Clinical Edge

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Exenatide Effects in Patients with Parkinson Disease

Lancet; 2017 Oct 7; Athauda, Maclagan, et al

In patients with moderate Parkinson disease (PD), exenatide had positive effects on practically defined off-medication motor scores, a recent study found. The randomized, double-blind, placebo-controlled trial included patients (aged 25-75 years) with moderate PD randomly assigned 1:1 to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period, between June 18, 2014, and March 13, 2015. Primary outcome was the 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. Researchers found:

  • 62 patients were enrolled; 32 were randomly assigned to exenatide and 30 to placebo.
  • At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS improved by 1.0 points in the exenatide group and worsened by 2.1 points in the placebo group (adjusted mean difference, –3.5 points).
  • There were 6 serious adverse events in the exenatide group vs 2 in the placebo group.

Citation:

Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Lancet. 2017;390:1664-1675. doi:10.1016/S0140-6736(17)31585-4.

Commentary:

Currently, all treatments for Parkinson disease are symptom-based and do not modify the course of the disease. The hope has always been to find a disease-modifying agent that could slow progression of the disease as well as improve symptoms. This novel study, looking at a common medication for diabetes, suggests that GLP-1 receptor agonists, specifically exenatide, may provide this disease-modifying effect. This is early, exciting data, and further clinical studies will be needed to see if this effect is in fact what it appears to be in the early study, and if it slows the progression of disability in patients with Parkinson disease over the long-term. —Neil Skolnik, MD