Injectable peptide that reactivates the brain pathway that regulates hunger. Used in rare genetic obesities (POMC, PCSK1, or LEPR deficiency, Bardet-Biedl syndrome) and in acquired hypothalamic obesity.
Regulatory status
Approved (FDA / EMA)
Family
Melanocortin 4 receptor (MC4R) agonist
Scientific evidence
Moderate
Number of findings
2
Where it acts
Hormones and metabolism · Brain and sleep
Also known as
setmelanotide, Imcivree, RM-493
Regulatory status
FDA (US): Approved (2020, Imcivree) for obesity due to POMC, PCSK1, or LEPR deficiency; expanded in 2022 to Bardet-Biedl syndrome and in 2026 to acquired hypothalamic obesity (from age 4)
EMA (EU): Approved (2021, Imcivree) for obesity due to genetic deficiency of POMC (including PCSK1) or LEPR and Bardet-Biedl syndrome (from age 2); later also acquired hypothalamic obesity (from age 4)
Dose
Adults and those over 12 years: 2 mg subcutaneously daily for 2 weeks and then 3 mg daily if tolerated; in younger children the starting dose is lower and is adjusted by age and response (FDA/EMA label). Requires a confirmed genetic or clinical diagnosis.
Safety
Very common: darkening of the skin and moles (hyperpigmentation), injection-site reactions, nausea, and vomiting. Monitor for depression and suicidal thoughts. Skin checks are recommended. Only under prescription and the supervision of a specialized endocrinology team.
Differences between women and men
The label describes sexual effects: spontaneous erections in men and disturbances of sexual arousal in women. Not recommended in pregnancy (weight loss provides no benefit in pregnancy).
Effect by goal · level of evidence
Severe obesity due to POMC or LEPR deficiency
improvesModerateclinical trial (A)in people
≥10% weight loss in 80% (POMC)
Two open-label phase 3 trials without a placebo group (10 patients with POMC deficiency and 11 with LEPR deficiency). After one year, 80% of the POMC group and 45% of the LEPR group lost at least 10% of their weight. Hunger fell by about 27% and 44%.
Phase 3 trial with 38 patients and an initial placebo-controlled period. After 52 weeks, 32% of patients aged 12 years or older with Bardet-Biedl lost at least 10% of their weight. In Alström syndrome the result was inconclusive. Hyperpigmentation in 61%.
In these diseases, the signal that normally activates the MC4R receptor in the hypothalamus, the one that tells the brain there is enough energy, fails. Setmelanotide directly activates that receptor and, bypassing the broken link, reduces hunger and increases energy expenditure. It does not work for common obesity without these alterations.
What the evidence says
In people
Severe obesity due to POMC or LEPR deficiency. Two open-label phase 3 trials without a placebo group (10 patients with POMC deficiency and 11 with LEPR deficiency). After one year, 80% of the POMC group and 45% of the LEPR group lost at least 10% of their weight. Hunger fell by about 27% and 44%. PubMed 33137293
Obesity in Bardet-Biedl syndrome. Phase 3 trial with 38 patients and a placebo-controlled initial period. After 52 weeks, 32% of patients aged 12 years or older with Bardet-Biedl lost at least 10% of their weight. In Alström syndrome the result was inconclusive. Hyperpigmentation occurred in 61%. PubMed 36356613