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Setmelanotide Guide & Dosage Chart

An MC4R agonist studied for genetic obesity.

Also known asImcivree
Routesubcutaneous
Setmelanotide — Dosage chart
Every row cited
GoalDoseFrequencyDurationEvidenceSource
Treatment of severe obesity due to LEPR or POMC deficiency (MC4R agonist therapy) 2–3 mg 1x/day per trial Clinical PMID 33137293
For research and educational use only. Not medical advice.

What is Setmelanotide?

Setmelanotide — sold under the brand name Imcivree — is a research peptide that targets a brain receptor called MC4R (melanocortin-4 receptor). It was developed specifically for people whose obesity is caused by rare genetic faults in a weight-control pathway in the brain.[4] In 2020, it became the first drug of its kind approved in the United States for chronic weight management in patients aged 6 and older with certain genetic mutations affecting that pathway.[4] On this page, however, we discuss it strictly as a research compound. Nothing here is medical advice.

How Setmelanotide Works

Think of the brain's weight-control system as a thermostat. Normally, a hormone called leptin sends a signal up through a chain of proteins — including one called POMC — and that signal eventually flips a switch at MC4R, telling your body to stop eating and burn energy. In people with certain genetic mutations, part of that chain is broken, so the switch never gets flipped. The result is extreme, relentless hunger and severe obesity from a very young age.[2]

Setmelanotide skips the broken parts of the chain and goes straight to the MC4R switch, activating it directly. It acts as an agonist — meaning it mimics and triggers the receptor the same way the natural signal would, if only the pathway were working properly.[1] By restoring that signal, the compound has been shown in research settings to reduce hunger and promote significant weight loss in people who carry these genetic defects.[1]

What the Research Shows

The strongest evidence comes from phase 3 clinical trials in patients with rare genetic obesity.

POMC and LEPR Deficiency

A landmark phase 3 trial enrolled patients with obesity caused by defects in either the POMC gene or the leptin receptor (LEPR) gene. After roughly one year of treatment, 80% of POMC-deficiency participants and 45% of LEPR-deficiency participants lost at least 10% of their body weight. Hunger scores dropped dramatically too — by about 27% in the POMC group and 44% in the LEPR group.[1] The most common side effects were injection-site reactions, skin darkening (hyperpigmentation), nausea, and vomiting. No serious treatment-related adverse events occurred in either trial.[1]

Bardet-Biedl and Alström Syndromes

A separate multicentre, randomised, double-blind, placebo-controlled phase 3 trial looked at two other rare genetic conditions — Bardet-Biedl syndrome (BBS) and Alström syndrome — both of which involve impaired signalling in the MC4R pathway and cause severe early-onset obesity.[5] Setmelanotide again produced meaningful weight loss and hunger reduction compared with placebo in this population.[5]

Acquired Hypothalamic Obesity

Researchers have also explored setmelanotide for acquired hypothalamic obesity — weight gain caused by brain tumour treatment that damages the hypothalamus rather than by a genetic mutation. A phase 2 open-label trial published in 2024 examined this use, expanding the potential research scope of the compound beyond purely inherited conditions.[6]

Context Among Obesity Treatments

Broader obesity treatment reviews note that highly targeted agents like setmelanotide are especially relevant where the root cause is a specific pathway defect, complementing the wider landscape of anti-obesity medications that are now becoming available.[3]

What Setmelanotide Is Being Studied For

  • POMC-deficiency obesity (genetic)[1]
  • Leptin receptor (LEPR) deficiency obesity (genetic)[1]
  • PCSK1 deficiency obesity (genetic)[4]
  • Bardet-Biedl syndrome (BBS)[5]
  • Alström syndrome[5]
  • Acquired hypothalamic obesity (from brain tumour treatment)[6]
  • Other rare MC4R-pathway deficiency disorders[4]

How Setmelanotide Is Dosed in Research

Setmelanotide is administered as a subcutaneous injection (under the skin, typically in the abdomen) once daily.[4] Doses are titrated upward gradually — starting low and increasing over several weeks — to balance efficacy with tolerability.[1] Because precise amounts depend on body weight, age, and the specific genetic condition being studied, researchers rely on structured dosing protocols. See the dosage chart on this page for a reference breakdown of the doses used in published trials, and use the calculator to explore weight-based adjustments for research planning purposes. This information is for research reference only and does not constitute prescribing guidance.

