Setmelanotide

What Setmelanotide does

Setmelanotide lowers hunger through a brain pathway that helps control eating. Imcivree is approved for certain rare genetic forms of obesity and acquired hypothalamic obesity. Trials show meaningful weight loss in these selected groups, with variable responses. Skin darkening and stomach upset are common; mood, moles and endocrine problems need monitoring.

• Imcivree is approved for obesity caused by certain rare genetic conditions (BBS, or POMC, PCSK1 or LEPR deficiency), from age 2. (Drug label)
• Imcivree is also approved for acquired hypothalamic obesity, from age 4. (Drug label)
• In a randomized trial in acquired hypothalamic obesity, people had substantial drops in BMI and hunger. (Studied in a trial)
• In a small real-world study of adults, weight fell to 20% below their highest within the first year, and hunger dropped 62%. (Studied in a trial)

Uses in the sources

• FDA-approved for obesity due to BBS or POMC, PCSK1 or LEPR deficiency, age ≥2; genetic testing requirements depend on the diagnosis. (Drug label) (source)
• FDA-approved for acquired hypothalamic obesity, age ≥4, since March 2026. (Drug label) (source)
• Studied in general obesity, but the label excludes it. Results in rare obesity disorders do not establish routine weight-loss benefit. (Studied in a trial) (source)
• Other gene variants and syndromes remain investigational. EMANATE failed all four prespecified primary endpoints. (Studied in a trial) (source)
• Registered human studies also cover drug levels, kidney impairment, formulations, broader genetic groups and ongoing indications. Some have no posted results. (Studied in a trial) (source)

Setmelanotide dosage

Typical reported dose: Genetic obesity, age 12+: starts at 2 mg once daily

• FDA: genetic obesity, age 12+: 2 mg once daily, then 3 mg once daily once daily, under the skin. Drug label. Studied in: BBS or genetically confirmed POMC, PCSK1 or LEPR deficiency; age ≥12. (source)
• FDA: acquired hypothalamic obesity: 0.5 mg once daily, then 1 mg once daily, then 2 mg once daily, then 3 mg once daily once daily, under the skin. Drug label. Studied in: Acquired hypothalamic obesity; age ≥6 years. (source)
• FDA: genetic obesity, ages 6–11: 1 mg once daily, then 2 mg once daily, then 3 mg once daily once daily, under the skin. Drug label. Studied in: BBS or POMC, PCSK1 or LEPR deficiency; age 6 to <12. (source)
• FDA: young children, baseline weight 15 to <20 kg: 0.5 mg once daily once daily, under the skin. Drug label. Studied in: Baseline weight 15 to <20 kg; genetic obesity age 2–5, or acquired hypothalamic obesity age 4–5. (source)
• FDA: young children, baseline weight 20 to <30 kg: 0.5 mg once daily, then 1 mg once daily once daily, under the skin. Drug label. Studied in: Baseline weight 20 to <30 kg; genetic obesity age 2–5, or acquired hypothalamic obesity age 4–5. (source)
• FDA: young children, baseline weight 30 to <40 kg: 0.5 mg once daily, then 1 mg once daily, then 1.5 mg once daily once daily, under the skin. Drug label. Studied in: Baseline weight 30 to <40 kg; genetic obesity age 2–5, or acquired hypothalamic obesity age 4–5. (source)

These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.

Work out syringe units with the dosing calculator

How to store Setmelanotide

Comes as: Imcivree ready-to-use 10 mg/mL solution in a 1 mL multiple-dose vial..

Mixed with: None. The approved product is a ready-to-use solution; do not add bacteriostatic water..

Common vial sizes: 10 mg. Common water amounts: mL.

• 10 mg in 1 mL is the labeled vial, not a powder mixing recipe.
• EU/UK: do not freeze; after opening keep at 2–30°C for no more than 28 days.
• US label, section 2.5: for labeled 0.5–3 mg doses, use a 1 mL syringe with a 28- or 29-gauge needle suited for subcutaneous injection.
• EU, 0.25 mg (0.025 mL): use a 0.3 mL syringe with 0.5-unit (half-unit) increments and a 29–31-gauge, 6–13 mm needle. EMA Table 12.
• EU, 0.5–3 mg (0.05–0.3 mL): use a 1 mL syringe with 0.01 mL increments and a 28–29-gauge, 6–13 mm needle. EMA Table 12.
• Warm for about 15 minutes outside the refrigerator or gently roll between palms for 60 seconds.
• Inspect for particles or abnormal discoloration. Each injection needs a new sterile needle and syringe.
• No reliable noncommercial source established common powder vial sizes, water volumes or mixed-product shelf life.

Before mixing: Unopened vial: 2–8°C in its carton until expiry. Outside refrigeration, 2–25°C for up to 30 days; brief excursions to 30°C allowed. Discard above 30°C.

