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Home/Compounds/Setmelanotide
OtherFDA approvedRx required

Setmelanotide

Also known as: Imcivree · RM-493
Brands: Imcivree

MC4 receptor agonist approved for obesity due to POMC, PCSK1, LEPR, and Bardet-Biedl syndrome deficiencies.

A
Grade A
Multiple human RCTs
Human studies27
PubMed citations29
Routesubcutaneous
Regulatory (US)FDA approved · Rx
Last verified2 days ago

Mechanism of action

Cyclic heptapeptide melanocortin-4 receptor (MC4R) agonist. Restores downstream MC4R signaling in patients with specific upstream genetic defects in the leptin-melanocortin pathway.

Evidence summary

27
Human studies
29
PubMed citations
25
Clinical trials
A
Evidence grade

Evidence summary in progress. See the citations section below for the underlying research papers.

Dosing protocols

Educational information only. Consult a licensed provider before using any peptide.
Administration routes
subcutaneous

Side effects & safety

From the FDA label
Source
abdominal paindiarrheaheadachenauseavomiting

Terms pulled directly from the referenced source. We don't fabricate frequencies — when a label doesn't publish a percentage, we don't either.

Interactions

No documented drug interactions on file.

Regulatory status

United States
FDA approved

FDA approved for chronic weight management in patients ≥2 years with POMC, PCSK1, LEPR, or Bardet-Biedl syndrome (Imcivree)

Compounding
Not permitted

Not available via 503A/503B compounding pharmacies.

Regulatory data last verified 4/19/2026

Clinical trials

NCT07496463Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)Not Yet Recruiting · Phase 2 · Pseudohypoparathyroidism Type 1a · n=1NCT06772597A Phase 2 Open-label Study of Setmelanotide in Patients With Prader-Willi SyndromeActive Not Recruiting · Phase 2 · Prader-Willi Syndrome · n=18NCT06760546A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic ObesityRecruiting · Phase 3 · Hypothalamic Obesity · n=39NCT05093634A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients With POMC/PCSK1, LEPR, NCOA1(SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor PathwayActive Not Recruiting · Phase 3 · Obesity · n=296NCT06596135Open-Label Extension Study of Setmelanotide in Patients With a Rare Genetic, Syndromic or Acquired Disease of the MC4R PathwayEnrolling By Invitation · Phase 3 · Obesity Associated With Defects in Leptin-melanocortin Pathway · n=30NCT05774756A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic ObesityActive Not Recruiting · Phase 3 · Hypothalamic Obesity · n=120NCT04963231A 2-Stage (Open-Label Followed by Randomized Double-Blind, Placebo-Controlled Stage), Phase 2 Trial of Setmelanotide in Patients With Specific Gene Variants in the Melanocortin-4 Receptor PathwayCompleted · Phase 2 · Genetic Obesity · n=164NCT03651765Long Term Extension Trial of Setmelanotide (RM-493) for Patients Who Have Completed a Trial of Setmelanotide for the Treatment of Obesity Associated With Genetic Defects Upstream of the MC4 Receptor in the Leptin-melanocortin PathwayCompleted · Phase 2 · Obesity Associated With Defects in Leptin-melanocortin Pathway · n=205NCT05812183The Effect of Gastric Sleeve-Induced Weight Loss on Shortness of Breath in Patients with Obesity: a Feasibility StudyWithdrawn · Phase 4 · DyspneaNCT04725240A Phase 2, Open-Label 20-Week Study to Evaluate the Safety and Efficacy of Setmelanotide in Subjects With Hypothalamic ObesityCompleted · Phase 2 · Hypothalamic Obesity · n=18NCT04966741A Phase 3 Multi-Center, 1-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of ObesityCompleted · Phase 3 · Bardet-Biedl Syndrome · n=12NCT05194124A Phase 3, Randomized, Double-Blind Trial of Two Formulations of Setmelanotide (Daily and Weekly) With a Crossover to Open-Label Once Weekly Setmelanotide in Patients With Specific Gene Defects in the Melanocortin-4 Receptor Pathway Who Are Currently on a Stable Dose of the Once Daily FormulationCompleted · Phase 3 · Bardet-Biedl Syndrome · n=19

