Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-25. ← Back to Evidence Library

Setmelanotide: what the evidence says

At a glance

What it is: an injectable peptide that activates the brain's MC4 receptor, sold as Imcivree. It is FDA-labeled for obesity caused by certain rare conditions: Bardet-Biedl syndrome, POMC, PCSK1 or LEPR deficiency, and acquired hypothalamic obesity. ^R3 Gray-market sellers market it for general weight loss.

What the evidence says: in small phase 3 trials, 80% of people with POMC deficiency and 45% with LEPR deficiency lost at least 10% of body weight at about 1 year ^R1; in a placebo-controlled trial, 32% of people 12 and older with Bardet-Biedl syndrome did. ^R2 We found no evidence reviewed here for common obesity.

Biggest risks: skin darkening, spontaneous erections and sexual side effects, depression and suicidal thoughts, and serious allergic reactions are label warnings. ^R3 Injection-site reactions and nausea were common. ^{R1, R2}

Rating


Human Human evidence	Moderate for labeled rare genetic obesity ^{R1, R2}; No human data reviewed for common obesity or gray-market use [UNVERIFIED: early general-obesity trials not reviewed]
Animal Animal / lab evidence	Not reviewed for this page
Regulatory	FDA-approved (Imcivree, NDA 213793; label on DailyMed) ^R3 · other regulators UNVERIFIED · WADA: not named on the 2026 List ^R4
Established human dose	For labeled uses: on the FDA label ^R3; for other uses: none. Study details lists what trials used

Evidence verdict: Rare genetic obesity (labeled): Moderate · General or gray-market weight loss: No human data Card verdict: Moderate (approved use: rare genetic obesity) · General or gray-market weight loss: No human data Card note: Gray-market vials are not the approved product, see page.

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: both trials below were funded by the manufacturer, Rhythm Pharmaceuticals. ^{R1, R2}

What is it?

Setmelanotide is a synthetic peptide that activates the melanocortin-4 (MC4) receptor, part of the brain pathway that controls hunger. People with certain genetic defects in this pathway have extreme hunger and early, severe obesity. ^{R1, R2} It also activates the receptor that darkens skin, which is why skin darkening is common. Unknown Related pages: Melanotan II, Melanotan I, PT-141.

Does it work?

Human POMC and LEPR deficiency: single-arm phase 3 trials, 10 and 11 people: 80% and 45% lost ≥10% of body weight at about 1 year; hunger scores fell. ^R1
Human Bardet-Biedl and Alström syndromes: 38 patients, 14 weeks blinded then 52 weeks open-label: 32.3% of patients 12 and older with Bardet-Biedl lost ≥10%; results inconclusive for Alström. ^R2
Unknown Common obesity or gray-market use: not reviewed; no evidence cited here.

Is it safe?

Human Label warnings: spontaneous erections and sexual adverse reactions; depression and suicidal ideation; serious hypersensitivity including anaphylaxis; skin hyperpigmentation and darkening of existing moles. ^R3
Human In trials: skin darkening (61%) and injection-site redness (48%) ^R2; injection-site reactions in every participant, nausea and vomiting. ^R1
Unknown Long-term effects in people without these genetic conditions unknown.

Gray-market "research use only" Setmelanotide: extra risks

Not the approved product. Gray-market "setmelanotide" is not Imcivree; identity, strength and sterility are unknown. Unknown The label warnings (depression, suicidal thoughts, sexual effects) apply to any real setmelanotide, without the monitoring a prescriber provides. ^R3

What we don't know

Unknown Whether it helps common obesity
Unknown Long-term safety outside trial populations
Unknown What is in a gray-market vial

Is it legal?

US: FDA-approved as Imcivree (NDA 213793) for the uses on its label. ^R3 EU, UK and others: UNVERIFIED, not checked with EMA or MHRA. WADA: not named on the 2026 Prohibited List. ^R4 Whether any other WADA section applies has not been checked UNVERIFIED.

Study details

These are amounts researchers used, not recommendations.

R1 Human Phase 3 single-arm: POMC and LEPR deficiency (Clément 2020)

Study	People / model	Route	Amount used	Follow-up	Reported	Side effects / limitations	Citation
Clément 2020	10 POMC and 11 LEPR participants, age ≥6	Subcutaneous	Not in abstract	~1 year	80% and 45% lost ≥10%	Single-arm, small; sponsor-funded	PMID 33137293

R2 Human Phase 3 RCT: Bardet-Biedl and Alström (Haqq 2022)

Study	People / model	Route	Amount used	Follow-up	Reported	Side effects / limitations	Citation
Haqq 2022	38 patients, age ≥6	Subcutaneous	Up to 3.0 mg once daily	14 weeks blinded + 52 weeks open-label	32.3% (BBS, age ≥12) lost ≥10%	Small; Alström inconclusive; sponsor-funded	PMID 36356613

Full reference list (PubMed entries checked Oct 25, 2026)

^R1 Clément K, et al. 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. Lancet Diabetes Endocrinol. 2020. PMID 33137293
^R2 Haqq AM, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022. PMID 36356613
^R3 DailyMed. IMCIVREE (setmelanotide) label, Rhythm Pharmaceuticals, published Apr 2, 2026. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9
^R4 WADA. The 2026 Prohibited List (in force 1 January 2026). https://www.wada-ama.org/en/prohibited-list

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Setmelanotide. Talk to a clinician you trust before using any drug, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).

Approved for Adam Greene by Dr. Nova Reyes, 2026-10-25.