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GLP-1 drug shows little benefit for people with Parkinson’s disease

The GLP-1 drug, exenatide, has no positive impact on the movement, symptoms or brain imaging of people with Parkinson’s disease, finds a new study led by UCL Queen Square Institute of Neurology researchers.

4 February 2025

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The world’s largest and longest trial of exenatide in people with Parkinson’s disease was funded by the National Institute for Health & Care Research (NIHR) with support for sub-studies from Cure Parkinson’s and Van Andel Institute.

For their research, published in The Lancet, the team designed a randomised controlled phase 3 trial to definitively determine whether exenatide use was associated with any benefit in people with Parkinson’s disease and if it led to a slower rate of progression of the illness, after smaller studies had suggested the drug may be helpful.

194 people with Parkinson’s disease participated in the trial across six research hospitals in the UK, including in London, Oxford, Plymouth, Salford and Edinburgh. They either used exenatide injections on a weekly basis, or a visually identical placebo.

The trial ran for 96 weeks and was double blind, meaning that neither the participants nor researchers knew who was receiving the real treatment or placebo.

At the end of the study period, the researchers found that there was no advantage at any point over the course of 96 weeks in the group using exenatide. And no benefits were shown in the objective examination of patients’ movements, their own reports of symptom severity, or imaging findings.

Lead author, Professor Thomas Foltynie (Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology) said: “The results of this trial have been eagerly anticipated and the negative results will be a major disappointment to patients affected by Parkinson’s disease and the Parkinson’s disease research community.”

GLP-1 drugs – such as semaglutide (Wegovy) and Ozempic - have become increasingly popular over recent years and there has been an enormous interest in their potential health benefits.

For example, semaglutide (Wegovy) can be used as a treatment for Type 2 diabetes alongside being a licensed weight loss drug.

Meanwhile, older members of the drug class – such as exenatide and lixisenatide – have also been shown to be capable of penetrating into the brain and previous small trials have suggested potential benefits to people with Parkinson’s disease.

Professor Foltynie added: “It is not yet clear whether there may be a subgroup of people with Parkinson’s disease who may get benefit from the use of exenatide. We will continue to scrutinise the data to see whether abnormal blood test results such as having ‘pre-diabetes’ might predict a better response to exenatide, and whether there were more of these people in the earlier, smaller trials in which we found positive overall effects.”

The trial was supported by the UCL Comprehensive Clinical Trials Unit (UCL CCTU), the National Institute for Health and Care Research (NIHR), UCLH Biomedical Research Centre and the NIHR UCLH Clinical Research Facility. The trial took place at the UCL Queen Square Institute of Neurology and the UCLH National Hospital for Neurology and Neurosurgery.

There was a high level of participant retention throughout the trial and the research team have confirmed high levels of compliance with the medication by the use of blood tests checking the levels of exenatide, so there can be a high level of confidence in the results.

Links

  • Nirosen Vijiaratnam, et al, “Exenatide once a week versus placebo as a potential disease modifying treatment for people with Parkinson’s disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial” . The Lancet. Available online 4th February 2025.   DOI : 10.1016/S0140-6736(24)02808-3
  • Professor Thomas Foltynie's academic profile

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  • Credit: CIPhotos on iStock

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