Showing 12 of 25 indexed studies. View all on ClinicalTrials.gov →

Citations

PMID 40903014H&#xfc;hne T, Polichronidou IM et al. · Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome.The Journal of clinical endocrinology and metabolism (2026)HumanPMID 40897637Mifsud F, Chalopin S et al. · Real-World Efficacy and Safety of Setmelanotide in Adults With Monogenic or Syndromic Obesity: A Prospective Cohort Study.Obesity (Silver Spring, Md.) (2025)HumanPMID 40995421Fredrick TW, Camilleri M et al. · Pharmacotherapy for Obesity: Recent Updates.Clinical pharmacology : advances and applications (2025)HumanPMID 40422561Al Lawati A, Alhabsi A et al. · Current and Emerging Parenteral and Peroral Medications for Weight Loss: A Narrative Review.Diseases (Basel, Switzerland) (2025)HumanPMID 40555693Anastasilakis AD, Paccou J et al. · The effects of anti-obesity medications on bone metabolism: A critical appraisal.Diabetes, obesity &amp; metabolism (2025)HumanPMID 39891402Kahveci A, Kurt I et al. · Real-life experience on efficacy and safety of setmelanotide treatment in prepubertal children.European journal of endocrinology (2025)HumanPMID 40484968Finkelberg I, Polichronidou IM et al. · Patient and caregiver experiences with a patient-support program for setmelanotide treatment of patients with Bardet-Biedl syndrome.Orphanet journal of rare diseases (2025)HumanPMID 39919037Haqq AM, Poitou C et al. · Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome.The Journal of clinical endocrinology and metabolism (2025)HumanPMID 38321079Fox CK, Kelly AS et al. · Current and future state of pharmacological management of pediatric obesity.International journal of obesity (2005) (2025)HumanPMID 39526054Qamar S, Mallik R et al. · Setmelanotide: A Melanocortin-4 Receptor Agonist for the Treatment of Severe Obesity Due to Hypothalamic Dysfunction.TouchREVIEWS in endocrinology (2024)HumanPMID 38697184Roth CL, Scimia C et al. · Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial.The lancet. Diabetes &amp; endocrinology (2024)HumanPMID 38397265Kalinderi K, Goula V et al. · Syndromic and Monogenic Obesity: New Opportunities Due to Genetic-Based Pharmacological Treatment.Children (Basel, Switzerland) (2024)HumanPMID 38450938Roth CL, McCormack SE · Acquired hypothalamic obesity: A clinical overview and update.Diabetes, obesity &amp; metabolism (2024)HumanPMID 38383825Shoemaker A · Bardet-Biedl syndrome: A clinical overview focusing on diagnosis, outcomes and best-practice management.Diabetes, obesity &amp; metabolism (2024)HumanPMID 36992862Chakhtoura M, Haber R et al. · Pharmacotherapy of obesity: an update on the available medications and drugs under investigation.EClinicalMedicine (2023)HumanPMID 37191347Faccioli N, Poitou C et al. · Current Treatments for Patients with Genetic Obesity.Journal of clinical research in pediatric endocrinology (2023)HumanPMID 36608818Bailey CJ, Flatt PR et al. · An update on peptide-based therapies for type 2 diabetes and obesity.Peptides (2023)HumanPMID 37365323Sweeney P, Gimenez LE et al. · Targeting the central melanocortin system for the treatment of metabolic disorders.Nature reviews. Endocrinology (2023)HumanPMID 36768472Mahmoud R, Kimonis V et al. · Clinical Trials in Prader-Willi Syndrome: A Review.International journal of molecular sciences (2023)HumanPMID 37888071Ferraz Barbosa B, Aquino de Moraes FC et al. · Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis.Journal of personalized medicine (2023)Human

Showing 20 of 29 papers. View all on PubMed →