After mixing: US vial: after first puncture, discard after 30 days or at expiry, whichever comes first. EU/UK vial: discard 28 days after opening. No mixing is needed.

Setmelanotide side effects and risks

Reported side effects

• Darkening skin: POMC/LEPR/PCSK1: 78% of 27; BBS: 63% of 43; hypothalamic obesity: 58% vs 10% placebo., mild. Skin darkening often fades after stopping; changing moles still need review. (source)
• Injection-site reactions: 96% of 27 in genetic deficiency trials; 51% of 43 in BBS; 67% of 12 children ages 2–5., mild. Rotate sites and check persistent painful, hot or spreading redness. (source)
• Nausea: Genetic deficiency 56%; BBS 26%; hypothalamic obesity 55% vs 25% placebo., moderate. Dose escalation may need to pause or step back for intolerance. (source)
• Vomiting: Genetic deficiency 30%; BBS 19%; hypothalamic obesity 38% vs 19%; ages 2–5: 58%., moderate. Persistent vomiting needs prompt review, especially with adrenal insufficiency or diabetes insipidus. (source)
• Headache: Genetic deficiency 41%; hypothalamic obesity 37% vs 31% placebo., mild (source)
• Diarrhea: Genetic deficiency 37%; BBS 14%; ages 2–5: 25%., moderate. Check hydration and sodium risk when symptoms persist. (source)
• Constipation: Genetic deficiency 11%; hypothalamic obesity 12% vs 6% placebo., mild (source)
• New or darker moles: Genetic deficiency 19%; BBS 14%; hypothalamic obesity 15% vs 6% placebo; ages 2–5: 33%., moderate. Arrange a skin review for new or changing pigmented lesions. (source)
• Spontaneous erections: Genetic deficiency 23% of 13 males; BBS 25% of 20 males. Hypothalamic obesity label reports 7% vs 4% overall., moderate. An erection lasting more than 4 hours is an emergency. (source)
• Depression: 26% of 27 in the open label genetic deficiency safety cohort., serious. Report new or worsening depression promptly; prescriber may stop treatment. (source)
• Suicidal thoughts: The reported 11% concerns a 27 person cohort in the dossier. It is not an all patient incidence. Monitor new or worsening depression and suicidal thoughts., serious. Seek emergency help for suicidal thoughts or intent. (source)
• Acute adrenal insufficiency: In acquired hypothalamic obesity with secondary adrenal insufficiency: serious events 5% active vs 0% placebo., serious. Urgent care for severe weakness, persistent vomiting, fainting or low blood pressure. (source)
• Low or high sodium: In hypothalamic obesity with diabetes insipidus: low sodium 6% vs 2%; high sodium 5% vs 4%, active vs placebo., serious. Confusion, severe drowsiness or seizures need emergency care. (source)
• Severe allergic reaction: Anaphylaxis is reported after marketing; its frequency cannot be estimated., serious. Stop and get emergency help for breathing trouble, swelling or fainting. (source)

Stop and get help if

• Trouble breathing, swelling of lips or tongue, or fainting after injection: Stop injections and get emergency care for possible anaphylaxis.
• Erection lasting longer than 4 hours: Get emergency care now to prevent permanent injury.
• Suicidal thoughts, intent or severe new mood changes: Get urgent mental-health help; call emergency services for immediate danger.
• Severe weakness, persistent vomiting, fainting or very low blood pressure: With adrenal insufficiency, follow the prescribed emergency steroid plan and get emergency care.
• Confusion, severe drowsiness, seizures or severe headache with fluid changes: Get emergency care for possible dangerous sodium imbalance.
• New or rapidly changing mole, bleeding pigmented spot or unusual dark lesion: Arrange prompt clinical skin assessment; do not assume every change is harmless tanning.
• Low blood sugar that does not recover, confusion or collapse: Get urgent care for persistent low glucose; emergency help is needed for collapse or impaired awareness.

