Weight & metabolism

Setmelanotide

Peptilex evidence grade ABCDEUpdated 19 Oct 2026 How grades work

Type: MC4 receptor agonist
Main use or focus: Obesity and hunger caused by specific rare genetic conditions or by hypothalamic damage (US)
Also known as: Imcivree

Key studies from the book

Phase 3, 21 people with POMC or LEPR deficiency, about one year; at least 10 percent weight loss in 8 of 10 and 5 of 11.
Clément K et al. – Lancet Diabetes & Endocrinology, 2020
Phase 3, 38 people with Bardet-Biedl or Alström syndrome, 52 weeks; 32.3 percent of patients aged 12 and older with Bardet-Biedl syndrome lost at least 10 percent.
Haqq AM et al. – Lancet Diabetes & Endocrinology, 2022
Phase 3 in acquired hypothalamic obesity, 52 weeks; body mass index down 16.5 percent versus up 3.3 percent on placebo; basis of the US approval in 2026.
TRANSCEND – New England Journal of Medicine, 2026

All key studies, risks and open questions are in the book.

Research at a glance

Publications by typePubMed, all years

All papers219

Human studies131

Animal studies only11

Randomized trials4

Meta-analyses & systematic reviews5

Source: PubMed and ClinicalTrials.gov via the Peptilex study database

Registered trials by phaseClinicalTrials.gov · name in study title

ongoing / startingcompleted / other

Phase 11

Phase 28

Phase 310

Phase 41

Other1

Source: PubMed and ClinicalTrials.gov via the Peptilex study database

Trial starts per yearClinicalTrials.gov · by start date (planned starts included)

2016

32018

12020

12022

12024

12026

Source: PubMed and ClinicalTrials.gov via the Peptilex study database

Go deeper

Full profile in the book

What it is, how it acts, the key studies, risks and open questions.

Peptilex – The Peptide Encyclopedia

34 peptides – from semaglutide to BPC-157 – in one book
An evidence grade (A–E) and the key studies for every peptide
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Registered trials

ClinicalTrials.gov · name in study title · ongoing first

Study	Phase	Status	Participants	Start
A Trial of Setmelanotide in Acquired Hypothalamic Obesity NCT05774756Rhythm Pharmaceuticals, Inc.	Phase 3	Running	143	Apr 2023
A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756) NCT06760546Rhythm Pharmaceuticals, Inc.	Phase 3	Recruiting	39	Sep 2025
A Study of Setmelanotide in Patients With Prader-Willi Syndrome NCT06772597Rhythm Pharmaceuticals, Inc.	Phase 2	Running	18	Mar 2025
Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a) NCT07496463Massachusetts General Hospital	Phase 2	Enrolling	1	Jul 2026
Study of Setmelanotide Effects on QTc (Corrected QT) Interval in Healthy Participants NCT05046132Rhythm Pharmaceuticals, Inc.	Phase 4	Completed	77	Aug 2021
EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway NCT05093634Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	296	Dec 2021
Long Term Extension Trial of Setmelanotide NCT03651765Rhythm Pharmaceuticals, Inc.	Phase 2/3	Completed	205	Jul 2018
Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity NCT03746522Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	52	Nov 2018
Open-Label Extension Study of Setmelanotide NCT06596135Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	28	Oct 2024
Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway NCT05194124Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	19	Dec 2021

Show 10 moreShow fewer

Study	Phase	Status	Participants	Start
Setmelanotide for the Treatment of Early-Onset Pro-Opiomelanocortin (POMC) Deficiency Obesity NCT02896192Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	15	Feb 2017
Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity NCT03287960Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	15	Jan 2018
Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity NCT04966741Rhythm Pharmaceuticals, Inc.	Phase 3	Completed	12	Mar 2022
Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity NCT03013543Rhythm Pharmaceuticals, Inc.	Phase 2	Completed	213	Feb 2017
DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway NCT04963231Rhythm Pharmaceuticals, Inc.	Phase 2	Completed	164	Nov 2021
Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients NCT02041195Rhythm Pharmaceuticals, Inc.	Phase 1/2	Completed	99	Jan 2014
Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome NCT02311673Rhythm Pharmaceuticals, Inc.	Phase 2	Completed	40	Mar 2015
Open-Label Study of Setmelanotide in Hypothalamic Obesity NCT04725240Rhythm Pharmaceuticals, Inc.	Phase 2	Completed	18	Jun 2021
Setmelanotide in a Single Patient With Partial Lipodystrophy NCT03262610Rhythm Pharmaceuticals, Inc.	Phase 2	Completed	1	Aug 2017
A Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment NCT04348175Rhythm Pharmaceuticals, Inc.	Phase 1	Completed	32	Jul 2020

Showing 20 of 21 matching registered studies. See all on ClinicalTrials.gov.

Latest key papers

PubMed · newest first

2026
Setmelanotide for the Treatment of Acquired Hypothalamic Obesity
Human RCTPhase 3Miller JL et al. · NEJMPMID 42418774
2026
A systematic literature review of economic evaluations of setmelanotide
Systematic reviewBelančić A et al. · European Journal of Clinical PharmacologyPMID 42008191
2026
Adverse event profile of setmelanotide in obesity: an integrated assessment and systematic review using disproportionality analysis, case reports and meta-analysis
Meta-analysisSridharan K et al. · Expert Opinion on Drug SafetyPMID 39924461
2025
Biallelic pathogenic variants in POMC can cause combined pituitary hormonal deficiency associated with severe obesity
Systematic reviewVitellius G et al. · European Journal of EndocrinologyPMID 40513101
2025
Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome
Human RCTPhase 3Haqq AM et al. · J Clin Endocrinol MetabPMID 39919037
2023
Could setmelanotide be the game-changer for acquired hypothalamic obesity?
Human RCTvan Santen HM et al. · Frontiers in EndocrinologyPMID 38239988
2022
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
Human RCTPhase 3Haqq AM et al. · Lancet Diabetes & EndocrinologyPMID 36356613
2022
A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis
Systematic reviewLee K et al. · General Hospital PsychiatryPMID 35863294

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