Foltynie T et al. – This clinical trial evaluated the neuroprotective effects of exenatide, a glucagon–like peptide–1 (GLP–1) receptor agonist, in patients with Parkinson’s disease. In this study, exenatide displayed positive effects on off–medication motor scores with continuous effect observed beyond period of exposure; therefore, exenatide represents a new avenue in the treatment of Parkinson’s disease requiring further investigation.

Methods

• In this single–center, randomized, double–blind, placebo–controlled study, eligible patients (aged 25–75 years, had idiopathic Parkinson's disease, were on dopaminergic treatment with wearing–off effects, and were at Hoehn and Yahr stage ≤2.5 when on treatment) were randomized (1:1) to receive subcutaneous injections of either exenatide 2 mg or placebo once weekly for 48 hours, followed by a 12–week washout period
• The primary outcome of this study was adjusted difference in the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS–UPDRS) motor subscale (part 3) in the practically defined off–medication state at 60 weeks.

Results

• Out of 62 enrolled patients who were randomized, 31 in the exenatide group and 29 in the placebo group were included in the primary analysis.
• At week 60, the adjusted mean difference between the groups for off–medication scores on part 3 of MD–UPDRS was –3.5 points (–6.7 to –0.3; P = .0318). The scores improved by 1.0 points (95% CI –2.6 to 0.7) in the exenatide group and worsened by 2.1 points (–0.6 to 4.8) in the placebo group.
• Commonly reported adverse events in both groups were injection site reactions and gastrointestinal symptoms.
• Although not assessed as related to study interventions, 6 and 2 serious adverse events were reported in the exenatide group and placebo group, respectively.