Approved drugMC4 receptor agonist (melanocortin)

Setmelanotide

Imcivree, RM-493

Common dose: 0.5 → 3 mg once daily
Cycle: Continuous
Form: Ready-made product

An eight-amino-acid ring-shaped peptide that switches on the MC4 receptor, a brain switch for hunger and energy use, in people whose own signal to it is broken. It cuts hunger and weight in those conditions; skin darkening is its most common side effect.

Evidence. FDA-approved as Imcivree for obesity caused by rare defects in the brain’s MC4 receptor pathway: POMC, PCSK1 or LEPR deficiency (2020), Bardet-Biedl syndrome (2022) and acquired hypothalamic obesity after brain tumors or injury (March 2026); also approved in the EU, UK and Canada, and in Japan for hypothalamic obesity. In TRANSCEND (142 people with hypothalamic obesity), BMI fell 15.8% vs a 2.6% rise on placebo over 52 weeks. It isn’t approved, or expected to work, for common obesity.

What it’s used for

Approved uses first, then uses tested in people, then claims that rest on animal studies or user reports.

Acquired hypothalamic obesity: LabelApproved from age 4 for obesity after brain tumors, surgery or injury affecting the hypothalamus. In TRANSCEND, BMI fell 15.8% vs a 2.6% rise on placebo over 52 weeks.
Obesity in Bardet-Biedl syndrome: LabelApproved from age 2 for this rare genetic syndrome. BMI fell 4.6% vs 0.1% on placebo over 14 weeks, and 7.9% on average after a year of treatment.
Obesity from POMC, PCSK1 or LEPR deficiency: LabelApproved from age 2 when gene testing confirms it. After a year, 80% with POMC or PCSK1 and 46% with LEPR deficiency lost at least 10% of body weight.
Obesity with single-copy gene variants: TrialNegative per the developer: in EMANATE (295 people with one altered copy of POMC, PCSK1, LEPR, SRC1 or SH2B1), BMI didn’t fall significantly more than on placebo at 52 weeks.
Common obesity: TrialNot shown: in a 74-person, 90-day trial, weight fell 2.0% vs 0.3% on placebo, not a significant difference. The label says it isn’t expected to work in general obesity.
Alström syndrome: TrialInconclusive: in the Bardet-Biedl trial, the few people with Alström syndrome, another rare genetic obesity, showed no clear benefit; it isn’t approved for it.
Prader-Willi syndrome: No studyUnproven: an 18-person phase 2 trial in this genetic cause of constant hunger is under way, with no results yet.
Tanning: No studyNot a use: skin darkening, from its action on pigment-cell (MC1) receptors, is a side effect in most users, and no study has tested it for tanning.

Label: an approved use. Trial: tested in people, with the result. No study: nothing published supports it.

Every compound’s uses, by body system: evidence map, and by condition: conditions A to Z.

Status

Approval: Approved in the US as Imcivree: November 2020 for obesity from POMC, PCSK1 or LEPR deficiency confirmed by genetic testing, June 2022 for Bardet-Biedl syndrome (both now from age 2), and March 19, 2026 for acquired hypothalamic obesity from age 4. Also approved in the EU (2021), the UK and Canada, and in Japan for hypothalamic obesity (August 2026).
Approval history: 2020US FDA: Imcivree: obesity from POMC, PCSK1 or LEPR deficiency
2021EU (EMA): Imcivree: obesity from POMC, PCSK1 or LEPR deficiency
2022US FDA: Imcivree: obesity in Bardet-Biedl syndrome
2026US FDA: Imcivree: acquired hypothalamic obesity, from age 4
2026EU (EMA): Imcivree: acquired hypothalamic obesity added
2026Japan (PMDA): Imcivree: acquired hypothalamic obesity
European Union: Authorized since July 2021 as Imcivree: obesity from POMC, PCSK1 or LEPR deficiency and Bardet-Biedl syndrome (from age 2), and acquired hypothalamic obesity (from age 4) since April 2026.
United Kingdom: Licensed by the MHRA (PLGB 55587/0001) for the same three uses and age limits, per the UK summary of product characteristics revised August 2026.
Canada: Approved May 2023 and marketed since July 2023 for Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiency (from age 6); hypothalamic obesity (from age 4) added September 2026.
Australia: No product registered; the TGA lists no product information for setmelanotide (October 2026).
Sport (WADA 2026): Not banned in sportNot named on the 2026 list; it isn’t a corticotrophin (S2.2.2) or another listed peptide hormone, and S0 doesn’t apply to an approved drug.