Who should avoid it

• pregnant: Label says discontinue when pregnancy is recognized unless benefits outweigh fetal risks; human pregnancy data are absent.
• breastfeeding: Use while breastfeeding is not recommended by the label; human milk and infant safety data are absent.
• tryingToConceive: This is a precaution. Discuss stopping before trying to conceive; an evidence-based washout interval is unknown.
• under18: This is an app rule; FDA approval includes ages ≥2 for genetic obesity and ≥4 for acquired hypothalamic obesity.
• melanomaOrAtypicalMoles: The US label calls for skin examinations before and during treatment and monitoring of pigmented lesions. Prior serious hypersensitivity is the formal contraindication.
• eatingDisorderHistory: This is a precautionary app rule, not a labeled contraindication.
• other: Prior serious allergy to setmelanotide or its ingredients is the labeled contraindication. Anaphylaxis has been reported.
• depressionOrSuicidalThoughts: Mood symptoms and suicidal thoughts may occur. Prior depression may raise recurrence risk; monitor during treatment.
• kidneyDisease: Severe kidney impairment needs a lower genetic-obesity dose; acquired hypothalamic obesity use is not recommended. Avoid in end-stage kidney disease.
• other: US label: not recommended at eGFR <15, or acquired hypothalamic obesity with eGFR 15–29. EU has a different kidney-impairment schedule.
• other: Acquired hypothalamic obesity with secondary adrenal insufficiency: serious acute adrenal insufficiency occurred in 5% active versus 0% placebo.
• other: Central diabetes insipidus can lead to dangerous sodium changes. Monitor sodium as fluid intake or hydration changes.
• diabetes: Reduced food intake may lower insulin needs. One insulin-treated patient had repeated glucose <50 mg/dL.
• liverDisease: EU label says do not administer with liver impairment. US label says effects on drug levels are unknown.
• testedAthlete: Setmelanotide is not named on the 2026 list. Confirm the product with the athlete’s anti-doping body; no drug-specific ruling was found.

Interactions

• Insulin and sulfonylureas: Less food and weight loss may lower dose needs. Hypoglycemia occurred with insulin in one published case; no formal interaction trial exists.
• Desmopressin for central diabetes insipidus: In hypothalamic obesity, fluid intake changes may alter sodium control. Monitor sodium and adjust diabetes-insipidus medicines when needed.
• Glucocorticoid replacement: Vomiting can prevent steroid absorption in adrenal insufficiency. Review sick-day dosing and emergency steroid plans with the endocrine team.
• Other melanocortin agonists: Same-pathway combination data are absent. Added nausea, pigmentation or prolonged erections are plausible; do not assume selective MC4R action prevents them.
• GLP-1 and other appetite-lowering medicines: TRANSCEND allowed stable background GLP-1 use; no dedicated combination trial was found. Added nausea and reduced intake may affect hydration and glucose control.
• Oral medicines and anticoagulants: No clinical interaction studies were done. A GLP-1-like delayed-stomach-emptying interaction or specific anticoagulant effect has not been established.

Product quality risks

• No independent setmelanotide-specific survey of online vial purity, sterility or dose accuracy was located.
• General FDA compounding evidence shows risks of contamination and too much or too little active ingredient; no setmelanotide-specific rate is known.
• An online powder or pen is not established as equivalent to the approved 10 mg/mL vial.
• A purity percentage alone cannot show identity, milligrams per vial, sterility or bacterial-toxin levels.

What to expect

At least 28 interventional study records, including ongoing studies; rare-obesity trials support approval. Case reports and secondary analyses overlap.

Key studies

• Energy use: 72-hour infusion: A short infusion raised resting energy use; it did not establish a general weight-loss regimen. (source)
• MC4R variants: early dose finding: Some MC4R variants responded, but this does not support all MC4R variants or general obesity. (source)
• First POMC patients: Two adults with POMC deficiency had large reductions in hunger and weight. (source)
• First LEPR patients: Three LEPR-deficient patients responded during roughly one year of follow-up. (source)
• POMC/PCSK1: pivotal trial: Weight loss varied by genetic defect; selected responders regained weight during placebo withdrawal. (source)
• LEPR: pivotal trial: Weight loss varied by genetic defect; selected responders regained weight during placebo withdrawal. (source)

Setmelanotide FAQ

• Is Setmelanotide FDA-approved? Yes: Imcivree (specific genetic obesity from age 2; acquired hypothalamic obesity from age 4.). Original approval 2020; BBS added 2022; genetic-obesity age 2 added 2024; acquired hypothalamic obesity added March 2026. General obesity is excluded.
• How do people take it? Under the skin, once daily. Source: drug label.
• What's the difference between Setmelanotide and Liraglutide? Setmelanotide: a daily injection approved for specific genetic obesity and acquired hypothalamic obesity. Liraglutide: a daily GLP-1 injection approved for weight management and type 2 diabetes. Why people pair them: one BBS case used these in sequence for appetite and weight. Liraglutide was stopped first; this was not a concurrent stack.
• Can I take it with Liraglutide followed by setmelanotide? One BBS case used these in sequence for appetite and weight. Liraglutide was stopped first; this was not a concurrent stack. One sequential case cannot establish safety or added benefit from taking both together. Source: clinician-published. Ask a doctor before combining anything.
• Is it banned in sport? It is unclear (WADA 2026). Setmelanotide and MC4R agonists are not named. S0 concerns unapproved drugs; setmelanotide has human approvals. Athlete-specific confirmation remains needed.
• How do I store it once opened? US vial: after first puncture, discard after 30 days or at expiry, whichever comes first. EU/UK vial: discard 28 days after opening. No mixing is needed.