biedl syndrome.
FDA-approved drug products containing this substance are available. Compounded versions are not FDA-approved.
Yes, pediatric endocrinology and metabolic-disease specialists prescribe for the genetic-obesity indications.
Who it's for
- βPatients with diagnosed monogenic obesity (POMC, PCSK1, LEPR, BBS)
- βEducational reference for the MC4R pathway
- βResearchers studying the melanocortin / hypothalamic appetite axis
What to expect
- Week 1
Appetite drops noticeably in monogenic-obesity patients. Skin pigmentation begins to shift.
- Week 4
Weight loss tracking established.
- Week 8
Cumulative weight loss; pigmentation visible.
Looking at Setmelanotide (Imcivree)? Your next 3 steps
- 1Work out your syringe units
Vial size + BAC water turns into the exact units to draw for Setmelanotide (Imcivree).
Open calculator β - 2See what to stack & monitor
The companion supplements and the bloodwork worth tracking on this kind of protocol.
Bloodwork guide β - 3Save it & ask the Coach
A free account gets you Coach questions every day, free; membership saves your stack and makes the Coach stack-aware.
Create free account β
How it works (mechanism)
Selective MC4R agonist. Activates the melanocortin-4 receptor in the hypothalamus, the appetite-control hub. In patients with rare loss-of-function mutations in this pathway, restoring the signal restores appetite regulation.
Dosing protocol
Stacks well with
Side effects
When NOT to use
- β Active depression or suicidal ideation
- β Pregnancy / nursing
Bloodwork to monitor
- β’ Skin / mole monitoring (dermatology)
- β’ Mental-health screening
Common mistakes
- β’ Using it for general obesity (it's specific to monogenic obesity)
- β’ Skipping the mole-map baseline (pigmentation drift is real)
- β’ Underestimating the depression / suicidal-ideation monitoring requirement
What it actually is
Setmelanotide, sold as Imcivree, is an approved daily injection for a very specific problem: obesity caused by a broken gene in the brain's appetite pathway. FDA approved it in 2020 for POMC, PCSK1 and LEPR deficiency and in 2022 for Bardet-Biedl syndrome. It is on this page as the anchor for understanding melanocortin-pathway weight regulation, not as a general obesity drug β for common obesity it is not indicated and there is no evidence it works.
Leptin, released by fat tissue, signals fullness to the hypothalamus. That signal passes through POMC neurons and then the MC4 receptor. If any link in that chain is genetically broken, the brain never receives a satiety signal no matter how much fat tissue exists, and the result is relentless hunger from early childhood. Setmelanotide is an MC4R agonist: it supplies the downstream signal directly, bypassing the broken upstream link. That is why it transforms outcomes for those specific genotypes and does nothing for obesity where the pathway is intact.
Forms, and which is which
Daily subcutaneous injection, titrated, dispensed on prescription after genetic confirmation.
Verdict: The only form, and it requires a diagnosis.
Sold to people without the genotype it treats, for a use with no supporting evidence, at a compound whose side effect profile includes mood effects requiring monitoring.
Verdict: Wrong drug for the wrong problem, unverified.
Same receptor family, different selectivity. The pigmentation side effect setmelanotide shares with them comes from off-target MC1R activity.
Verdict: Related chemistry, entirely different purpose.
No approved oral form.
Verdict: No approved oral form exists.
What it is claimed to do, graded
The approved indication, on phase 3 evidence. The effect in these genotypes is large in a way general obesity drugs are not.
Approved in 2022 on a randomised trial published in Lancet Diabetes and Endocrinology.
Hunger scores are a trial endpoint and improve alongside weight. For people who have never experienced satiety, this is often the outcome that matters most.
A phase 2 open-label trial in 2024 reported benefit. Open-label and early.
It is not indicated for this and the mechanism argues against it: if the melanocortin pathway is intact, supplying more downstream signal is not the missing piece.
Grades describe how much human evidence exists for that specific claim, not whether it will work for you or whether it is safe.
