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Metabolic & weight

Setmelanotide

Also called Imcivree, BIM-22493

Setmelanotide is a small ring-shaped peptide that turns on the brain's MC4 'fullness' receptor. It is approved for rare types of severe obesity caused by certain gene problems, Bardet-Biedl syndrome, or damage to the hypothalamus. It is not meant for common obesity.

FDA-approvedApproved by the FDA for at least one use after large human trials.

All printable flashcards

Drawn from its published sequence: 8 residues, one bead each. Dashed arcs are ring bonds.

Overview

Setmelanotide is a small ring-shaped peptide that turns on the brain's MC4 'fullness' receptor. It is approved for rare types of severe obesity caused by certain gene problems, Bardet-Biedl syndrome, or damage to the hypothalamus. It is not meant for common obesity.

How it works

Established: setmelanotide activates MC4 receptors in the brain, which help control hunger, fullness and energy use. In the approved conditions this signal pathway is broken upstream, and the drug restores it. It is about 20-fold less active at MC3 and MC1 receptors; MC1 activity on skin pigment cells explains the skin darkening.

What research shows

  • TRANSCEND phase 3 RCT in acquired hypothalamic obesity (n=142): BMI fell 15.8% on setmelanotide vs a 2.6% rise on placebo at 52 weeks (placebo-adjusted -18.4%, p<0.0001) (Rhythm press release, SEC filing).
  • Label trials: skin hyperpigmentation in 58–83% and injection-site reactions in up to 96%, depending on population (FDA label).

Doses studied in people

Study or labelDose usedSource
FDA label, BBS or POMC/PCSK1/LEPR deficiency, age 12+2 mg subcutaneously once daily for 2 weeks, then 3 mg once daily (target)1
FDA label, acquired hypothalamic obesity, age 6+0.5 mg daily, stepped up every 2 weeks to a 3 mg daily target by week 71
FDA label, younger children (age 2–<6 BBS/genetic; 4–<6 HO)Start 0.5 mg daily; weight-based maintenance 0.5–2 mg daily1

Label doses shown; requires genetic or clinical confirmation of an approved condition.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Weekly protocol

How the schedule looks week by week. Each chart says where it comes from: a prescribing label, a clinical trial, or a protocol commonly reported online.

Imcivree label: BBS or POMC/PCSK1/LEPR deficiency, age 12+

Prescribing label

One week

D1D2D3D4D5D6D7

Once daily, at the beginning of the day · Subcutaneous injection

Dose by week

2 mgStarting · wk 1–2
3 mgMaintenance · wk 3+
Course
Ongoing
Note
If 2 mg is not tolerated, drop to 1 mg and return to 2 mg after at least 1 week; if 3 mg is not tolerated, stay at 2 mg.
Source
IMCIVREE (setmelanotide) prescribing information (FDA, revised 03/2026)

Imcivree label: acquired hypothalamic obesity, age 6+

Prescribing label

One week

D1D2D3D4D5D6D7

Once daily, at the beginning of the day · Subcutaneous injection

Dose by week

0.5 mgStarting · wk 1–2
1 mgwk 3–4
2 mgwk 5–6
3 mgMaintenance · wk 7+
Course
Ongoing
Note
Children aged 4 to under 6 use a separate weight-based schedule.
Source
IMCIVREE (setmelanotide) prescribing information (FDA, revised 03/2026)

Reference only, not a recommendation. Label and trial schedules were set for specific patients under medical supervision. Use the calculator only to understand the arithmetic.

Safety

  • Skin darkening and new or darker moles; full-body skin exams advised before and during treatment (label).
  • Spontaneous penile erections and sexual side effects; erections over 4 hours need emergency care (label).
  • Depression and suicidal thoughts — monitor (label).
  • In hypothalamic obesity: risk of acute adrenal insufficiency and sodium imbalance in patients with diabetes insipidus (label).
  • Common: nausea, vomiting, headache, diarrhea, injection-site reactions (label). Long-term safety beyond trial periods still being collected.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Storage and stability

Unopened vials refrigerated at 2–8°C; may be kept up to 25°C for 30 days; discard opened vials after 30 days (label).

General lab handling, not instructions for personal use. See Storage and stability.

History

Developed by Rhythm Pharmaceuticals; first FDA approval in 2020 for obesity due to POMC, PCSK1 or LEPR deficiency, later extended to Bardet-Biedl syndrome and to children as young as 2. In March 2026 the FDA approved it for acquired hypothalamic obesity (age 4+) based on the phase 3 TRANSCEND trial.

Common questions

Is setmelanotide FDA-approved?

Yes, as Imcivree, for obesity caused by certain rare genetic conditions (POMC, PCSK1 or LEPR deficiency) and Bardet-Biedl syndrome 1. In March 2026 it was also approved for acquired hypothalamic obesity in ages 4 and up 23.

What did the hypothalamic obesity trial show?

In the 142-person TRANSCEND trial, BMI fell 15.8% on setmelanotide vs a 2.6% rise on placebo after 52 weeks 2.

What doses are on the FDA label?

For ages 12 and up with the genetic conditions, the label lists 2 mg daily for 2 weeks, then 3 mg daily 1. Hypothalamic obesity and younger children start lower at 0.5 mg daily 1. These are label figures, not advice.

Does setmelanotide darken the skin?

Yes, often. Skin darkening affected 58% to 83% of trial participants, and the label advises full-body skin exams before and during treatment 1.

What other side effects are there?

The label lists injection-site reactions, nausea, vomiting, headache, unwanted erections and depression or suicidal thoughts 1. Erections lasting over 4 hours need emergency care 1.

How is setmelanotide stored?

Unopened vials are kept in the fridge at 2 to 8°C but can stay up to 25°C for 30 days, and opened vials are discarded after 30 days 1.

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Sources

  1. IMCIVREE (setmelanotide) prescribing information (2026) FDA label
  2. Rhythm Pharmaceuticals press release: FDA approval for acquired hypothalamic obesity (SEC Form 8-K exhibit, March 2026) Regulatory
  3. FDA approves expanded indication for Imcivree in hypothalamic obesity (PharmExec, March 2026) Journal
  4. WADA 2026 Prohibited List Regulatory

Last reviewed 2026-10-25 · How we research · Found an error? See our corrections policy.