Source: FDA label
| Molecular formula | C49H68N18O9S2 |
|---|---|
| Molecular weight | 1117.3 g/mol |
| Registered trials | 27 |
| PubChem CID | 11993702 |
| Drug class | Melanocortin 4 Receptor Agonist [EPC] |
| Brand names | Imcivree |
Mechanism of Action
12.1 Mechanism of Action Setmelanotide is an MC4 receptor agonist with 20-fold less activity at the melanocortin 3 (MC3) and melanocortin 1 (MC1) receptors. MC4 receptors in the brain are involved in regulation of hunger, satiety, and energy expenditure. Based on nonclinical evidence, setmelanotide may re establish MC4 receptor pathway activity to reduce food intake and promote weight loss through decreased caloric intake and increased energy expenditure in patients with obesity due to acquired
Key takeaways
- Setmelanotide is an MC4 receptor agonist sold under the brand name Imcivree.
- It is approved for acquired hypothalamic obesity and for certain genetically confirmed obesity syndromes.
- No boxed warning appears on the current label.
- 27 trials involving setmelanotide are registered, including completed phase 1 and phase 2 studies.
- Reported side effects center on nausea, vomiting, and skin pigment changes, based on FDA adverse event reports.
What setmelanotide is
Setmelanotide is a melanocortin 4 (MC4) receptor agonist. The MC4 receptor pathway in the brain helps regulate hunger, fullness, and how much energy the body burns. By activating this receptor, setmelanotide is thought to reduce food intake and increase energy expenditure, which together support weight loss. The drug has roughly 20-fold weaker activity at related melanocortin receptors, which is part of how it targets this pathway specifically.
What setmelanotide is approved for
Under the brand name Imcivree, setmelanotide is approved to reduce excess body weight and help maintain that reduction over the long term. It is indicated for patients aged 4 years and older with acquired hypothalamic obesity, and for patients aged 2 years and older with syndromic or monogenic obesity linked to Bardet-Biedl syndrome or to confirmed genetic variants in the POMC, PCSK1, or LEPR genes. Genetic testing confirming a pathogenic, likely pathogenic, or uncertain-significance variant is part of establishing eligibility for the genetic indications. The current label does not carry a boxed warning.
What the evidence shows
Setmelanotide has been studied across 27 registered clinical trials. The DAYBREAK study, a completed phase 2 trial, examined setmelanotide in participants with specific gene variants along the MC4R pathway. An earlier completed phase 1 trial looked at the drug's effects on energy expenditure in individuals with obesity. An expanded access protocol has also made setmelanotide available for patients with Bardet-Biedl syndrome outside of standard trial enrollment.
Reported side effects
Adverse event reports for setmelanotide most often involve gastrointestinal symptoms and skin changes: nausea (72 reports), vomiting (41), and diarrhoea (36), alongside skin hyperpigmentation (60) and related skin discolouration (35). Headache (39) and fatigue (35) also appear frequently, and a notable share of reports (68) were flagged as off-label use. These figures reflect the number of reports submitted to a federal adverse event database, not confirmed rates of occurrence or proof that the drug caused each event.
FAQ
What is setmelanotide used for?
Setmelanotide, sold as Imcivree, is approved to reduce excess body weight and help maintain that reduction in people with acquired hypothalamic obesity or with syndromic or monogenic obesity linked to Bardet-Biedl syndrome or confirmed POMC, PCSK1, or LEPR gene variants. It is approved for patients as young as 2 to 4 years old, depending on the specific condition.
How does setmelanotide work?
It is an MC4 receptor agonist, meaning it activates a brain pathway involved in hunger, fullness, and energy use. This activation is thought to lower food intake and raise energy expenditure, supporting weight reduction. It has much weaker activity at related melanocortin receptors, which helps target this specific pathway.
Does setmelanotide have a boxed warning?
No, the current FDA label for setmelanotide (Imcivree) does not include a boxed warning.
What side effects are most commonly reported with setmelanotide?
The most frequently reported issues are nausea, vomiting, and diarrhoea, along with skin hyperpigmentation and skin discolouration. Headache and fatigue are also commonly reported. These counts come from adverse event reports and reflect reporting frequency, not a confirmed rate or cause.
How much clinical research supports setmelanotide?
Setmelanotide has been evaluated in 27 registered clinical trials, including completed phase 1 and phase 2 studies. Trials such as DAYBREAK have focused on participants with specific gene variants along the MC4R pathway, and an expanded access program has supported use in Bardet-Biedl syndrome.
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Sources: FDA label (DailyMed) ClinicalTrials.gov FAERS adverse event data PubChem
Updated 2026-08-03