Setmelanotide
Setmelanotide (Imcivree) is a daily injection approved only for obesity caused by a few rare genetic conditions or by brain injury near the hypothalamus. It is not a general weight-loss medicine.
Setmelanotide (known as Imcivree)
Also searched as: Imcivree.
Educational information. This page does not give dosing instructions or tell you what to take. Ask a prescriber about your own care.
In plain English
Setmelanotide (brand name Imcivree) works on a hunger-control pathway in the brain called the MC4R pathway. In some rare conditions that pathway is broken from birth or damaged by injury, which causes constant hunger and severe obesity. The drug is a daily injection that switches the pathway back on.
The FDA label covers three groups: people with obesity from POMC, PCSK1 or LEPR gene deficiency confirmed by genetic testing (age 2 and older), people with Bardet-Biedl syndrome (age 2 and older), and people with acquired hypothalamic obesity (age 4 and older, added in March 2026). It is not approved for ordinary obesity or for obesity linked to other genetic conditions.
The trials were small because the conditions are rare. In the POMC and LEPR studies, 8 of 10 and 5 of 11 people lost at least 10% of body weight in about a year, with no comparison group. In Bardet-Biedl syndrome, a randomized trial of 38 people found that 32.3% of those aged 12 and older with that syndrome reached at least a 10% loss after a year. Common effects include skin darkening and injection-site reactions.
Brand names and products
A generic name identifies the drug itself. A brand name identifies one company's product. One drug can come in several products with different forms and approved uses, so the brand name often tells you more about what a prescription is for.
Sold in the U.S. as Imcivree. A separate page for this brand has not been added to the atlas yet. The forms table below lists its approved use.
Approved and investigational. Setmelanotide is FDA-approved only for the conditions on its label. Any other use, including for common obesity, is outside the label.
How it works
Setmelanotide activates the melanocortin-4 receptor (MC4R) in the brain, a key part of the pathway that signals fullness. When genes upstream of MC4R are defective, or the hypothalamus is injured, the signal is weak. Directly activating MC4R is meant to restore it, which reduces hunger.
Forms and approval status
| Form | How it is taken | U.S. status |
|---|---|---|
| Setmelanotide injection (Imcivree) | Once daily. Used only for the specific conditions on the label. It is not a treatment for common obesity. | Approved in the U.S. (first in 2020) to reduce excess body weight and keep it off in people with obesity due to POMC, PCSK1 or LEPR deficiency confirmed by genetic testing (age 2 and older), Bardet-Biedl syndrome (age 2 and older), or acquired hypothalamic obesity (age 4 and older). It is not for common obesity. |
What the trials found
These are group averages from published trials in adults without diabetes unless stated. See how to read trial numbers before comparing.
Setmelanotide in POMC and LEPR deficiency
Share of people who lost at least 10% of their body weight at about 1 year. Every bar uses one scale, 0 to 100 percent.
- People studied
- 10 people with POMC deficiency obesity and 11 with LEPR deficiency obesity, age 6 and older, in two separate trials
- Length
- 52 weeks (about 1 year)
- Compared with
- None. These were open-label trials with no placebo group for the main result.
- What was measured
- Share of people who lost at least 10% of their body weight at about 1 year
- Analysis approach
- Everyone who received at least one dose and had a baseline measurement was counted.
- Other results
- Average change in the most-hunger score: down 27.1% in the POMC trial and down 43.7% in the LEPR trial (7 people in each analysis).
- Safety
- Injection site reactions occurred in everyone in both trials. Skin darkening was reported in all 10 people in the POMC trial. Nausea occurred in 5 of 10 (POMC) and 4 of 11 (LEPR). No serious treatment-related events were reported.
- Limits
- Very small trials, which is expected for such rare conditions. There was no comparison group for the main result. Funded by the manufacturer. These results apply only to the genetic conditions studied.
Sources: Clément K 2020, Imcivree (setmelanotide) injection: prescribing information
Safety
Based on the FDA-approved label for Imcivree. The official label is the controlling source for warnings. The points below are a summary and may be incomplete.
Boxed warning and label notes
- Setmelanotide injection (Imcivree): No boxed warning appears on the Imcivree label.
Warnings labels describe
- Can reduce sexual arousal or cause problems with sexual function.
- Depression and suicidal thoughts have been reported, so mood changes need attention.
- Serious allergic reactions can occur.
- Skin darkening, darkening of existing moles and new moles can occur, so skin checks are advised.
- In acquired hypothalamic obesity: risk of acute adrenal insufficiency, and of sodium imbalance in people who also have central diabetes insipidus.
Most common in trials
- Skin darkening (hyperpigmentation)
- Injection-site reactions
- Nausea
- Headache
- Diarrhea
- Abdominal pain
- Vomiting
- Depression
- Spontaneous penile erection
Less common but serious
- Serious allergic (hypersensitivity) reactions
- Depression and suicidal thoughts
- Acute adrenal insufficiency in acquired hypothalamic obesity
- Sodium imbalance in acquired hypothalamic obesity with central diabetes insipidus
What is still unknown
- Long-term effects over many years. The trials were small and the key POMC and LEPR studies had no comparison group.
- Results in Alström syndrome. The Bardet-Biedl trial called them inconclusive.
- The peer-reviewed TRANSCEND results. The company reported a 18.4% placebo-adjusted drop in BMI in 142 people with acquired hypothalamic obesity, but a full paper was not found for this atlas.
- Whether it would help common obesity. It is not approved for that and the label excludes it.
Compiled from public information: FDA-approved labels, manufacturer websites, ClinicalTrials.gov and published journal articles. Sources are listed at the bottom of this page.
Sources
- Imcivree (setmelanotide) injection: prescribing information Rhythm Pharmaceuticals, Inc., on DailyMed (U.S. National Library of Medicine). FDA-approved label, April 2026 listing. Official FDA label on DailyMed
- Rhythm Pharmaceuticals announces FDA approval of Imcivree for acquired hypothalamic obesity Rhythm Pharmaceuticals press release, March 19, 2026. Company announcement; not peer reviewed. Company announcement, not peer reviewed
- DailyMed: current FDA drug labels U.S. National Library of Medicine. Regulator
- Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials Clément K, et al. Lancet Diabetes Endocrinol. 2020;8(12):960-970. PMID 33137293. Funding: Rhythm Pharmaceuticals. Journal article
- Efficacy and safety of setmelanotide in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period Haqq AM, et al. Lancet Diabetes Endocrinol. 2022;10(12):859-868. PMID 36356613. Funding: Rhythm Pharmaceuticals. Journal article