The New England Journal of MedicineTrial of Lixisenatide in Early Parkinson’s Disease

Lixisenatide’s Impact on Parkinson’s Disease Progression: Insights from a Phase 2 Trial

In a rigorously conducted phase 2 trial, researchers evaluated the efficacy of lixisenatide, a glucagon-like peptide-1 receptor agonist, in slowing the progression of motor disability in early Parkinson’s disease patients. The study’s design and its findings contribute valuable insights into the potential repurposing of diabetes medications for neurodegenerative disorders, offering a new perspective on treatment strategies.

Key Points:

• The study was a phase 2, double-blind, randomized, placebo-controlled trial aimed at assessing lixisenatide’s impact on Parkinson’s disease progression.
• Participants were individuals diagnosed with Parkinson’s disease less than 3 years earlier, on stable medication doses, without motor complications.
• They were randomized to receive either daily subcutaneous lixisenatide or a placebo for 12 months, followed by a 2-month washout period.
• The primary endpoint was the change in the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III scores at 12 months.
• At baseline, MDS-UPDRS part III scores were roughly 15 in both groups.
• After 12 months, the lixisenatide group showed a slight improvement (-0.04 points), while the placebo group experienced worsening (3.04 points), marking a significant difference between the groups.
• Two months post-treatment, the lixisenatide group continued to show less motor disability progression compared to placebo.
• Secondary endpoints, such as other MDS-UPDRS subscores and levodopa equivalent doses, did not show significant differences between groups.
• Nausea was reported by 46% of lixisenatide recipients, and vomiting occurred in 13%, indicating notable gastrointestinal side effects.
• The study reinforces the need for longer and larger trials to fully ascertain lixisenatide’s long-term effects and safety in Parkinson’s disease management.

In recent years, evidence has been proposed that GLP-1R agonists exert neuroprotective effects through modulating inflammation, oxidative stress, and mitochondrial dysfunction.

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