Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial.
Level 2 - randomized trial
Single-centre randomized, double-blind, placebo-controlled trial.
PubMed 28781108 · doi:10.1016/S0140-6736(17)31585-4
What was done
In a single-centre, double-blind, placebo-controlled trial, 62 patients aged 25–75 years with moderate idiopathic Parkinson's disease (Hoehn and Yahr stage ≤2.5 on dopaminergic treatment with wearing-off effects) were randomly allocated (1:1) to subcutaneous injections of exenatide 2 mg (n=32) or placebo (n=30) once weekly for 48 weeks, followed by a 12-week washout period. The primary outcome was the adjusted mean difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) evaluated in the practically defined off-medication state at 60 weeks. Analysis followed a modified intention-to-treat principle.
What was found
The primary analysis included 31 patients in the exenatide group and 29 in the placebo group. At 60 weeks (12 weeks post-treatment), off-medication MDS-UPDRS motor scores improved by 1.0 points (95% CI -2.6 to 0.7) in the exenatide group and worsened by 2.1 points (95% CI -0.6 to 4.8) in the placebo group, yielding a statistically significant adjusted mean difference of -3.5 points (95% CI -6.7 to -0.3; p=0.0318). Common adverse events in both groups included injection site reactions and gastrointestinal symptoms. Six serious adverse events occurred with exenatide and two with placebo; none were judged related to the interventions.
Why it matters
This trial shows that GLP-1 receptor agonist therapy can produce persistent motor score improvements after drug cessation in Parkinson's disease, supporting further investigation of potential neuroprotective effects.
Limits
The trial was conducted at a single centre with a small sample size (n=62 enrolled, 60 analysed). The 12-week washout is insufficient to definitively distinguish between disease modification and prolonged symptomatic relief, and long-term functional effects on everyday living were not established.
Cited by
- supports Emerging clinical evidence shows improvement in Parkinson's disease symptoms in patients taking GLP-1 receptor agonists.