Mixing and Storing Setmelanotide

In clinical research, setmelanotide is supplied as a ready-to-inject solution in a multi-dose vial — it does not require the powder-reconstitution step common to many other research peptides.[4] For storage, the unopened vial should be kept refrigerated (typically 2–8 °C / 36–46 °F) and protected from light. Once in use, vials are generally kept refrigerated and used within the period specified in the study protocol. As with all injectable research compounds, sterile technique is essential: use a new syringe and needle for each injection, inspect the solution for particles or discoloration before use, and discard if anything looks unusual. Detailed handling instructions for any specific research batch should always follow the manufacturer's or study protocol's guidelines.

Sources

  1. 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. — The lancet. Diabetes & endocrinology, 2020. PMID 33137293.
  2. Current Treatments for Patients with Genetic Obesity. — Journal of clinical research in pediatric endocrinology, 2023. PMID 37191347.
  3. Approach to Obesity Treatment in Primary Care: A Review. — JAMA internal medicine, 2024. PMID 38466272.
  4. Setmelanotide: First Approval. — Drugs, 2021. PMID 33638809.
  5. 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. — The lancet. Diabetes & endocrinology, 2022. PMID 36356613.
  6. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. — The lancet. Diabetes & endocrinology, 2024. PMID 38697184.

Setmelanotide FAQ

What is Setmelanotide?
Setmelanotide (brand name Imcivree) is a peptide that directly activates the MC4R receptor in the brain — a key switch in the body's hunger and energy-balance system. It was developed for rare genetic forms of severe obesity where that system is broken due to mutations in genes like POMC or LEPR.[4] It is studied as a research compound and, in approved clinical settings, as a prescription treatment for specific genetic conditions.[1]
How does Setmelanotide work?
It works by bypassing broken steps in the brain's leptin-melanocortin pathway and stimulating the MC4R receptor directly. That receptor normally signals the body to reduce hunger and increase energy use. In people with genetic defects that disrupt the pathway upstream, setmelanotide restores that 'off' signal, reducing hyperphagia (extreme hunger) and promoting weight loss.[1][2]
What is Setmelanotide used for in research?
Research has focused on several rare conditions: POMC deficiency, LEPR deficiency, PCSK1 deficiency, Bardet-Biedl syndrome, and Alström syndrome — all of which cause severe early-onset obesity via MC4R-pathway impairment.[4][5] Researchers are also investigating its potential in acquired hypothalamic obesity caused by brain tumour treatment.[6]
How is Setmelanotide dosed?
In published trials, setmelanotide is given as a once-daily subcutaneous injection, with doses titrated gradually upward over several weeks.[1] Exact amounts depend on body weight, age, and the condition under study. The dosage chart on this page summarises doses from published research. This is reference information only — not prescribing guidance.
How do you reconstitute Setmelanotide?
Unlike many research peptides that come as a lyophilised (freeze-dried) powder, setmelanotide in clinical research is supplied as a ready-to-use liquid solution in a multi-dose vial — no mixing or reconstitution is needed.[4] Vials should be stored refrigerated, protected from light, and inspected before each use. Always follow the specific study protocol or manufacturer instructions for handling.
Is Setmelanotide safe?
In phase 3 trials, the most common side effects were injection-site reactions, skin darkening (hyperpigmentation), nausea, and vomiting. No serious treatment-related adverse events were recorded in the POMC or LEPR trials.[1] Setmelanotide is a research compound; its safety profile outside controlled clinical studies is not fully established. This page does not provide medical advice.