Diabetes drug potentially staves off Parkinson’s symptoms
Individuals with Parkinson’s disease of moderate severity experienced improvement in motor symptoms following 48 weeks of treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide, according to results of a small study.
“This is a very promising finding, as the drug holds potential to affect the course of the disease itself, and not merely the symptoms,” said study senior author Professor Thomas Foltynie from the University College London (UCL) Institute of Neurology, London, UK.
“This is the strongest evidence we have so far that a drug could do more than provide symptom relief for Parkinson’s disease,” he said.
In this single-centre, double-blind trial, 62 patients with moderate Parkinson’s disease were randomized to self-administer once-weekly subcutaneous doses of exenatide (2 mg, n=32, mean age 61.6 years) or placebo (n=30, mean age 57.8 years) in addition to their regular medications for 48 weeks, followed by 12 weeks off-medication.
At 60 weeks, patients on exenatide demonstrated an improvement in motor scores signified by a 1.0-point improvement on part 3 of the MDS-UPDRS* compared with a 2.1-point worsening of symptoms experienced by patients on placebo (adjusted mean difference, -3.5 points, 95 percent confidence interval, -6.7 to -0.3; p=0.0318). [Lancet 2017;doi:10.1016/S0140-6736(17)31585-4]
At 48 weeks, patients on placebo experienced a 1.7-point deterioration while those on exenatide experienced a 2.3-point improvement in MDS-UPDRS (between-group difference, -4.3 points; p=0.0026).
On-medication MDS-UPDRS part 1–4 scores were comparable between groups at both 48 and 60 weeks and there was no significant between-group difference pertaining to cognition, mood, dyskinesia, nonmotor symptoms, or quality of life.
After adjusting for levodopa equivalent dose (LED) differences from baseline, patients on exenatide had 3.6 and 4.4 points lower MDS-UPDRS part 3 off-medication scores at 60 and 48 weeks, respectively, compared with patients on placebo (p=0.0294 and 0.0023, respectively).
Frequency of adverse events (AEs) was comparable between groups and patients in both groups experienced weight loss (mean reduction of 2.6 vs 0.6 kg in the exenatide vs placebo group at 48 weeks). None of the eight serious AEs reported (six and two in the exenatide and placebo groups, respectively) were deemed study drug-related.
In a commentary, Drs Werner Poewe and Klaus Seppi from Medical University Innsbruck, Innsbruck, Austria cautioned that patients on exenatide were older, had higher MDS-UPDRS part 3 scores, lower LED, and bigger increases in concomitant dopaminergic therapy during the trial compared with those on placebo, all of which could have affected the findings. [Lancet 2017;doi:10.1016/S0140-6736(17)32101-3]
“The 12-week washout period might [also] have been too short to eliminate potentially long-lasting symptomatic effects of exenatide,” they said.
“Whether [exenatide] acts as a novel symptomatic agent, influences compensatory responses or behaviours, or has neuroprotective effects on underlying pathology is unclear … however, these results represent a major new avenue for investigation in the treatment of Parkinson’s disease,” said the researchers, who advocated further study into assessing the potential Parkinson’s disease-modifying effects of exenatide, as well as of other GLP-1 receptor agonists.