Exenatide does not slow Parkinson’s disease progression compared to placebo

1. There was no significant difference in functional outcome between both groups at 96 weeks.

2. Exenatide was safe and well-tolerated compared to placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: GLP-1 receptor agonists have shown neuroprotective effects in laboratory models of Parkinson’s disease. However, it remains unclear whether these medications can modify the course of the disease in clinical practice. This randomized controlled trial aimed to assess whether the GLP-1 receptor agonist, exenatide, could slow disease progression in patients with Parkinson’s disease. The primary outcome of this study was change in the Movement Disorder Society sponsored version of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score off dopaminergic medication at 96 weeks, while key secondary outcome was safety and tolerability. According to study results, there was no significant difference in motor symptom progression between the exenatide and placebo groups. Although this study was well done, it was limited by the lack of biomarker assessments to confirm drug target engagement, which may have influenced the observed outcomes.

Click to read the study in The Lancet

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In-depth [randomized controlled trial]: Between Jan 23, 2020, and Apr 23, 2022, 215 patients were screened for eligibility across 6 hospitals in the UK. Included were patients ≥ 25 years with Parkinson’s disease at Hoehn and Yahr stage ≤ 2.5 while on dopaminergic treatment. Altogether, 194 patients (97 to exenatide and 97 to placebo) were included in the final analysis. The primary outcome of change in MDS-UPDRS Part III scores at 96 weeks showed no significant difference between the exenatide and placebo groups (5.7 points vs. 4.5 points, adjusted coefficient for effect of exenatide 0.92, 95% confidence interval [CI] -1.56 to 3.39, p=0.47), indicating no effect on disease progression. Exenatide was well tolerated, with similar rates of serious adverse events between groups (9% vs. 11%). Findings from this study suggest that while exenatide is safe for Parkinson’s disease, it does not provide disease-modifying benefits.

Image: PD

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