What is Setmelanotide?

An FDA-approved melanocortin-4 receptor agonist for rare genetic obesity (POMC, PCSK1, LEPR deficiency and Bardet-Biedl syndrome).

Setmelanotide in the library · Metabolic & Weight Peptides · Human Trials · What are peptides?

25 registered trials · 16 indexed papers · 32 human / 18 animal studies

From the PeptideWhiz library entry. "As described" sections summarize claims made in the sources; they are not PeptideWhiz endorsements.

What it is

Setmelanotide (Imcivree) is described as a cyclic peptide that activates the MC4 receptor in the brain's appetite pathway. It is approved for specific genetic forms of obesity confirmed by testing.

Mechanism (as described)

It restores signaling downstream of broken leptin-melanocortin genes, reducing hunger.

Evidence (as described)

Approval was based on trials in POMC/LEPR deficiency (Clément et al., 2020) and Bardet-Biedl syndrome (Haqq et al., 2022); a 2026 trial studied acquired hypothalamic obesity (Miller et al., N Engl J Med 2026).

Status

FDA-approved (Imcivree) for specific genetic obesities.

Registered human trials (25)

Trial	Phase	Status	Year	Enrolled
Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)	Phase 2	enrolling by invitation	2026	1
A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)	Phase 3	recruiting	2025	39
A Study of Setmelanotide in Patients With Prader-Willi Syndrome	Phase 2	active not recruiting	2025	18
Open-Label Extension Study of Setmelanotide	Phase 3	completed	2024	28
A Trial of Setmelanotide in Acquired Hypothalamic Obesity	Phase 3	active not recruiting	2023	143
Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity	Phase 4	recruiting	2023	200
Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity	Phase 3	completed	2022	12
An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS)		approved for marketing	2022
Open-Label Study of Setmelanotide in Hypothalamic Obesity	Phase 2	completed	2021	18
DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway	Phase 2	completed	2021	164
Study of Setmelanotide Effects on QTc (Corrected QT) Interval in Healthy Participants	Phase 4	completed	2021	77
EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway	Phase 3	completed	2021	296
Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway	Phase 3	completed	2021	19
A Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment	Phase 1	completed	2020	32
Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity	Phase 3	completed	2018	15
Long Term Extension Trial of Setmelanotide	Phase 2/Phase 3	completed	2018	205
Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity	Phase 3	completed	2018	52
Setmelanotide for the Treatment of Early-Onset Pro-Opiomelanocortin (POMC) Deficiency Obesity	Phase 3	completed	2017	15
Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity	Phase 2	completed	2017	213
Setmelanotide in a Single Patient With Partial Lipodystrophy	Phase 2	completed	2017	1
Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome	Phase 2	completed	2015	40
RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients	Phase 2	unknown	2015	10
Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients	Phase 1/Phase 2	completed	2014	99
Phase 2 Study to Evaluate Safety and Efficacy of RM-493 in Obese Participants	Phase 2	completed	2013	74
Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RM-493 Administered to Healthy, Obese, Non-diabetic Volunteers	Phase 1	completed	2012	57

Peer-reviewed studies (16)

Paper	Authors	Journal	Year	Type
Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants	Roth CL et al.	Frontiers in behavioral neuroscience	2026	Clinical Trial
Setmelanotide for the Treatment of Acquired Hypothalamic Obesity	Miller JL et al.	The New England journal of medicine	2026	Randomized Controlled Trial
Setmelanotide in Bardet-Biedl Syndrome: A 52-Week Comparison of Phase 3 Trial Participants With a Matched Registry Cohort	Argente J et al.	Obesity (Silver Spring, Md.)	2026	Clinical Trial, Phase III
Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome	Haqq AM et al.	The Journal of clinical endocrinology and metabolism	2025	Randomized Controlled Trial
Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial	Argente J et al.	The lancet. Diabetes & endocrinology	2025	Clinical Trial, Phase III
Monoallelic pathogenic variants in LEPR do not cause obesity	Delplanque J et al.	American journal of human genetics	2024	Clinical Trial, Phase III
Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial	Roth CL et al.	The lancet. Diabetes & endocrinology	2024	Clinical Trial, Phase II
Could setmelanotide be the game-changer for acquired hypothalamic obesity?	van Santen HM et al.	Frontiers in endocrinology	2023	Randomized Controlled Trial
Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results	Forsythe E et al.	Orphanet journal of rare diseases	2023	Clinical Trial, Phase III
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	Haqq AM et al.	The lancet. Diabetes & endocrinology	2022	Randomized Controlled Trial
Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency	Kühnen P et al.	Orphanet journal of rare diseases	2022	Clinical Trial, Phase III
A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway	Kanti V et al.	Skin pharmacology and physiology	2021	Clinical Trial, Phase II
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.	The lancet. Diabetes & endocrinology	2020	Clinical Trial, Phase III
MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency	Clément K et al.	Nature medicine	2018	Clinical Trial, Phase II
Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency	Collet TH et al.	Molecular metabolism	2017	Clinical Trial
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist	Kühnen P et al.	The New England journal of medicine	2016	Clinical Trial, Phase II

More cited research

Conditions researched

Related compounds

FAQ

What is Setmelanotide?

An FDA-approved melanocortin-4 receptor agonist for rare genetic obesity (POMC, PCSK1, LEPR deficiency and Bardet-Biedl syndrome).

How many registered human trials study Setmelanotide?

The PeptideWhiz trial index lists 25 registered trials for Setmelanotide, the most recent from 2026.

How much published research exists on Setmelanotide?

The PeptideWhiz paper index links 16 PubMed papers to Setmelanotide; by study type, 32 human and 18 animal studies.

Which conditions is Setmelanotide researched for?

Fat loss, obesity & body recomposition, High cholesterol and statins, Insulin resistance, prediabetes & type 2 diabetes, Kidney protection (CKD, diabetic kidney, lupus kidney).

Research and education only. Not medical advice. No dosing guidance. Data: ClinicalTrials.gov registry and PubMed via the PeptideWhiz index (204,289 studies).

Reported dosing ranges from research