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
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 Study drugs were withdrawn after 48 weeks, and the final follow-up visit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 fe-
male, 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
“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 pathophysiol-ogy 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.” NR
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].
Exenatide Aids Motor
Function in Parkinson’s Disease
Compared with conventional dopaminergic drugs, exenatide may have a more
persistent effect on disease severity.