Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome.

Hühne T, Polichronidou IM, Finkelberg I, Brensing P, Jaegers J, Dinkelbach L, Kiewert C, Galetzka W, Huessler EM, Scherer T, Bökenkamp A, Gäckler A, Pape L, Cetiner M

The Journal of clinical endocrinology and metabolism1 Feb 2026Cited by 2 (Europe PMC)

PMID40903014DOI10.1210/clinem/dgaf483PepBankPUB-40903014

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Summary

Background and objectiveThe melanocortin-4 receptor agonist setmelanotide compensates for upstream gene defects in the brain leptin-melanocortin pathway and reduces hyperphagia and obesity in selected monogenic obesity forms and Bardet-Biedl syndrome (BBS). We aimed to evaluate the short-term impact of setmelanotide treatment in BBS presenting original real-world data focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function.MethodsThis monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy. Ultrasound examination of the liver including shear wave elastography, dispersion and attenuation imaging (ATI), a bioimpedance analysis, and a hyperphagia questionnaire survey were applied in addition to clinical data collection.ResultsTwenty-six patients with BBS (mean age 19.2 years, range [6.2; 51.8]; mean body mass index (BMI) z-score 2.95, range [1.32; 4.84]) were included. All were classified with MASLD (54% S3, 23% each S1 and S2). After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1 mL/min/1.73 m² (95% confidence interval (CI) [4.3; 15.9]). The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]). A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1. MASLD improvement correlated only with liver size, not BMI reduction.ConclusionSetmelanotide treatment is associated with improvement of MASLD independent of BMI reduction as well as increased glomerular filtration rate in BBS.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanObservational studyEfficacy outcome
In BBS patients, setmelanotide treatment was associated with an eGFR increase up to 10.1 mL/min/1.73 m² (95% CI 4.3 to 15.9).
In plain wordsIn BBS patients, setmelanotide treatment was linked to increased estimated kidney filtration.
Peptide
Setmelanotide
Outcome
IncreaseEstimated glomerular filtration rate
Study
n = 26
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
eGFR change
≤ 10.1 mL/min/1.73 m²
6 months of setmelanotide
eGFR change 95% CI
4.3 to 15.9 mL/min/1.73 m²
6 months of setmelanotide
Source sentences
Summary
After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1 mL/min/1.73 m² (95% confidence interval (CI) [4.3; 15.9]).
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301401
02HumanObservational studyEfficacy outcome
In BBS patients, setmelanotide treatment was associated with a BMI z-score change of -0.5 (95% CI -0.6 to -0.3).
In plain wordsIn BBS patients, setmelanotide treatment was linked to a lower BMI z-score.
Peptide
Setmelanotide
Outcome
DecreaseBMI z-score
Study
n = 26
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
BMI z-score change
−0.5 z-score
6 months of setmelanotide
BMI z-score change 95% CI
−0.6 to −0.3 z-score
6 months of setmelanotide
Source sentences
Summary
The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]).
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301402
03HumanObservational studyEfficacy outcome
In BBS patients, setmelanotide treatment was associated with a hyperphagia score change of -12.3 (95% CI -15.5 to -9.0).
In plain wordsIn BBS patients, setmelanotide treatment was linked to reduced excessive hunger.
Peptide
Setmelanotide
Outcome
DecreaseHyperphagia score
Study
n = 26
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Hyperphagia score change
−12.3 points
6 months of setmelanotide
Hyperphagia score change 95% CI
−15.5 to −9 points
6 months of setmelanotide
Source sentences
Summary
The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]).
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301403
04HumanObservational studyEfficacy outcome
In BBS patients, setmelanotide treatment was associated with a total body fat change of -3.1% (95% CI -5.7 to -0.5).
In plain wordsIn BBS patients, setmelanotide treatment was linked to less body fat.
Peptide
Setmelanotide
Outcome
DecreaseTotal body fat
Study
n = 26
Outcome group
Body composition · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Total body fat change
−3.1%
6 months of setmelanotide
Total body fat change 95% CI
−5.7 to −0.5%
6 months of setmelanotide
Source sentences
Summary
The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]).
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301404
05HumanObservational studyEfficacy outcome
In BBS patients, setmelanotide treatment was associated with an ATI change of -0.14 dB/cm/MHZ (95% CI -0.17 to -0.11).
In plain wordsIn BBS patients, setmelanotide treatment was linked to a lower liver attenuation imaging value.
Peptide
Setmelanotide
Outcome
DecreaseAttenuation imaging
Study
n = 26
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
ATI change
−0.14 dB/cm/MHZ
6 months of setmelanotide
ATI change 95% CI
−0.17 to −0.11 dB/cm/MHZ
6 months of setmelanotide
Source sentences
Summary
The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]).
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301405
06HumanObservational studyEfficacy outcome
In BBS patients receiving setmelanotide, 85% exhibited MASLD resolution or stabilization at grade S1.
In plain wordsIn BBS patients receiving setmelanotide, 85% had liver disease resolution or stabilization at grade S1.
Peptide
Setmelanotide
Outcome
Not applicableMASLD resolution or stabilization at S1
Study
n = 26
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Measurements
Patients with MASLD resolution or stabilization at S1
85%
setmelanotide-treated BBS patients
Source sentences
Summary
A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1.
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301406
07HumanObservational studyOther
In setmelanotide-treated BBS patients, MASLD improvement correlated with liver size.
In plain wordsIn BBS patients receiving setmelanotide, liver disease improvement was linked to liver size.
Peptide
Setmelanotide
Outcome
Direction not reportedMASLD improvement association with liver size
Study
n = 26
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
MASLD improvement correlated only with liver size, not BMI reduction.
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301407
08HumanObservational studyOther
In setmelanotide-treated BBS patients, MASLD improvement did not correlate with BMI reduction.
In plain wordsIn BBS patients receiving setmelanotide, liver disease improvement was not linked to BMI reduction.
Peptide
Setmelanotide
Outcome
No significant changeMASLD improvement association with BMI reduction
Study
n = 26
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
MASLD improvement correlated only with liver size, not BMI reduction.
1 context sentence(design, population, supporting numbers)
Summary · context
This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy.
Show in the study text Report a problemFND-4090301408

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

Registered trials1

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

1 trial · 1 ongoing · source ClinicalTrials.gov (opens in a new tab)

RecruitingPhase 4NCT07674290

Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity

Tom Hühnen = 2001 Jan 2023 to est. 31 Dec 2030

Bardet Biedl Syndrome (BBS) · Bardet Biedl Syndrome · Bardet-Biedl Syndrome (BBS) · Alstrom Syndrome

Trial page ClinicalTrials.govUpdated 29 Jun 2026

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.

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