Lixisenatide Decreases Motor Disability Progression in Early Parkinson Disease

Lixisenatide vs placebo is associated with decreased motor disability progression at 12 months among patients with early Parkinson disease (PD), but these patients experienced gastrointestinal side effects, according to the findings of a study published in The New England Journal of Medicine.

Previous studies have reported that patients with diabetes who were treated with glucagon-line peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 inhibitors vs those who did not receive these treatments had a lower prevalence of PD. Lixisenatide is based on a naturally occurring GLP analog that has a 4-times greater affinity for GLP-1 receptor than human GLP-1.

Researchers conducted a phase 2, double-blind, randomized, placebo-controlled trial, LixiParK (ClinicalTrials.gov Identifier: NCT03439943), in France between 2018 and 2020. Patients (N=156) aged 40 to 75 with early PD were randomly assigned in a 1:1 ratio to receive 10 mg subcutaneous lixisenatide for 14 days followed by 20 mg lixisenatide (n=78; mean age, 59.5; men, 56%; body mass index [BMI], 25.6) or placebo (n=78; mean age 59.9; men, 62%; BMI, 25.8) in addition to current PD medications for 12 months. Patients self-administered assigned treatment 15 minutes before dinner each night.

The primary outcome was the change in Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III score from baseline.

Among the lixisenatide and placebo groups, 100% and 97% were receiving levodopa, 45% and 41% were receiving monoamine oxidase B inhibitors, and 69% and 78% were receiving dopamine agonist, respectively.

At the 12-month follow-up, patients who received lixisenatide had a 0.04 (95% CI, -1.62 to 1.54) point decrease in MDS-UPDRS part III scores compared with a 3.04 (95% CI, 1.46-4.62) point increase in those who received placebo. Compared between groups, lixisenatide significantly affected MDS-UPDRS part III scores (mean difference [MD], 3.08; 95% CI, 0.86-5.30 points; P =.007).

After a 2-month washout period, average MDS-UPDRS part III scores in the lixisenatide treatment arm were 17.7 (95% CI, 15.7-19.7) points compared with 20.6 (95% CI, 18.5-22.8) points in the placebo arm.

In a post-hoc subgroup analysis, the effect of lixisenatide on MDS-UPDRS part III scores was larger among patients younger than age 60 than those aged 60 and older (MD, 5.22 vs 1.00 points), respectively.

The change in levodopa daily dose was similar between the intervention and control cohorts (mean change, 35.8 vs 31.3 mg/day), respectively.

Compared with 32% of patients who received placebo, 71% of patients who received lixisenatide experienced a related or possibly related adverse event. The most common adverse events among the lixisenatide group were nausea (46%) and vomiting (13%).

This study was limited by its short duration and the lack of imaging outcomes.

“In a 12-month phase 2 trial, the subcutaneously administered GLP-1 receptor agonist lixisenatide modestly reduced motor disability progression in patients with early Parkinson’s disease as compared with placebo but had gastrointestinal side effects. Larger and longer trials are needed to determine the effect and safety of this agent in the treatment of Parkinson’s disease.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.