In a significant development for Parkinson's disease treatment, a phase 2 clinical trial has shown that the GLP-1 agonist lixisenatide may help slow disease progression, marking a potential shift from purely symptomatic treatments to neuroprotective therapies.
The LixiPark trial, which began in 2018, evaluated 156 Parkinson's patients whose symptoms were stabilized on standard antiparkinsonian medications. The study compared daily subcutaneous injections of lixisenatide against placebo, focusing on changes in motor function as measured by MDS-UPDRS III scores over a 12-month period.
Clinical Trial Results
Patients receiving lixisenatide maintained remarkably stable motor function, showing only a minimal decline of 0.04 points on the MDS-UPDRS III scale. In contrast, the placebo group experienced a more substantial 3.04-point deterioration. However, the treatment wasn't without challenges – nearly half of the patients reported gastrointestinal side effects, particularly nausea.
Trial leaders Professors Wassilios Meissner and Olivier Rascol from Toulouse University Hospital characterized the findings as "a significant step forward in the future management of the disease," emphasizing the importance of further validation to translate these results into clinical practice.
Scientific Context and Implications
The study's significance extends beyond its immediate findings. Professor Tom Foltynie of University College London, who wasn't involved in the research, noted that these results replicate earlier findings from a 2017 Lancet study examining another GLP-1 agonist, exenatide, in Parkinson's disease.
"This cumulative clinical data strongly supports the earlier laboratory and epidemiological data, that GLP-1 receptor stimulation in the brain has neuroprotective effects relevant to the neurodegenerative processes of Parkinson's," Foltynie explained.
Future Perspectives
While promising, the relatively modest effect size over 12 months suggests the need for longer-term studies to establish clinical meaningfulness. The Parkinson's research community awaits two-year data from a phase 3 trial of exenatide, expected later this year, which could provide crucial insights into the sustained effectiveness of GLP-1 agonists in Parkinson's disease.
Lixisenatide's ability to cross the blood-brain barrier distinguishes it from newer GLP-1 agonists like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound), which have limited central nervous system penetration. This characteristic could prove crucial for its potential role in treating neurodegenerative conditions.