Sport status follows the WADA Prohibited List in force since January 1, 2026; athletes should confirm with their anti-doping organization. Checked October 5, 2026. Status outside the US checked October 7, 2026 against EMA, MHRA, Health Canada and TGA records. By country: EU, UK, Canada, Australia. Status of every compound.

How it works

LabelBased on the product label.

Not known

The label calls the pathway effect nonclinical (animal and lab evidence). Why responses vary between conditions, its long-term effects in young children, and any melanoma risk from its pigment effect are unknown.

Protocol

Label

Imcivree

Acquired hypothalamic obesity, adults: 0.5 mg once daily for 2 weeks, then 1 mg (weeks 3–4), 2 mg (weeks 5–6) and 3 mg from week 7, each step only if tolerated.

Label

Imcivree

Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency, adults: 2 mg once daily for 2 weeks, then 3 mg. If 2 mg isn’t tolerated, 1 mg for at least a week first; if 3 mg isn’t tolerated, back to 2 mg.

Frequency: Once daily
Route: Subcutaneous injection (belly, thigh or arm)
Timing: At the beginning of the day, with or without food.
Cycle: Continuous. The label treats it as long-term therapy; weight and hunger return within weeks of stopping.
Continuous, shown over 26 weeks

Common protocols

The ways Setmelanotide is most often run, each tagged with where it comes from.

Acquired hypothalamic obesity

Label

Dose: 0.5 mg rising to 3 mg
How often: Once daily
How long: Long-term

Adults: 2 weeks each at 0.5, 1 and 2 mg, then 3 mg, each step only if tolerated. Not recommended with severe kidney impairment.

Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency

Label

Dose: 2 mg rising to 3 mg
How often: Once daily
How long: Long-term

Adults: 2 mg for 2 weeks, then 3 mg. If 2 mg isn’t tolerated, 1 mg for at least a week first; if 3 mg isn’t tolerated, 2 mg.

Severe kidney impairment

Label

Dose: 0.5 mg rising to 1.5 mg
How often: Once daily
How long: Long-term

Adults with Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency and eGFR 15–29: 0.5 mg for 2 weeks, then 1 mg, then 1.5 mg. Not recommended in kidney failure.

EU and UK labels

Label

Dose: 0.5–3 mg (hypothalamic obesity); 1–3 mg (POMC or LEPR deficiency)
How often: Once daily
How long: Long-term

Adults with hypothalamic obesity step up weekly: 0.5, 1, 2, then 3 mg if needed. Adults with POMC or LEPR deficiency start at 1 mg for 2 weeks, then 2 mg, up to 3 mg.

Imcivree step-up, acquired hypothalamic obesity (adults)

Period	Dose
Weeks 1–2	0.5 mg
Weeks 3–4	1 mg
Weeks 5–6	2 mg
Week 7 on (maintenance)	3 mg

Each step only if the previous dose is tolerated; if 0.5 mg isn’t tolerated, the label says to stop. For Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiency, adults start at 2 mg for 2 weeks, then 3 mg.

Taking it

Where it goes

Under the skin of the belly, thigh or arm, a different site each day, using a 1 mL syringe with a 28- or 29-gauge needle; never into a vein or muscle (label). The vial is warmed to room temperature first.

If you miss a dose

Imcivree label: skip it and resume the once-daily schedule with the next dose; don’t double up.

