A Phase 2 Study Suggests Diabetes Treatment May Slow Progression of Motor Symptoms in Parkinson’s Disease
A study published last month in the New England Journal of Medicine evaluated lixisenatide, a GLP-1 receptor agonist approved by the FDA in 2016 to improve glycemic control in patients with type 2 diabetes, in patients with early Parkinson’s disease. Lixisenatide has previously demonstrated neuroprotective effects in a mouse model of Parkinson’s.
The Phase 2, randomized, double-blind, placebo-controlled LixiPark study enrolled 156 participants aged 40 to 75 years from the French Clinical Research Network for Parkinson’s Disease and Movement Disorders. All had been diagnosed with Parkinson’s in the previous three years. Participants were on a stable dose of dopaminergic medication for one month before receiving study medication and for the first six months of the study; dose adjustments were permitted after six months.
Patients were randomly assigned to lixisenatide or placebo, administered as a 20 μg daily subcutaneous injection for 12 months. The primary endpoint was change from baseline in Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III. Secondary endpoints included other subscales of the MDS-UPDRS and were evaluated at baseline, six months, 12 months, and after a two-month washout period at 14 months.
At 12 months, MDS-UPDRS scores decreased (indicating improvement) in the lixisenatide group by 0.04 points and increased in the placebo group by 3.04 points (∆3.08; 95% CI, 0.86 to 5.30; P=0.007). After the two-month washout period, the mean MDS-UPDRS part III score in the lixisenatide group remained lower at 17.7 (95% CI, 15.7 to 19.7) in the lixisenatide group, with a score of 20.6 (95% CI, 18.5 to 22.8) in the placebo group. Although not evaluated for statistical significance, this difference suggests that the effect may go beyond a short-term symptomatic benefit and raises the possibility of a longer-lasting disease modifying effect.
Adverse events were reported by 86% in the lixisenatide group vs 71% in the placebo group. Gastrointestinal side effects including nausea, vomiting, and gastroesophageal reflux were more common in the lixisenatide group.
The study authors note that the treatment effect was primarily driven by a worsening of motor symptoms in the placebo group and conclude that larger and longer studies will be needed to confirm the efficacy and safety profile of lixisenatide for the treatment of Parkinson’s disease.
“For 30 years, we have been trying to understand how to slow the decline associated with Parkinson’s disease over time. In this context, the positive results of the LixiPark phase 2 trial showing less progression of motor symptoms of Parkinson’s disease over a year constitute a significant step forward in the future management of the disease. We look forward to confirming these encouraging results in the future, in order to translate such findings into clinical practice,” said principal investigators Wassilios Meissner and Olivier Rascol.
