# LIXIPARK Trial

**Type:** Phase 2 randomized controlled trial  
**Indication:** Early Parkinson's disease  
**Drug:** Lixisenatide (GLP-1 receptor agonist)  
**Status:** Completed, published NEJM April 2024  
**Primary endpoint:** MDS-UPDRS Part III motor score at 12 months — MET

## Design
- **N:** 156 patients (75 lixisenatide, 75 placebo; some sources report 150)
- **Population:** Early Parkinson's disease (<3 years since diagnosis)
- **Duration:** 12 months
- **Design:** Double-blind, placebo-controlled
- **Administration:** Daily subcutaneous injection

## Results
**Primary endpoint (12 months):**
- Placebo group: MDS-UPDRS Part III worsened by +3.04 points (disease progression)
- Lixisenatide group: Remained at baseline (0 change)
- Between-group difference: Statistically significant
- Interpretation: Lixisenatide halted motor symptom progression over 12 months

**Safety:**
- >50% of lixisenatide patients reported significant GI side effects (nausea, vomiting)
- >1/3 required dose reduction due to GI tolerability
- Safety profile is a major practical concern for real-world implementation

## Limitations
- Phase 2 (not Phase 3 — not definitive)
- 12 months (shorter than exenatide Phase 3 at 96 weeks)
- No DaT-SPECT brain imaging to confirm neuroprotection vs. symptomatic benefit
- Off-label use NOT recommended pending Phase 3 confirmation

## Context
- Preliminary results presented at 2023 International Parkinson and Movement Disorder Society congress (Copenhagen)
- Published NEJM April 2024
- As of May 2026, no Phase 3 funding announced despite positive Phase 2 result
- Contrasts with exenatide Phase 3 failure (Lancet February 2025)

## Mechanistic hypothesis
Lixisenatide crosses BBB via adsorption transcytosis (Holscher 2024). Holscher identifies lixisenatide as having "strongest neuroprotective effect" among GLP-1 agonists in clinical trials, correlating with BBB penetrance mechanism. The divergence from exenatide suggests regional CNS penetrance (specifically substantia nigra) may determine efficacy.

## Timeline
- **2023** — Preliminary results presented at International Parkinson and Movement Disorder Society congress, Copenhagen
- **2024-04-04** — Full results published in New England Journal of Medicine
- **2026-05** — No Phase 3 funding announced; exenatide Phase 3 failure may have chilled further GLP-1 Parkinson's investment