Missed doses for every compound

What to expect

First 2–3 weeks
Skin darkening usually starts within 2–3 weeks, lasts while treatment continues and fades after stopping, per the UK label.
Label
First month
Nausea and vomiting are most common early and are usually mild, per the UK label.
Label
Week 52 (hypothalamic obesity)
BMI fell 15.8% vs a 2.6% rise on placebo; 61% vs 5% cut BMI by at least 10%.
Label
1 year (POMC, PCSK1 or LEPR deficiency)
80% with POMC or PCSK1 deficiency and 46% with LEPR deficiency lost at least 10% of body weight; average losses were 23% and 10%.
Label
After stopping
During a 4-week switch to placebo, people regained about 5 kg and hunger rose; both improved again on restarting.
Label

Side effects and what to do

Skin darkening (label: 58% vs 10% on placebo in hypothalamic obesity; 63–78% in other trials), with new or darker moles (15% vs 6%)

Caused by its action on pigment cells and reverses after stopping. The label calls for full-body skin checks before and during treatment.

Nausea 55% and vomiting 38% (label, hypothalamic obesity; placebo 25% and 19%)

Most common early. If the starting dose isn’t tolerated, the label lowers it or stops the drug.

Injection-site reactions (label: 51% in Bardet-Biedl syndrome, 96% in POMC, PCSK1 or LEPR deficiency)

Redness, itching, swelling or bruising. Rotate sites daily.

Spontaneous erections (label: 7% vs 4% in hypothalamic obesity; about a quarter of males in other trials)

An erection lasting over 4 hours needs emergency care.

Depression (label: 26%, and suicidal thoughts 11%, in the POMC, PCSK1 and LEPR trials, which had no placebo group)

The label says to watch mood and consider stopping if suicidal thoughts or lasting depression appear.

Stop and get medical help

Signs of a serious allergic reaction (face or throat swelling, trouble breathing, widespread hives), an erection lasting over 4 hours, suicidal thoughts or worsening depression, or, in hypothalamic obesity, signs of adrenal crisis such as severe weakness, vomiting or fainting.

Can it cause …?

The side effects people ask about most, answered one by one. Each answer says where it comes from.

Tiredness: LabelFatigue: 30% in the year-long POMC, PCSK1 and LEPR trials and 5% in Bardet-Biedl syndrome; weakness 19%. These trials had no placebo group.
Headache: LabelHeadache: 37% vs 31% on placebo in hypothalamic obesity, and 41% in the POMC, PCSK1 and LEPR trials.
Nausea or vomiting: LabelNausea 55% vs 25% and vomiting 38% vs 19% on placebo in hypothalamic obesity, mostly in the first month and usually mild, per the UK label.
Diarrhea or constipation: LabelConstipation 12% vs 6% on placebo in hypothalamic obesity. Diarrhea 37% and belly pain 33% in the POMC, PCSK1 and LEPR trials, which had no placebo group.
Dizziness: LabelDizziness: 12% vs 4% on placebo in hypothalamic obesity; 15% in the POMC, PCSK1 and LEPR trials, plus vertigo 15%.
Trouble sleeping: LabelTrouble sleeping: 15% in the year-long POMC, PCSK1 and LEPR trials (no placebo group). The UK label also lists sleep disorder and nightmares as uncommon.
Hair loss: LabelHair loss: 11% in the POMC, PCSK1 and LEPR trials (no placebo group). Hair color changes also occur, part of its pigment effect.
Acne, rash or skin changes: LabelSkin darkening in most users: 58% vs 10% on placebo in hypothalamic obesity and 63–78% in other trials. New or darker moles 15% vs 6%; injection-site reactions are common.
Water retention or swelling: LabelFluid retention isn’t a listed side effect. Injection-site swelling is common, and face or throat swelling can signal a serious allergic reaction, which the label lists.
Joint or muscle pain: LabelJoint pain 19% and back pain 33% in the year-long POMC, PCSK1 and LEPR trials, which had no placebo group.
Anxiety, low mood or irritability: LabelLabel warning: depression 26% and suicidal thoughts 11% in the POMC, PCSK1 and LEPR trials (no placebo group); aggression 5% in Bardet-Biedl syndrome.
Low or high blood sugar: LabelNot a listed side effect; blood sugar measures improved slightly with weight loss. In hypothalamic obesity, low blood sugar can be a sign of adrenal insufficiency, per the UK label.
Fast heartbeat or blood pressure changes: LabelThe US label lists no heart effects; QT wasn’t prolonged at 2.3 times the top dose. The UK label wants heart rate and blood pressure checked at least twice yearly.
More hunger: LabelIt reduces hunger: in hypothalamic obesity, maximum daily hunger fell 2.27 points vs 1.44 on placebo (0–10 scale). Hunger and weight return within weeks of stopping.
Liver strain: LabelThe UK label lists raised liver enzymes (ALT) as common and other liver test rises as uncommon; no serious liver injury is described. Not studied in liver impairment.
Kidney problems: LabelNot a listed side effect, but the kidneys help clear it: severe impairment nearly doubles exposure, so doses are cut or it isn’t used.
Cancer risk: LabelNo tumors in a 26-week study in cancer-prone mice. It darkens moles and causes new ones, so the label requires regular skin exams; melanoma risk isn’t addressed.

