Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial.

Roth CL, Scimia C, Shoemaker AH, Gottschalk M, Miller J, Yuan G, Malhotra S, Abuzzahab MJ

The lancet. Diabetes & endocrinology30 Apr 2024Cited by 62 (Europe PMC)

PMID38697184DOI10.1016/s2213-8587(24)00087-1PepBankPUB-38697184

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study11

11 results from studies that gave the peptide. 11 results from people.

01HumanNon-randomized trialEfficacy outcome
In hypothalamic obesity, 16 of 18 setmelanotide recipients (89%) reduced BMI at least 5% at 16 weeks versus a historic rate below 5% (p<0·0001).
In plain wordsIn hypothalamic obesity, 89% receiving setmelanotide reduced BMI at least 5% at 16 weeks versus a historic response rate below 5%.
Peptide
Setmelanotide
Outcome
IncreaseBMI reduction at least 5%
Study
n = 18
Comparator
Historic control rate less than 5%
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Patients meeting primary endpoint
16 patients
Of 18 enrolled at 16 weeks
Primary endpoint response rate
89%
BMI reduction at least 5% after 16 weeks
Source sentences
Summary
Of 18 patients enrolled, 16 (89%) of 18 patients completed the study and met the primary endpoint of reduction in BMI of at least 5% from baseline after 16 weeks (p<0·0001).
3 context sentences(design, population, supporting numbers)
Summary · context
The primary endpoint was the proportion of patients with a reduction in BMI of at least 5% from baseline after 16 weeks, compared with a historic control rate of less than 5% in this population.
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718401
02HumanNon-randomized trialEfficacy outcome
In patients with hypothalamic obesity receiving setmelanotide, mean BMI decreased 15% (SD 10).
In plain wordsIn patients with hypothalamic obesity receiving setmelanotide, average BMI decreased 15%.
Peptide
Setmelanotide
Outcome
DecreaseMean BMI reduction
Study
n = 18
Outcome group
Body weight · Metabolic and weight
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Mean BMI reduction
15%
All patients
BMI reduction SD
10%
All patients
Source sentences
Summary
The mean reduction in BMI across all patients was 15% (SD 10).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718402
03HumanNon-randomized trialEfficacy outcome
In hypothalamic obesity, 89% of setmelanotide recipients had a clinically meaningful composite change (90% CI 69-98%, p<0·0001).
In plain wordsIn hypothalamic obesity, 89% of setmelanotide recipients met the combined clinically meaningful change measure.
Peptide
Setmelanotide
Outcome
Not applicableComposite clinically meaningful change
Study
n = 18
Outcome group
Body weight · Metabolic and weight
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Composite clinically meaningful change
89%
90% CI 69-98%, p<0·0001
Source sentences
Summary
A composite proportion of patients had a clinically meaningful change (89%, 90% CI 69-98%; p<0·0001),
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718403
04HumanNon-randomized trialSafety outcome
Nausea occurred in 61% of setmelanotide recipients with hypothalamic obesity.
In plain wordsNausea occurred in 61% of patients with hypothalamic obesity receiving setmelanotide.
Peptide
Setmelanotide
Outcome
Not applicableNausea
Study
n = 18
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Nausea
61%
Setmelanotide recipients
Source sentences
Summary
Frequent adverse events included nausea (61%), vomiting (33%), skin hyperpigmentation (33%), and diarrhoea (22%).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718407
05HumanNon-randomized trialSafety outcome
Vomiting occurred in 33% of setmelanotide recipients with hypothalamic obesity.
In plain wordsVomiting occurred in 33% of patients with hypothalamic obesity receiving setmelanotide.
Peptide
Setmelanotide
Outcome
Not applicableVomiting
Study
n = 18
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Vomiting
33%
Setmelanotide recipients
Source sentences
Summary
Frequent adverse events included nausea (61%), vomiting (33%), skin hyperpigmentation (33%), and diarrhoea (22%).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718408
06HumanNon-randomized trialSafety outcome
Skin hyperpigmentation occurred in 33% of setmelanotide recipients with hypothalamic obesity.
In plain wordsDarker skin occurred in 33% of patients with hypothalamic obesity receiving setmelanotide.
Peptide
Setmelanotide
Outcome
Not applicableSkin hyperpigmentation
Study
n = 18
Outcome group
Pigmentation · Skin and wound
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Skin hyperpigmentation
33%
Setmelanotide recipients
Source sentences
Summary
Frequent adverse events included nausea (61%), vomiting (33%), skin hyperpigmentation (33%), and diarrhoea (22%).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718409
07HumanNon-randomized trialSafety outcome
