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Type 2 diabetes drug lixisenatide shows potential in slowing Parkinson’s disease progression

The glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, commonly used to treat type 2 diabetes, may slow the progression of Parkinson’s disease symptoms, research suggests.

Investigators evaluating lixisenatide reported less progression of motor disability over a 12-month period in patients taking the drug compared with placebo.

But writing in the New England Journal of Medicine, they said lixisenatide was associated with gastrointestinal side effects in the phase two study and longer and larger trials are now needed to determine the impact and safety of the drug.

It is the second trial of a GLP-1 RA diabetes drug to show an effect in Parkinson’s disease with a 2017 study reporting improvement in motor symptoms in patients taking exenatide.

A larger phase three trial of exenatide, led by UK researchers, is due to report later this year.

The latest study enrolled 156 people with early Parkinson’s disease and no motor complications. All of the patients were taking their usual medication, but half also had a daily injection of lixisenatide and half were given a placebo.

After a year, those given lixisenatide showed no progression of motor problems while those on placebo dropped around three points on the assessment scale – classed as a moderate difference but likely to be clinically meaningful.

The difference was still apparent two months after the trial stopped, the researchers said, suggesting a neuroprotective effect.

Gastrointestinal side effects occurred in more than half the participants receiving lixisenatide, and often led to the dose of the drug being halved, but nausea did not appear to be associated with the magnitude of effect of the drug, they said.

The UK researchers said the study was important given it supports what had previously been found with exenatide.

Professor Tom Foltynie, professor of neurology, at the University College London (UCL) Queen Square Institute of Neurology, said: ‘This cumulative clinical data therefore strongly supports the earlier laboratory and epidemiological data, that GLP1 receptor stimulation in the brain has neuroprotective effects relevant to the neurodegenerative processes of Parkinson’s disease.’

But he said the beneficial effects are likely to be restricted to those GLP1 receptor agonists that can cross the blood-brain barrier which ruled out liraglutide and semaglutide.

Yet it is still not clear whether the drugs simply improve dopaminergic signalling to provide symptom relief or have a neuroprotective effect.

‘Phase 3 trial data of the effects of two years exposure to exenatide in patients with Parkinson’s disease will hopefully address this question and will be available in the second half of 2024,’ Professor Foltynie added.

Professor Masud Husain, who co-leads the dementia research team at the University of Oxford, said the results around lixisenatide were ‘really encouraging‘ for people with Parkinson’s disease.

‘However, the findings do not provide conclusive evidence that the drug has a protective effect on the brain to effectively slow down disease progression. We also have to bear in mind the side effects. Nausea occurred in nearly half and vomiting in 13% of people on the medication.’

Last summer, machine learning models accurately predicted sub-types of Parkinson’s disease based on images of patient-derived stem cells.

A version of this article was originally published by our sister publication Pulse.