Label: from the prescribing information. A side effect that hasn’t been reported can still happen, especially with long or high-dose use. Any of these across every compound: the side-effect finder.

Who should avoid it

What its label rules out or warns about, most important first.

Serious allergy to setmelanotide: LabelRuled out after a prior serious reaction, including anaphylaxis, to setmelanotide or any ingredient.
History of depression or suicidal thoughts: LabelThese may recur on treatment. The label says to watch mood and consider stopping with suicidal thoughts or lasting depression.
Many moles or past melanoma: LabelNot ruled out, but it darkens existing moles and causes new ones; the label requires full-body skin exams before and during treatment. It doesn’t address melanoma history.
Hypothalamic obesity with adrenal insufficiency: LabelSerious adrenal crises occurred in 5% vs 0% on placebo. The US label says to watch for them; the UK label says to replace cortisol before starting.
Hypothalamic obesity with diabetes insipidus: LabelBlood sodium fell too low in 6% vs 2% on placebo and rose too high in 5% vs 4%; the label advises checking sodium as fluid intake changes.
Severe kidney disease: LabelNot recommended in kidney failure, or for hypothalamic obesity with severe impairment; lower doses are used for the genetic conditions.
Pregnancy or breastfeeding: LabelThe label says to stop when pregnancy is recognized unless benefits outweigh risks, since weight loss may harm a fetus, and advises against breastfeeding; it enters rat milk.

Interactions

Only interactions stated on a product label or measured in a human study are listed.

Treatments for diabetes insipidus or adrenal insufficiency (such as desmopressin or hydrocortisone) in hypothalamic obesity: LabelThe US label says to adjust diabetes insipidus treatment as needed; the UK label adds monitoring and adjusting any drug affected by changes in weight, cortisol or nutrition.

Label: a product label rules it out, warns about it or lists the interaction. This isn’t a complete list: a pharmacist or doctor can check a specific medicine or condition. Every documented interaction, by medicine: drug interactions.

Special situations

What the label and studies say about pregnancy, breastfeeding, kidney and liver problems, age and surgery.

Pregnancy: LabelNo human data. The label says to stop once pregnancy is recognized unless benefits outweigh risks, since weight loss may harm a fetus. Rat and rabbit studies showed no birth defects.
Breastfeeding: LabelNot recommended while breastfeeding. It passes into rat milk, and there are no human data; the vial’s benzyl alcohol preservative is unlikely to reach the baby.
Kidney problems: LabelSevere impairment nearly doubles exposure: lower doses for the genetic conditions, not recommended for hypothalamic obesity, and not recommended in kidney failure. No change for mild or moderate impairment.
Liver problems: LabelNot studied in liver impairment. The US label gives no dose advice; the UK label urges caution because the benzyl alcohol preservative could build up.
Older adults: LabelThe label says its trials included no one 65 or older (one trial enrolled people up to 66), so whether older adults respond differently is unknown.
Children and teens: LabelApproved from age 2 for Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiency, and from age 4 for hypothalamic obesity; not established at younger ages.
Surgery and anesthesia: PrecautionNo data; tell the surgical team about it. In hypothalamic obesity, adrenal insufficiency and diabetes insipidus, both label concerns, need planning around surgery.

