Trial of Lixisenatide in Early Parkinson's Disease.
Level 2 - randomized trial
Individual phase 2 randomized controlled trial
PubMed 38598572 · doi:10.1056/NEJMoa2312323
What was done
In a phase 2, double-blind, randomized, placebo-controlled trial, 156 adults diagnosed with Parkinson's disease within the past 3 years on stable medications and without motor complications were randomly assigned (1:1) to daily subcutaneous lixisenatide (n = 78) or placebo (n = 78) for 12 months, followed by a 2-month washout. The primary endpoint was change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor score in the on-medication state at 12 months. Secondary endpoints included other MDS-UPDRS subscores at 6, 12, and 14 months and levodopa-equivalent doses.
What was found
Baseline MDS-UPDRS part III scores were approximately 15 in both groups. At 12 months, MDS-UPDRS part III scores changed by -0.04 points with lixisenatide and +3.04 points with placebo (difference, 3.08; 95% CI, 0.86 to 5.30; P = 0.007). At 14 months (after 2-month washout), mean off-medication motor scores were 17.7 (95% CI, 15.7 to 19.7) for lixisenatide and 20.6 (95% CI, 18.5 to 22.8) for placebo. Other secondary endpoints did not differ substantially. Nausea occurred in 46% and vomiting in 13% of participants receiving lixisenatide.
Why it matters
This trial provides clinical evidence that GLP-1 receptor agonist therapy may slow motor disability progression in early Parkinson's disease.
Limits
The study was a phase 2 trial with a modest sample size (156 participants) and a short follow-up duration (12 months on treatment). It was limited to early-stage disease without motor complications, secondary endpoints showed no substantial differences, and gastrointestinal side effects were frequent.
Cited by
- supports Emerging clinical evidence shows improvement in Parkinson's disease symptoms in patients taking GLP-1 receptor agonists.