Pros and cons
- β’ Approved, with phase 3 evidence in the genotypes it treats
- β’ Addresses a cause rather than a symptom, which almost no obesity drug does
- β’ For the right patient the effect on hunger is life-changing
- β’ Prescribing information, monitoring requirements and interactions are properly documented
- β’ Only relevant to rare genetic diagnoses, confirmed by testing
- β’ Skin hyperpigmentation affects around 60% of patients, from off-target MC1R activity
- β’ Depression and suicidal ideation are labelled warnings requiring active mood monitoring
- β’ Spontaneous erections are a common effect in males, from the same receptor family that makes MT-2 do it
- β’ Very expensive, and daily injection
When to stop
- β’ New or worsening depression, or any thoughts of self-harm β this is a labelled warning, act on it
- β’ Any mole changing size, shape, colour or border
- β’ Persistent nausea or vomiting
- β’ No response after an adequate trial in a confirmed genotype
Interactions
Mood effects are a labelled warning and require monitoring. Starting it into active depression is the wrong direction.
Overlapping receptor family. Compounds pigmentation and other melanocortin effects.
The drug darkens skin and existing moles, which interferes with the visual monitoring melanoma detection relies on.
Not a pharmacokinetic interaction, but mood is the thing being watched on this drug.
Not an interaction. It is the precondition β without the genotype there is no reason to expect a response.
Is this for you?
- β’ People with a genetically confirmed POMC, PCSK1 or LEPR deficiency, or Bardet-Biedl syndrome, under specialist care
- β’ Anyone reading this to understand how the melanocortin pathway regulates appetite
- β’ You have common obesity without one of these genetic diagnoses
- β’ You have active depression or suicidal ideation
- β’ You have a history of melanoma or atypical moles
- β’ You are pregnant or nursing
The one number
Sources for the claims above
- First approval and regulatory basis
- Efficacy and safety in Bardet-Biedl syndrome
- Phase 2 open-label trial in acquired hypothalamic obesity
Drug & supplement interactions
- β MAO inhibitors: theoretical interaction (not contraindicated, but disclose)
- β Drugs causing depression: caution, Imcivree carries a depression / suicidal-ideation warning (monitor mood)
- β MC4R activation: spontaneous erections in male patients
Community patterns
New to Setmelanotide (Imcivree)? Grab the starter checklist.
Drop your email and we'll send the one-page starter checklist beginners actually need first. No account needed.
No spam, and we never sell your email. Just the checklist. Email support@pepdex.co to opt out any time.
Numbers redacted in this preview. Members get the full answer, on their own stack.
Ask the Coach anything about Setmelanotide (Imcivree) or your own stack. This is it working.
Trained only on Pepdex content. Does the dose math, flags interactions, knows your stack. Won't push vendors, won't pretend to be a doctor.
Unlock the full Coach, from $4.99/week βFrequently asked
What is Setmelanotide (Imcivree)?+
Is Setmelanotide (Imcivree) FDA approved?+
Is Setmelanotide (Imcivree) legal?+
Is Setmelanotide (Imcivree) banned by WADA?+
Are you still natty after taking Setmelanotide (Imcivree)?+
Do doctors prescribe Setmelanotide (Imcivree)?+
What's the typical dose of Setmelanotide (Imcivree)?+
What are the side effects of Setmelanotide (Imcivree)?+
How long until Setmelanotide (Imcivree) starts working?+
What can you stack with Setmelanotide (Imcivree)?+
Where do people get Setmelanotide (Imcivree)?+
Common questions about Setmelanotide (Imcivree)
Tracked alongside Setmelanotide (Imcivree)
Same goal, different aisle β each graded on its own evidence in the Pepdex catalog.
More in Fat Loss
Strong weight loss with a cleaner side effect profile than semaglutide. A dual agonist (GLP-1 + GIP), FDA-approved as Mounjaro / Zepbound.
The original weight-loss wave, sold as Ozempic / Wegovy. A GLP-1 agonist.
Triple agonist (GLP-1 + GIP + glucagon) from Eli Lilly. In trials it outperforms Tirzepatide for weight loss.
Daily GLP-1 receptor agonist. FDA-approved 2010 (Victoza, T2D) and 2014 (Saxenda, obesity). The first wave of modern GLP-1 weight-loss therapy and direct predecessor to Semaglutide.