Diabetes med lixisenatide may slow motor decline in Parkinson’s: Study

Researchers call for more studies to confirm medication's effects on Parkinson's

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with lixisenatide, a medication approved for type 2 diabetes, significantly slowed the progression of motor symptoms in people with Parkinson’s disease in a Phase 2 clinical trial.

Although gastrointestinal side effects such as nausea and vomiting were more common with the therapy, the findings support lixisenatide as a potential treatment for Parkinson’s. Researchers are calling for more studies to confirm the medication’s effects.

Findings were published in The New England Journal of Medicine in a study, “Trial of Lixisenatide in Early Parkinson’s Disease.” The work was funded by the French Ministry of Health and Cure Parkinson’s in the U.K. with Van Andel Institute, and with drug and placebo support from pharmaceutical company Sanofi.

“I am thrilled to see the extremely positive, groundbreaking clinical outcome of the lixisenatide trial, which could have real meaning for people living with Parkinson’s,” Richard Wyse, MD, director of clinical development at Cure Parkinson’s, said in a press release.

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No approved treatments yet available to slow Parkinson’s progression

Although a number of treatments for Parkinson’s are available, they work to ease disease symptoms only. No therapy has ever been proven to actually slow the progression of Parkinson’s disease, at least not yet.

Lixisenatide belongs to a class of medications that activate the GLP-1 receptor, thereby increasing insulin and lowering glucose levels in people with diabetes. Findings from animal studies have suggested the drug may also have protective effects on brain cells, so it could potentially be beneficial in neurological disorders like Parkinson’s.

Another piece of evidence supporting that idea is the fact that people who take GLP-1 agonists for diabetes have a much lower incidence of Parkinson’s than those who receive other diabetes medications.

To explore the potential of lixisentatide in Parkinson’s, a team led by scientists in France conducted a Phase 2 trial called LixiPark (NCT03439943), which enrolled 156 people who had been diagnosed with Parkinson’s in the prior three years.

Participants were randomly assigned to receive lixisenatide or a placebo, on top of their current Parkinson’s medications, for one year. Treatment was given daily via subcutaneous (under-the-skin) injections, about 15 minutes before dinner.

For those on lixisenatide, the drug was started at a dose of 10 micrograms, then increased to 20 micrograms after the first two weeks if tolerated.

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Study to assess effect of lixisenatide on severity of motor symptoms

The study’s main goal was to assess the effect of treatment on the severity of motor symptoms, as measured by scores on part three of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) during on time — or periods when symptoms were well-controlled with medication.

At the start of the trial, the average score was about 15 points for patients in both the lixisenatide and placebo groups. However, after a year on therapy, motor symptom severity was largely stable for patients on lixisenatide (average scores improved by 0.04 points), while it worsened by 3.04 points for patients on the placebo.

After completing the 12 months of treatment, all patients underwent a two-month washout period where they received no study drug. Following this period, MDS-UPDRS scores had worsened notably for patients in both groups, though average scores were still lower for patients who had received lixisenatide (17.7 vs. 20.6 points).

Other measures were generally comparable between the lixisenatide and placebo groups.

“For 30 years, we have been trying to understand how to slow the decline associated with Parkinson’s disease over time,” said Wassilios Meissner, MD, PhD, and Olivier Rascol, MD, PhD, who were co-principal investigators of the study. “In this context, the positive results of the LixiPark phase 2 trial showing less progression of motor symptoms of Parkinson’s disease over a year constitute a significant step forward in the future management of the disease.”

The researchers noted one serious side effect, a case of pancreatitis (pancreas inflammation), was deemed related to lixisenatide treatment.

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GI side effects more common with lixisenatide than with placebo

However, gastrointestinal side effects, such as nausea, vomiting, and reflux, were more common with lixisenatide than with a placebo. Due to these side effects, about a third of patients on lixisenatide were treated with a 10 microgram dose instead of the 20 micrograms planned.

All in all, the scientists concluded lixisenatide “modestly reduced motor disability progression in patients with early Parkinson’s disease as compared with placebo but had gastrointestinal side effects.”

“Larger and longer trials are needed to determine the effect and safety of this agent in the treatment of Parkinson’s disease,” the scientists added.

Notably, another GLP-1 receptor agonist called exenatide has previously shown similar effects in a Phase 2 Parkinson’s trial. Exenatide is currently being tested in Parkinson’s patients in a Phase 3 trial called Exenatide-PD3 (NCT04232969), with results expected later this year.

“This is the second phase 2 clinical trial indicating that this class of diabetes drugs is doing something interesting in Parkinson’s,” said Simon Scott, PhD, director of research at Cure Parkinson’s. “We congratulate the investigators who conducted this study, and we are truly grateful to the participants and their families for helping to advance the research into disease modifying therapies for Parkinson’s.”