Lixisenatide linked with moderate symptom improvement in early Parkinson's
Patients with early Parkinson's disease in France who were treated with a glucagon-like peptide-1 receptor agonist had better outcomes on a motor disability scale at month 12 compared with those on placebo.
Treatment with lixisenatide resulted in less progression of motor disability than placebo at 12 months among patients with early Parkinson's disease but was linked with gastrointestinal side effects, according to new results of a phase II trial.
To test lixisenatide's efficacy, 156 patients who had been diagnosed with Parkinson's less than three years earlier were randomized 1:1 to daily subcutaneous lixisenatide or placebo for 12 months, followed by a two-month washout period. All participants were receiving a stable dose of medications to treat symptoms and did not have motor complications.
Researchers measured participants' scores on the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability) at baseline, month 12, and month 14. The multicenter trial took place in France. Findings were published by the New England Journal of Medicine on April 3.
At baseline, MDS-UPDRS scores were approximately 15 in both groups. Scores changed by −0.04 point in the lixisenatide group and 3.04 points in the placebo group (difference, 3.08 points [95% CI, 0.86 to 5.30 points]; P=0.007) at month 12. At month 14, mean MDS-UPDRS motor scores in the off-medication state were 17.7 points (95% CI, 15.7 to 19.7 points) with lixisenatide and 20.6 points (95% CI, 18.5 to 22.8 points) with placebo. Side effects were more common in the lixisenatide group than the control group and included nausea (46% vs. 12%), vomiting (13% vs. 3%), and gastroesophageal reflux (8% vs. 1%, respectively). Five participants in each arm experienced serious adverse events, with only one event in each group considered to be treatment related. Results on secondary endpoints, including other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent, did not substantially differ between groups.
One limitation to the study is a lack of imaging biomarkers to monitor disease progression. Researchers also only tested one dose of the treatment, and other doses might have better or worse effects, they said.
Previous research has suggested lixisenatide may enhance synaptic dopamine levels that may lead to improved symptoms in Parkinson's disease. However, more research is needed to determine the treatment's mechanism of action and its efficacy and safety in patients, the authors concluded.