# Setmelanotide

A daily injection for obesity caused by a rare gene fault or by damage to the brain's hunger centre. It is not expected to work for ordinary obesity and is not approved for it.

Also called: Imcivree
Source page: https://peplogue.com/peptides/setmelanotide/
Updated: 2026-10-22. Not medical advice.

## How it works

- Where it acts: MC4 receptors in the hypothalamus, the brain area that sets hunger.
- What it changes: It restores the fullness signal when the pathway is broken by certain gene faults (POMC, PCSK1, LEPR or Bardet-Biedl syndrome) or by damage to the hypothalamus.
- What people notice: In those rare conditions, hunger falls within weeks. Skin darkening and injection-site reactions are common.

## What the evidence shows

- **Obesity from rare genetic causes**: Proven. For POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome. At least 10% weight loss in 8 of 10 people with POMC or PCSK1 deficiency and 5 of 11 with LEPR deficiency.
- **Obesity after damage to the hypothalamus**: Proven. Approved in the US in March 2026, from age 4. The EU, UK, Japan and Canada followed between May and September 2026.

## Side effects and risks

- serious: Depression and suicidal thoughts have been reported. The label asks for monitoring.
- common: Skin and moles darken in most people who take it.
- common: Spontaneous erections and other sexual side effects.
- common: Nausea and injection-site reactions.

Who should avoid it: Anyone without one of the named conditions.

## How it is taken

Daily injection under the skin. Adults and teenagers usually start at 2 mg and move to 3 mg. For hypothalamic obesity the starting dose is 0.5 mg. Specialist prescribing only.

## Legal status

- United States: undefined. Imcivree, for the named rare conditions only.
- European Union: undefined. Imcivree, for the same rare conditions. Hypothalamic obesity was added in spring 2026; launches are expected in 2027.
- Spain: undefined. Imcivree is authorised and marketed in Spain (CIMA), prescription only. SNS funding was not verified.
- Germany: undefined. Imcivree on sale since Jun 2022 for rare genetic obesity; G-BA took it off the lifestyle list, so GKV can pay. Cover for the 2026 label addition not checked.
- France: undefined. Imcivree sold since 2022: 65%, liste I, hospital prescription, endocrinologist renewal. Early access for hypothalamic obesity active (renewed Jan 2026).
- Italy: undefined. Imcivree: classe H, limited prescription via regional centres, reimbursed for Bardet-Biedl syndrome (Determina 57/2024). Other uses not verified.
- Netherlands: undefined. Imcivree is listed for POMC/LEPR deficiency, Bardet-Biedl and hypothalamic obesity. Insured under conditions (Bijlage 2). Dutch supply not confirmed.
- United Kingdom: undefined. Imcivree, specialist use. Obesity after hypothalamic injury was added in August 2026.
- Canada: undefined. Imcivree. Obesity after hypothalamic injury was added in September 2026.
- Australia: undefined

## Questions people ask

**Does setmelanotide work for ordinary obesity?**

No. It is not expected to work for ordinary obesity and is not approved for it. It restores a broken hunger pathway in a few rare conditions.

**Who is setmelanotide approved for?**

People with obesity caused by POMC, PCSK1 or LEPR deficiency or Bardet-Biedl syndrome, and obesity after damage to the hypothalamus. The hypothalamic use was approved in the US in March 2026 from age 4, and the EU, UK, Japan and Canada followed between May and September 2026.

**How much weight do people lose on setmelanotide?**

In trials, at least 10% weight loss was seen in 8 of 10 people with POMC or PCSK1 deficiency and 5 of 11 with LEPR deficiency.

**Does Imcivree darken your skin?**

Yes. Skin and moles darken in most people who take it. Spontaneous erections, nausea and injection-site reactions are also common.

**What are the serious risks of setmelanotide?**

Depression and suicidal thoughts have been reported, and the label asks for monitoring.

## Sources

- Imcivree US prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9
- EMA: Imcivree product page: https://www.ema.europa.eu/en/medicines/human/EPAR/imcivree
- Rhythm: FDA approval for hypothalamic obesity (19 Mar 2026): https://www.sec.gov/Archives/edgar/data/1649904/000162828026019995/ex991hopdufapressrelease.htm
- Rhythm: news releases (UK, Japan and Canada approvals): https://ir.rhythmtx.com/news-releases