Label: what the prescribing information says. Precaution: not studied, so the caution follows from how it works or from a related drug. Ages are given as approved or studied; this site never gives doses for children. Across every compound: pregnancy, breastfeeding, kidney disease, liver disease, older adults and surgery.

Tracking and pairing

Worth tracking

Full-body skin exam before starting and periodically
Mood, depression or suicidal thoughts
Adrenal function and signs of adrenal crisis (hypothalamic obesity)
Blood sodium if diabetes insipidus is present
Heart rate and blood pressure (UK label: at least every 6 months)
Kidney function, which sets the dose

Often paired with

Usually run on its own.

Human studies

5 key published human studies, with how many people took part. Animal studies aren’t listed here.

2026120 people

BMI fell 16.5% vs a 3.3% rise on placebo in people aged 4 to 66, and hunger scores fell more; serious adverse events 28% vs 8%.

Design
Randomized double-blind placebo-controlled trial (phase 3) in acquired hypothalamic obesity
Dose
Up to 3 mg once daily (adult maximum) after dose escalation
Length
52 weeks after escalation

Miller et al., N Engl J Med 2026 (TRANSCEND), PMID 42418774
202021 people

8 of 10 with POMC deficiency and 5 of 11 with LEPR deficiency lost at least 10% of body weight; most-hunger scores fell 27% and 44%.

Design
Two single-arm open-label trials (phase 3) with an 8-week placebo-controlled withdrawal, in POMC or LEPR deficiency
Dose
Up to 3 mg once daily (adult maximum)
Length
About 1 year

Clément et al., Lancet Diabetes Endocrinol 2020, PMID 33137293
202238 people

32.3% of those 12 and older with Bardet-Biedl syndrome lost at least 10% of body weight after 52 weeks; results in Alström syndrome were inconclusive.

Design
Randomized double-blind placebo-controlled trial (phase 3) with a 52-week open-label period, in Bardet-Biedl and Alström syndromes
Dose
Up to 3 mg once daily (adult maximum)
Length
14 weeks placebo-controlled, then 52 weeks open-label

Haqq et al., Lancet Diabetes Endocrinol 2022, PMID 36356613
202418 people

BMI fell 15% on average and 16 of 18 cut BMI by at least 5%; 12 people in the extension had a 26% BMI drop at 12 months.

Design
Open-label single-arm trial (phase 2) in hypothalamic obesity
Dose
Titrated to 3 mg once daily (adult maximum)
Length
16 weeks, plus extension

Roth et al., Lancet Diabetes Endocrinol 2024, PMID 38697184
201512 people

Resting energy use rose 6.4% (about 111 kcal a day) vs placebo, with a shift toward burning fat and no change in heart rate or blood pressure.

Design
Randomized double-blind placebo-controlled crossover trial in adults with common obesity
Dose
1 mg per 24 hours by continuous infusion under the skin
Length
72 hours per treatment

Chen et al., J Clin Endocrinol Metab 2015, PMID 25675384

All human studies on Vial Guide

Trials under way

Registered trials that are still running, or that finished without published results, most important first. Checked on ClinicalTrials.gov, October 7, 2026.

