Imcivree (setmelanotide) is a once-daily injection that acts directly on the brain's hunger-control pathway. In March 2026 it became the first FDA-approved treatment for acquired hypothalamic obesity, the severe weight gain and hunger that can follow a brain tumor such as a craniopharyngioma, or its surgery or radiation. It is approved for adults and children age 4 and older.
The hypothalamus is a small area at the base of the brain, just above the pituitary gland. It acts as the body's “weight thermostat,” balancing hunger, fullness, and how much energy the body burns. When it is damaged, that system breaks down: people may feel constantly hungry, never feel full, and gain weight quickly even while eating carefully. Standard diet, exercise, and many weight-loss medicines often work poorly because the problem is in the brain's signaling, not willpower. Learn more about weight and metabolism in our obesity & metabolism guide.
Who Is Imcivree For?
| Condition | Who | Approved |
|---|---|---|
| Acquired hypothalamic obesity (after a tumor such as craniopharyngioma, its treatment, or other hypothalamic injury) | Adults and children age 4+ | March 2026 |
| Bardet-Biedl syndrome (BBS) | Age 2+ | 2022 |
| Genetic POMC, PCSK1, or LEPR deficiency (confirmed by genetic testing) | Age 2+ | 2020 |
Imcivree is not a general weight-loss medicine. It is meant for these specific causes of obesity, where the brain's MC4R pathway is disrupted.
How Does It Work?
Setmelanotide activates the melanocortin-4 receptor (MC4R), a switch in the hypothalamus that normally signals fullness and increases energy use. When injury or a gene change disrupts the signals that feed into this switch, setmelanotide can turn it on directly, helping restore a sense of fullness and reduce constant hunger.
Results
In the 52-week TRANSCEND trial of 142 people with acquired hypothalamic obesity, those taking Imcivree lowered their BMI by about 16% on average, while BMI rose about 2% on placebo, a difference of nearly 19%. People age 12 and older also reported meaningfully less hunger.
How It's Taken
- A small injection under the skin (belly, thigh, or arm) once a day, at the start of the day, with or without food
- Drawn from a vial with a 1-mL syringe; let the vial warm to room temperature for about 15 minutes first
- For hypothalamic obesity, it starts at 0.5 mg daily for 2 weeks and is increased gradually as tolerated, usually to 3 mg daily for people age 6 and older (children age 4–5 are dosed by weight)
- Missed a dose? Skip it and take the next dose at the usual time
Side Effects
- Skin darkening, including darker freckles or moles and new moles — a full skin check is recommended before starting and periodically after
- Injection-site redness, itching, or bruising
- Nausea, vomiting, diarrhea, stomach pain, headache — usually early on
- Spontaneous erections in males and sexual side effects in females. An erection lasting more than 4 hours needs emergency care
⚠️ Important safety information: Imcivree can cause or worsen depression and suicidal thoughts — families should watch for mood changes and call right away. People with hypothalamic obesity often also have pituitary hormone deficiencies, so we monitor for adrenal insufficiency (weakness, vomiting, dizziness) and, in those with diabetes insipidus, for sodium changes. It should be stopped if pregnancy occurs, and it is not recommended while breastfeeding or with severe kidney disease.
Is Imcivree Right for You or Your Child?
If you or your child gained a lot of weight, or developed constant hunger, after a craniopharyngioma or other tumor near the pituitary, or after brain surgery or radiation, it is worth asking about hypothalamic obesity. Our endocrinologists can review the history, manage any pituitary hormone deficiencies that often come with it, and discuss whether Imcivree is an option. Genetic testing may be recommended for severe obesity that began in early childhood.
Key Takeaways
- Imcivree (setmelanotide) is the first FDA-approved treatment for acquired hypothalamic obesity (March 2026, age 4+)
- Hypothalamic obesity is weight gain and constant hunger after damage to the brain's weight-control center, often after a craniopharyngioma
- Also approved for Bardet-Biedl syndrome and genetic POMC, PCSK1, or LEPR deficiency (age 2+)
- Once-daily injection; lowered BMI by about 16% in one year versus a 2% rise on placebo
- Common side effects include skin and mole darkening, nausea, and injection-site reactions
- Mood, adrenal function, and sodium need monitoring
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