Diarrhoea occurred in 22% of setmelanotide recipients with hypothalamic obesity.
In plain wordsDiarrhoea occurred in 22% of patients with hypothalamic obesity receiving setmelanotide.
Peptide
Setmelanotide
Outcome
Not applicableDiarrhoea
Study
n = 18
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Diarrhoea
22%
Setmelanotide recipients
Source sentences
Summary
Frequent adverse events included nausea (61%), vomiting (33%), skin hyperpigmentation (33%), and diarrhoea (22%).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718410
08HumanNon-randomized trialEfficacy outcome
In hypothalamic obesity, 12 setmelanotide extension participants completing at least 12 months had mean BMI change of -26% (SD 12) from index baseline.
In plain wordsIn hypothalamic obesity, 12 patients receiving setmelanotide for at least 12 months had an average BMI decrease of 26% from index baseline.
Peptide
Setmelanotide
Outcome
DecreaseLong-term BMI change
Study
n = 12
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · At least 12 monthsAs given in this study (human).
Measurements
Mean BMI change
−26%
12 extension participants completing at least 12 months, from index baseline
BMI change SD
12%
12 extension participants completing at least 12 months
Source sentences
Summary
Of 14 patients who continued treatment in a long-term extension study (NCT03651765), 12 completed at least 12 months of treatment at the time of publication and had a mean change in BMI of -26% (SD 12) from index trial baseline.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718411
09HumanNon-randomized trialEfficacy outcome
Among setmelanotide recipients younger than 18 years with hypothalamic obesity, 92% reduced BMI Z score at least 0·2 points (68-100%, p<0·0001).
In plain wordsAmong younger patients with hypothalamic obesity receiving setmelanotide, 92% reduced BMI Z score by at least 0·2 points.
Peptide
Setmelanotide
Outcome
DecreaseBMI Z score reduction at least 0·2 points
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
BMI Z score responders
92%
Patients younger than 18 years, reduction at least 0·2 points
Source sentences
Summary
comprising a reduction in BMI Z score of at least 0·2 points for patients younger than 18 years (92%, 68-100%; p<0·0001)
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718404
10HumanNon-randomized trialEfficacy outcome
Among setmelanotide recipients aged 18 years or older with hypothalamic obesity, 80% lost at least 5% bodyweight (34-99%, p<0·0001).
In plain wordsAmong adults with hypothalamic obesity receiving setmelanotide, 80% lost at least 5% bodyweight.
Peptide
Setmelanotide
Outcome
DecreaseBodyweight reduction at least 5%
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Bodyweight responders
80%
Patients aged 18 years or older, reduction at least 5%
Source sentences
Summary
and reduction in bodyweight of at least 5% for patients aged 18 years or older (80%, 34-99%; p<0·0001).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718405
11HumanNon-randomized trialEfficacy outcome
Setmelanotide recipients aged 12 years or older with hypothalamic obesity had a mean hunger score reduction of 45%.
In plain wordsPatients aged 12 years or older with hypothalamic obesity receiving setmelanotide reported 45% less hunger on average.
Peptide
Setmelanotide
Outcome
DecreaseHunger score
Study
n: not reported in source
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Titrated to 3·0 mg once daily · subcutaneous · 16 weeksAs given in this study (human).
Measurements
Mean hunger score reduction
45%
Patients aged 12 years or older
Source sentences
Summary
Patients aged 12 years or older had a mean reduction in hunger score of 45%.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible patients were aged between 6 and 40 years with obesity and history of hypothalamic injury or diagnosis of a non-malignant tumour affecting the hypothalamus that was treated with surgery, chemotherapy, or radiation.
Summary · context
Setmelanotide was titrated up to a dose of 3·0 mg and administered subcutaneously once a day for a total duration of 16 weeks.
Report a problemFND-3869718406

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 2 completed · 2 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT04725240

Open-Label Study of Setmelanotide in Hypothalamic Obesity

Rhythm Pharmaceuticals, Inc.n = 187 Jun 2021 to 28 Jun 2022

Hypothalamic Obesity

Trial page ClinicalTrials.govUpdated 7 Feb 2025

CompletedPhase 2/3Results postedNCT03651765

Long Term Extension Trial of Setmelanotide

Rhythm Pharmaceuticals, Inc.n = 20515 Jul 2018 to 9 Jan 2025

Obesity Associated With Defects in Leptin-melanocortin Pathway

Trial page ClinicalTrials.govUpdated 31 May 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:36 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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