Phase 3NCT06760546
Setmelanotide vs placebo in about 39 people aged 4 and older with congenital (present from birth) hypothalamic obesity, a sub-study of TRANSCEND: change in BMI
Recruiting since September 2025; main results expected March 2027
Phase 2NCT06772597
Open-label setmelanotide for up to 52 weeks in 18 people aged 6–65 with Prader-Willi syndrome, a genetic cause of constant hunger: safety, weight and hunger
Active, not recruiting; primary completion expected October 2026
Phase 3NCT05093634
EMANATE: setmelanotide vs placebo for 52 weeks in 296 people with single-copy variants in POMC, PCSK1, LEPR, SRC1 or SH2B1
Completed June 2026; the developer reported in March 2026 that all four groups missed their main goal; not published
Phase 3NCT06596135
Open-label extension for 28 people continuing setmelanotide after earlier trials: long-term safety
Completed June 2026; no results posted
Phase 4NCT07674290
Single-center study of real-world setmelanotide use in about 200 people with Bardet-Biedl syndrome and other MC4R pathway disorders: BMI, blood fats and liver fat
Recruiting; completion expected December 2030

Every compound’s registered trials: trials under way.

Limits of the evidence

Evidence comes from small trials: 21 people with POMC, PCSK1 or LEPR deficiency treated openly for a year, 44 with Bardet-Biedl syndrome (14 weeks placebo-controlled) and 12 young children. Only TRANSCEND (142 people with hypothalamic obesity) compared it with placebo for a full year. Hardly anyone over 65 was studied, no trial measured heart outcomes, no drug-interaction studies exist, and weight returned within weeks of stopping. In carriers of single gene variants, its developer reported no significant benefit.

How it’s supplied

A ready-made solution, 10 mg/mL, in a 1 mL multiple-dose vial (10 mg per vial). Drawn up with a 1 mL syringe and injected under the skin once daily by the patient or a trained caregiver. It’s used as supplied, so the calculator and dose log don’t apply.

Nothing is mixed: the 10 mg/mL solution is drawn straight from the vial, so 0.1 mL is 1 mg and the 3 mg dose is 0.3 mL. Each vial is discarded 30 days after first use.

Datasheet

Half-life: about 11 hours LabelEffective half-life with daily 3 mg injections under the skin in adults; levels peak about 8 hours after a dose and reach steady state within 2 days. About 39% leaves unchanged in urine.
Type: Peptide, 8 amino acids
Molecular weight: 1,117.3 g/mol
Formula: C₄₉H₆₈N₁₈O₉S₂
Sequence: (Ac)-RC-(D-Ala)-H-(D-Phe)-RWC-NH2A disulfide bond between the two cysteines closes the ring
Storage before use: Not a powder: a ready-made solution in a multiple-dose vial. Unopened: refrigerate at 2–8 °C in the carton until the expiry date, or keep at 2–25 °C for up to 30 days.
After mixing or opening: After the first puncture, keep in the carton in the fridge or at up to 25 °C (brief excursions to 30 °C) and discard after 30 days.

Half-life: Imcivree prescribing information (rev. 03/2026), section 12.3
Molecule: Imcivree label rev. 03/2026, section 11 (anhydrous free base; supplied as the acetate, 2–4 acetates per molecule); PubChem CID 11993702; UNII N7T15V1FUY
Storage: Label Imcivree prescribing information (rev. 03/2026), section 16, and Instructions for Use

Every compound side by side: the half-life chart and the storage chart.

Identifiers

UNII (FDA): N7T15V1FUY; 224I1W20I7 (acetate)
PubChem CID: 11993702; 155491122 (acetate)
DrugBank: DB11700
ATC code: A08AA12
CAS number: 920014-72-8 (setmelanotide); 1504602-49-6 (acetate)
Development codes: RM-493 (Rhythm Pharmaceuticals), BIM-22493
Brand names: Imcivree (US, EU, UK, Canada, Japan)
First described: First described in 2013 as BIM-22493 (RM-493) in obese rhesus monkeys. First approved: US, November 2020.

Every compound’s numbers: the identifiers table.

Product form and quality

Imcivree is a ready-made solution of setmelanotide acetate, 10 mg/mL; doses refer to setmelanotide itself. It contains benzyl alcohol and phenol as preservatives, which is why the UK label warns about use under age 3.

