Exenatide Once Weekly in the Treatment of Patients with Multiple System Atrophy.

Vijiaratnam N, Girges C, Wiegand M, Ismail C, Lameirinhas A, Yarnall A, Kirk C, Del-Din S, Rochester L, Kobylecki C, Ambler G, Skene S and 18 more

Show all authors

Houlden H, Chelban V, Heslegrave A, Phillips W, Whone A, Quinn N, Lambert C, Dore C, Morris HR, Horrocks MH, Lee JE, O'Shaughnessy J, Li Y, Greig NH, Gandhi S, Libri V, Athauda D, Foltynie T

Annals of neurology29 Jul 2025Cited by 6 (Europe PMC)

PMID40727970PMCIDPMC12577669DOI10.1002/ana.70004PepBankPUB-40727970

Download PDF PubMedAsk about this study

Jump to 6 results

Summary

ObjectiveExenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of multiple system atrophy (MSA). We investigated these effects in a proof-of-concept clinical trial.MethodsIn this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period. The primary outcome was the Unified Multiple System Atrophy Rating Scale (UMSARS) parts I + II combined score at 48 weeks. Objective secondary outcome measures included the numbers of participants losing ambulation; scoring ≥ 3 on UMSARS part I items for falls, speech, swallowing, as well as timed walking and measures of quality of life and cognition.ResultsBetween September 23, 2020, and May 6, 2022, 50 participants were recruited (25 in each group). At 48 weeks, UMSARS parts I + II scores had worsened by 6.1 points (95% confidence interval [CI] = 3.0 to 9.3, SD = 6.9) in the exenatide group and by 13 3 points (95% CI = 9.2 to 17.3, SD = 9.4) in the control group, an adjusted mean difference of -7.4 points (-11.3 to -3.6, p = 0.0003). There were no statistically significant differences at either 48 or 96 weeks in the secondary outcome measures. Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha-synuclein oligomer load, sensor-derived gait measures, and imaging findings were also similar between groups.InterpretationExenatide was associated with positive effects on participant-reported symptoms and clinician-rated MSA severity. In contrast, none of the objective comparisons differed according to randomization. Given the open label trial design, the discrepancy between the primary outcome and the objective measures may be explicable as placebo effects/observer bias. ANN NEUROL 2025;98:991-1003.

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

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanRandomized controlled trialEfficacy outcome
In an open-label trial in participants with multiple system atrophy, UMSARS parts I + II scores worsened less with exenatide than with control at 48 weeks.
In plain wordsIn an open-label trial in people with MSA, symptom scores worsened less with exenatide than with control.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseUMSARS parts I + II combined score
Study
n = 50
Comparator
Control
Analysis
Primary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
2 mg weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Adjusted mean difference
−7.4 points
Exenatide versus control at 48 weeks
UMSARS parts I + II worsening
6.1 points
exenatide at 48 weeks
95% CI of adjusted mean difference
−11.3 to −3.6 points
exenatide versus control at 48 weeks
Source sentences
Summary
At 48 weeks, UMSARS parts I + II scores had worsened by 6.1 points (95% confidence interval [CI] = 3.0 to 9.3, SD = 6.9) in the exenatide group and by 13 3 points (95% CI = 9.2 to 17.3, SD = 9.4) in the control group, an adjusted mean difference of -7.4 points (-11.3 to -3.6, p = 0.0003).
1 context sentence(design, population, supporting numbers)
Summary · context
In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period.
Show in the study text Report a problemFND-4072797001
02HumanRandomized controlled trialEfficacy outcome
In participants with multiple system atrophy, secondary outcomes did not significantly differ between exenatide and control at 48 or 96 weeks.
In plain wordsIn people with multiple system atrophy, secondary outcomes did not significantly differ between exenatide and control.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeObjective secondary outcome measures
Study
n = 50
Comparator
Control
Analysis
Secondary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
2 mg weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
There were no statistically significant differences at either 48 or 96 weeks in the secondary outcome measures.
2 context sentences(design, population, supporting numbers)
Summary · context
Objective secondary outcome measures included the numbers of participants losing ambulation; scoring ≥ 3 on UMSARS part I items for falls, speech, swallowing, as well as timed walking and measures of quality of life and cognition.
Summary · context
In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period.
Show in the study text Report a problemFND-4072797002
03HumanRandomized controlled trialEfficacy outcome
In participants with multiple system atrophy, neurofilament light chain findings were similar between exenatide and control.
In plain wordsIn people with multiple system atrophy, nerve injury marker findings were similar with exenatide and control.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeNeurofilament light chain
Study
n = 50
Comparator
Control
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
2 mg weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha-synuclein oligomer load, sensor-derived gait measures, and imaging findings were also similar between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period.
Show in the study text Report a problemFND-4072797003
04HumanRandomized controlled trialEfficacy outcome
In participants with multiple system atrophy, CSF alpha-synuclein oligomer load findings were similar between exenatide and control.
In plain wordsIn people with multiple system atrophy, spinal fluid protein findings were similar with exenatide and control.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeCSF alpha-synuclein oligomer load
Study
n = 50
Comparator
Control
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
2 mg weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha-synuclein oligomer load, sensor-derived gait measures, and imaging findings were also similar between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period.
Show in the study text Report a problemFND-4072797004
05HumanRandomized controlled trialEfficacy outcome
In participants with multiple system atrophy, sensor-derived gait measures were similar between exenatide and control.
In plain wordsIn people with multiple system atrophy, sensor measurements of walking were similar with exenatide and control.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeSensor-derived gait measures
Study
n = 50
Comparator
Control
Outcome group
Exercise and physical function · Nervous system and cognition
Studied dose
2 mg weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha-synuclein oligomer load, sensor-derived gait measures, and imaging findings were also similar between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period.
Show in the study text Report a problemFND-4072797005
06HumanRandomized controlled trialEfficacy outcome
In participants with multiple system atrophy, imaging findings were similar between exenatide and control.
In plain wordsIn people with multiple system atrophy, scan findings were similar with exenatide and control.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeImaging findings
Study
n = 50
Comparator
Control
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
2 mg weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha-synuclein oligomer load, sensor-derived gait measures, and imaging findings were also similar between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period.
Show in the study text Report a problemFND-4072797006

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

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
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.