Evidence map›Paper›PMID 40727970›Full record

Trial reportAnnals of neurology2025

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

Nirosen Vijiaratnam, Christine Girges, Martin Wiegand, Claudia Ismail, Alexandra Lameirinhas, Alison Yarnall, Cameron Kirk, Silvia Del-Din, Lynn Rochester, Christopher Kobylecki and 20 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Nirosen VijiaratnamDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
Christine GirgesDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
Martin WiegandDepartment of Statistical Science, University College London, London, UK.
Claudia IsmailNIHR UCLH Clinical Research Facility, London, England, UK.
Alexandra LameirinhasNIHR UCLH Clinical Research Facility, London, England, UK.
Alison YarnallNewcastle NIHR BRC, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, England, UK.
Cameron KirkNewcastle NIHR BRC, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, England, UK.
Silvia Del-DinNewcastle NIHR BRC, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, England, UK.
Lynn RochesterNewcastle NIHR BRC, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, England, UK.
Christopher KobyleckiManchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Gareth AmblerDepartment of Statistical Science, University College London, London, UK.
Simon SkeneSurrey Clinical Trials Unit, University of Surrey. Guildford, Guildford, UK.ORCID 0000-0002-7828-3122
Henry HouldenNational Hospital for Neurology and Neurosurgery, London, UK.
Viorica ChelbanNational Hospital for Neurology and Neurosurgery, London, UK.ORCID 0000-0002-5817-6290
Amanda HeslegraveUniversity College London, UCL UKDRI, Dept of Neurodegenerative Diseases, Queen Square House, London, England, UK.
Wendy PhillipsCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Alan WhoneMovement Disorders Group, Bristol Brain Centre, Southmead Hospital, Bristol, UK.ORCID 0000-0002-8931-4422
Niall QuinnDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
Christian LambertDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
Charlotte DoreFunctional Imaging Laboratory, Department of Imaging Neuroscience, London, England, UK.
Huw R MorrisDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-5473-3774
Mathew H HorrocksEaStCHEM School of Chemistry, The University of Edinburgh, Edinburgh, UK.
Ji Eun LeeEaStCHEM School of Chemistry, The University of Edinburgh, Edinburgh, UK.
Judi O'ShaughnessyEaStCHEM School of Chemistry, The University of Edinburgh, Edinburgh, UK.
Yazhou LiIntramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Nigel H GreigIntramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Sonia GandhiDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.
Vincenzo LibriNIHR UCLH Clinical Research Facility, London, England, UK.
Dilan AthaudaThe Francis Crick Institute, London, England, UK.
Tom FoltynieDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK.ORCID 0000-0003-0752-1813

Funding

The Physical Biology of Neurodegeneration in Sporadic Amyotrophic Lateral Sclerosis/Frontotemporal DementiaR01NS127186 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOLT, LIAM J, PHATNANI, HEMALI · 2021 to 2025
$8.2M
NINDS NIH HHS R01 NS127186
6 · The paper itself

Abstract

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.

Indexed as

ExenatideMultiple System AtrophyNeuroprotective AgentsAgedDrug Administration ScheduleFemaleHumansMaleMiddle AgedQuality of LifeTreatment OutcomeExenatideNeuroprotective Agents

Identifiers

PMID40727970
PMCPMC12577669

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.