Cautions

Skin darkening in most users (58% vs 10% on placebo in hypothalamic obesity, up to 78% in other trials), plus darker or new moles; the label calls for full-body skin exams before and during treatment.
Depression and suicidal thoughts have occurred; the label advises watching mood and considering stopping if they appear.
Spontaneous erections in males and sexual side effects in females; an erection lasting over 4 hours needs emergency care.
In hypothalamic obesity: serious adrenal crises (5% vs 0% on placebo) and blood sodium swings in people with diabetes insipidus.
Serious allergic reactions, including anaphylaxis, have been reported. Not for common obesity, where the label says it isn’t expected to work.

Questions

What is setmelanotide?

How does setmelanotide work?

Setmelanotide is an eight-amino-acid ring-shaped peptide that switches on the melanocortin 4 (MC4) receptor, a brain receptor in the leptin pathway that controls hunger, fullness and energy use. POMC, PCSK1 or LEPR defects, Bardet-Biedl syndrome and hypothalamic damage weaken signaling to it, and based on animal and lab work the label says setmelanotide may restore it, cutting food intake and raising energy use. It is 20 times weaker at MC1, the pigment-cell receptor, yet still darkens skin. The label calls the pathway effect nonclinical (animal and lab evidence). Why responses vary between conditions, its long-term effects in young children, and any melanoma risk from its pigment effect are unknown.

Is setmelanotide FDA-approved?

Approved in the US as Imcivree: November 2020 for obesity from POMC, PCSK1 or LEPR deficiency confirmed by genetic testing, June 2022 for Bardet-Biedl syndrome (both now from age 2), and March 19, 2026 for acquired hypothalamic obesity from age 4. Also approved in the EU (2021), the UK and Canada, and in Japan for hypothalamic obesity (August 2026).

What is the usual setmelanotide dose?

From the label (Imcivree): Acquired hypothalamic obesity, adults: 0.5 mg once daily for 2 weeks, then 1 mg (weeks 3–4), 2 mg (weeks 5–6) and 3 mg from week 7, each step only if tolerated. Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency, adults: 2 mg once daily for 2 weeks, then 3 mg. If 2 mg isn’t tolerated, 1 mg for at least a week first; if 3 mg isn’t tolerated, back to 2 mg. These are the amounts sources reference, not recommendations.

How is setmelanotide given?

Drawn up with a 1 mL syringe and injected under the skin once daily by the patient or a trained caregiver. At the beginning of the day, with or without food.

Who should avoid setmelanotide?

Serious allergy to setmelanotide: Ruled out after a prior serious reaction, including anaphylaxis, to setmelanotide or any ingredient. History of depression or suicidal thoughts: These may recur on treatment. The label says to watch mood and consider stopping with suicidal thoughts or lasting depression. Many moles or past melanoma: Not ruled out, but it darkens existing moles and causes new ones; the label requires full-body skin exams before and during treatment. It doesn’t address melanoma history. The “Who should avoid it” section lists 4 more groups and one interaction.

What is the half-life of setmelanotide?

About 11 hours, according to the prescribing information. Effective half-life with daily 3 mg injections under the skin in adults; levels peak about 8 hours after a dose and reach steady state within 2 days. About 39% leaves unchanged in urine.

How should setmelanotide be stored?

Not a powder: a ready-made solution in a multiple-dose vial. Unopened: refrigerate at 2–8 °C in the carton until the expiry date, or keep at 2–25 °C for up to 30 days. After the first puncture, keep in the carton in the fridge or at up to 25 °C (brief excursions to 30 °C) and discard after 30 days.

Is setmelanotide banned in sport?

No. Not named on the 2026 list; it isn’t a corticotrophin (S2.2.2) or another listed peptide hormone, and S0 doesn’t apply to an approved drug.

Has setmelanotide been studied in people?

Yes. The human studies section lists 5 published studies. The largest, from 2026, included 120 people. BMI fell 16.5% vs a 3.3% rise on placebo in people aged 4 to 66, and hunger scores fell more; serious adverse events 28% vs 8%.

