#AAN2022 – Liraglutide for Diabetes Aids Mobility, Daily Life in Phase 2 Trial

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by Marta Figueiredo, PhD |

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Treatment with liraglutide — approved to treat type 2 diabetes and obesity — improved non-motor function and the ability to perform daily life activities in people with Parkinson’s disease, according to initial top-line data from a Phase 2 trial.

The therapy, sold by Novo Nordisk under the brand names Victoza and Saxenda, works by activating glucagon-like peptide-1 receptor (GLP-1R) proteins to stimulate insulin production in the pancreas, and has been reported to promote effects that are neuroprotective.

These findings add to an increasing body of data highlighting the potential benefits of GLP-1R activators, or agonists, for Parkinson’s patients.

Trial data were presented in the poster “Liraglutide Improves Non-Motor Function and Activities of Daily Living in Patients with Parkinson’s disease: A Randomized, Double-Blind, Placebo-Controlled Trial” at the 2022 American Academy of Neurology Annual Meeting (AAN), held in Seattle, April 2–7, and virtually, April 24–26.

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“These results are an encouraging and critical step in our pursuit of therapies that slow or stop Parkinson’s progression,” Patrik Brundin, MD, PhD, a professor of neuroscience and the director of the Parkinson’s Disease Center at Van Andel Institute in Michigan, said in a press release

Both the Van Andel Institute and the U.K.’s Cure Parkinson’s funded the trial.

“We believe diabetes medications, such as liraglutide, hold particular promise and look forward to additional results from the trial,” added Brundin, who is also chair of Cure Parkinson’s International Linked Clinical Trials program, which aims to repurpose approved medications to treat Parkinson’s and supported the liraglutide study.

Additional trial results are expected later this year and in 2023.

Increasing evidence suggests that GLP-1R agonists, which can reduce appetite and help to control sugar levels in the body by promoting insulin production, may be potential therapies for Parkinson’s.

Previous studies showed that GLP-1R agonists have neuroprotective effects — resulting in motor and non-motor improvements in animal models of Parkinson’s —  and suggest that people taking such medications are at a lower risk of developing Parkinson’s.

In addition, data from a previous Phase 2 clinical trial (NCT01971242) showed that exenatide, a short-acting GLP-1R agonist sold as Byetta, was superior to a placebo at aiding motor function in Parkinson’s patients on standard therapy.

New AAN data concerned a primary analysis of an ongoing Phase 2 trial (NCT02953665) evaluating the safety and effectiveness of liraglutide, a long-acting GLP-1R agonist, against a placebo in 63 adults with Parkinson’s.

Participants, recruited at Cedars Sinai Medical Center in Los Angeles, were randomly assigned to self-administer under-the-skin injections of either liraglutide (42 patients) or a placebo (21 patients) once a day for one year, in addition to conventional therapy. Liraglutide was given at a dose of 1.2 or 1.8 mg, as tolerated.

The trial’s main goal is to assess changes in motor, non-motor, and cognitive symptoms using validated measures taken 12 hours after the last dose of Parkinson’s medication. Secondary goals include changes in life quality and the ability to perform daily activities.

A total of 12 people discontinued treatment before one year, with four of them having completed six-month assessments.

Results from 37 liraglutide-treated patients and 18 patients on a placebo showed that one year of treatment with liraglutide significantly eased non-motor symptoms and improved daily life activities relative to a placebo. 

No significant differences were reported for changes in motor and cognitive symptoms between the two groups. The researchers suggested this lack of benefit may be related to a strong placebo effect — a sense of benefit despite no active treatment — which is reported to be stronger with more invasive administrations, such as injections.

Compared with the placebo, liraglutide’s use was associated with a significant drop in body mass index (BMI; a ratio of weight to height) and average blood sugar levels, findings that are consistent with the known effects of GLP-1R agonists.

Patients on liraglutide also reported significant gains in mobility in their quality of life experiences, which were more pronounced than those reported by placebo group patients.

“Whether this is due to improvements in their BMI, or because of the effect of liraglutide on their Parkinson’s, requires further investigation,” Cure Parkinson’s stated in the release.

The therapy was generally safe and well-tolerated, with common side effects including injection site reactions and gastrointestinal symptoms. A total of 11 serious adverse events were reported, none of which was deemed related to treatment.

“Liraglutide improves critical features of PD [Parkinson’s disease], including non-motor symptoms and activities of daily living,” the researchers wrote.

“These results validate similar outcomes reported with other [GLP-1R] agonists in PD and offer new strategies to treat the constellation of PD symptoms,” they added.

Notably, other GLP-1R agonists are under study as potential Parkinson’s therapies in clinical trials.

Extended-release exenatide (brand name, Bydureon) is being evaluated in a Phase 3 trial in the U.K. (NCT04232969), while NLY01, Neuraly’s experimental long-acting GLP-1R agonist, is being tested in a Phase 2 trial (NCT04154072) that dosed its first patient in 2020.

Note: The Parkinson’s News Today team is providing coverage of the American Academy of Neurology (AAN) 2022 Annual Meeting. Go here to see the latest stories from the conference.