Library / Weight and metabolic

Setmelanotide

Also known as Imcivree

Approved medicine

Melanocortin 4 receptor agonist peptide. Approved only for obesity caused by certain rare genetic disorders of the melanocortin pathway.

Not approved in Australia. Setmelanotide is not on the Australian Register of Therapeutic Goods. Only a prescriber can decide whether a medicine suits you and at what dose. This page is information, not a recommendation.

Background

Synthetic cyclic peptide that activates the melanocortin 4 receptor, originally discovered at Ipsen and developed by Rhythm Pharmaceuticals. FDA approved it as Imcivree in 2020 for rare genetic forms of obesity.

How it is thought to work

Replaces a missing signal in the brain's leptin and melanocortin pathway, which controls hunger. When genetic faults break this pathway, activating MC4R directly can reduce hunger and body weight.

What is claimed, and the evidence

Claim	Evidence	Notes
Weight reduction in obesity due to POMC, PCSK1 or LEPR deficiency confirmed by genetic testing	Approved use	Imcivree label. In phase 3 trials, 80% of POMC and 45% of LEPR participants lost at least 10% of weight at about 1 year.
Weight reduction in Bardet-Biedl syndrome	Approved use	Imcivree label. About 32% of patients aged 12 and over lost at least 10% of body weight at 52 weeks.
Weight reduction in acquired hypothalamic obesity (from age 4)	Approved use	Added to the current US label.
Weight loss in common obesity	No published evidence	The label states it is not expected to work in general (polygenic) obesity.

Side effects

Effect	How often	Notes
Skin darkening (hyperpigmentation) and darkening or new moles	Common	61% to 67% in trials; the label advises full skin exams before and during treatment.
Injection site reactions	Common	Reported in nearly all participants in the POMC and LEPR trials.
Nausea, vomiting, diarrhoea and abdominal pain	Common	Listed as most common on the label.
Headache	Common	Label.
Spontaneous erections and sexual adverse reactions	Common	Label warning; seek urgent care for an erection lasting over 4 hours.
Depression and suicidal thoughts Serious	Common	Label warning; depression is among the most common reactions in at least one indication.
Serious allergic reactions including anaphylaxis Serious	Rare	Label warning.
Acute adrenal insufficiency and sodium imbalance in hypothalamic obesity Serious	Uncommon	Label warnings for this group.

Warnings

Only works for specific rare genetic or hypothalamic causes of obesity; not expected to work in common obesity.
Monitor for depression and suicidal thoughts.
Causes skin darkening and can darken or create moles, so skin checks are advised.
Not found on the Australian Register of Therapeutic Goods (September 2026).

Regulatory status

Australia: Not found on the ARTG (search September 2026).
United States: FDA approved (Imcivree, 2020) for obesity due to specific rare genetic conditions (POMC, PCSK1 or LEPR deficiency, Bardet Biedl syndrome).

Sources

Also in Weight and metabolic

From the VialOwl library, reviewed 26 September 2026. For education and general information. It is not medical advice and not a recommendation to use Setmelanotide.