How long has setmelanotide been studied in people?

Trial 245 people across 5 trials were treated for at least 52 weeks (label); a long-term extension of 205 people ran from 2018 to January 2025.

Does setmelanotide come in other forms, like a pill or nasal spray?

Trial Only a daily injection under the skin is approved. A once-weekly injectable form was compared with the daily one in a phase 3 crossover trial but isn’t approved.

Can you drink alcohol while taking setmelanotide?

Precaution The label doesn’t address alcohol, and no interaction is known. Alcohol can worsen low mood, and depression is a label warning.

Can setmelanotide be taken with semaglutide or tirzepatide?

No study No study has combined it with a GLP-1 drug, and neither label addresses the pairing. Both commonly cause nausea and vomiting.

What happens if you take too much setmelanotide?

Label The US label advises supportive care; the UK label says overdose may cause nausea and erections, with blood pressure and heart rate watched for 48 hours. Call Poison Help (1-800-222-1222), or emergency services for severe symptoms.

Sources

Imcivree prescribing information, rev. 03/2026 (Rhythm Pharmaceuticals, DailyMed)
Drugs@FDA: Imcivree (NDA 213793), approved November 25, 2020; Bardet-Biedl syndrome June 16, 2022; acquired hypothalamic obesity March 19, 2026
Imcivree UK summary of product characteristics (Rhythm Pharmaceutical UK, rev. August 2026)
Miller et al., TRANSCEND trial in acquired hypothalamic obesity (NEJM 2026) PMID 42418774
Clément et al., phase 3 trials in POMC and LEPR deficiency (Lancet Diabetes Endocrinol 2020) PMID 33137293

For the protocol details

Imcivree prescribing information, rev. 03/2026, sections 2, 5, 6, 12 and 14 (DailyMed)
Imcivree UK summary of product characteristics, sections 4.2, 4.4 and 4.8 (rev. August 2026)

For how it works, who should avoid it and the limits of the evidence

Imcivree prescribing information, sections 4, 5, 8, 12 and 14 (Rhythm Pharmaceuticals, DailyMed, rev. 03/2026)
Imcivree UK summary of product characteristics, sections 4.4, 4.5 and 4.6 (rev. August 2026)
Haqq et al., phase 3 trial in Bardet-Biedl and Alström syndromes (Lancet Diabetes Endocrinol 2022) PMID 36356613

For uses, the side-effect questions, special situations, trials, identifiers and status outside the US

Imcivree prescribing information, sections 1, 2, 5, 6, 8, 10, 12, 13 and 14 (Rhythm Pharmaceuticals, DailyMed, rev. 03/2026)
Imcivree UK summary of product characteristics, sections 4.1, 4.4, 4.6, 4.8 and 4.9 (Rhythm Pharmaceutical UK, rev. August 2026)
Drugs@FDA: Imcivree (NDA 213793) original approval November 25, 2020, and supplements of June 16, 2022, December 20, 2024 and March 19, 2026
EMA medicines data for Imcivree: authorized July 16, 2021; Commission decision April 30, 2026 (acquired hypothalamic obesity)
Health Canada regulatory decision summary for Imcivree (decision May 5, 2023) and Drug Product Database entry DIN 02537745 (checked October 8, 2026)
Rhythm Pharmaceuticals announcements: EMANATE topline results (March 16, 2026), Japan approval (August 24, 2026) and Health Canada approval for hypothalamic obesity (September 22, 2026)
Kievit et al., MC4R agonist BIM-22493 in obese rhesus macaques (Diabetes 2013) PMID 23048186
Phase 2 trial of RM-493 in obesity, posted results (US trial registry entry) NCT01749137
Phase 3 crossover trial of daily and weekly setmelanotide (US trial registry entry) NCT05194124
FDA Global Substance Registration System records and WHO ATC index entry for setmelanotide
TGA product information search (checked October 8, 2026) and ClinicalTrials.gov registry entries for the trials listed

By Vial Guide editorsLast reviewed October 7, 2026

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