Exenatide Aids Motor Function in Parkinson’s Disease

Exenatide improves motor function in patients with Parkinson’s disease, according to research published online ahead of print August 3 in Lancet. The improvements may persist for months after treatment exposure.

Exenatide, an analogue of glucagon-like peptide-1, is used to treat type 2 diabetes. In rodent models of Parkinson’s disease, exenatide had neuroprotective effects and improved motor performance, behavior, learning, and memory. The drug also provided motor and cognitive benefits in a proof-of-concept study including patients with Parkinson’s disease.

Active Group Was Slightly Older

Dilan Athauda, MBBS, Senior Clinical Research Associate at University College London, and colleagues conducted a double-blind study to assess exenatide’s potential disease-modifying effects. At screening for study entry, patients with idiopathic Parkinson’s disease underwent physical and neurologic examinations, assessments of mood and cognition, and blood sampling. The investigators randomized eligible participants to subcutaneous injections of exenatide (2 mg) or placebo once weekly for 48 weeks. Participants continued to take their regular medications. Investigators examined patients in an off-medication state and collected blood and urine at baseline and weeks 12, 24, 36, and 48. Study drugs were withdrawn after 48 weeks, and the final follow-up visit was at week 60.

The primary outcome was change in Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3 score at 60 weeks. Secondary outcomes included differences between exenatide and placebo in each subsection of the MDS-UPDRS in the on-medication state, and the Mattis Dementia Rating Scale at weeks 48 and 60.

In all, 62 participants were randomized. Patients assigned to exenatide were slightly older, had higher baseline MDS-UPDRS part 3 scores, and had lower levodopa equivalent dose than did controls. Average age was about 62 in the exenatide group and about 58 among controls. About 26% of the population was female, and the mean disease duration at baseline was 6.4 years. Approximately 97% of the population were between Hoehn and Yahr stage 1 and 2 at baseline.

Exenatide Yielded Motor Improvement

At week 60, off-medication MDS-UPDRS part 3 scores had worsened by 2.1 points in the placebo group and improved by 1.0 point in the exenatide group, yielding a significant adjusted difference of –3.5 points. At week 48, scores among controls had deteriorated by 1.7 points, and those in the exenatide group had improved by 2.3 points, resulting in a significant adjusted between-group difference of –4.3 points.

On-medication scores on MDS-UPDRS parts 1 through 4 did not differ significantly between groups at weeks 48 or 60. The researchers also did not observe a significant difference between groups in Mattis Dementia Rating Scale score at those time points. The frequency of adverse events was similar between groups.

“Exenatide could have a longer-lasting effect on disease severity beyond conventional drug effects on dopaminergic receptors,” said the researchers. “Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson’s disease, and effects on everyday symptoms should be examined in longer-term trials.”

—Erik Greb

Suggested Reading

Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Aug 3 [Epub ahead of print].