In April 2024, the New England Journal of Medicine published results of a Phase 2 clinical trial of a diabetes drug lixisenatide, testing whether the medication could slow progression of Parkinson’s disease (PD). This trial, like others testing the class of drugs known as GLP-1 receptor agonists, shows mixed results—some promising, some needing further investigation. 

The findings have sparked a lot of conversation, even appearing in The New York Times. They have also sparked a lot of questions, which we hope to help answer. 

What was the trial testing? 

Phase 2 clinical trials like this one test the safety of a treatment, extending to more people and longer timeframes than Phase 1 trials. However, while the trials are primarily testing safety, Phase 2 studies often include measurements to get a first look at whether a treatment is doing what investigators hope it will do. 

In this case, the trial tested a Type 2 diabetes drug called lixisenatide, an injection which is in the same class of drugs (GLP-1 receptor agonists) as popular medications Ozempic and Wegovy. While assembling safety data, the study also collected measures of the medication’s impact on motor symptoms. 

What did the trial show? 

The primary measure the trial used to show potential benefit (MDS-UPDRS part III, which measures motor symptoms) was “positive” in that it showed that people treated with lixisenatide held largely steady in their test score, while the control group taking a placebo treatment continued to progress. While the difference between those treated with lixisenatide and those on placebo was modest, this positive signal is encouraging for researchers aiming to slow or even stop the progression of Parkinson’s. 

However, secondary measures, including what patients reported to researchers about their symptoms, did not confirm the same slowing of progression seen with the motor measures. There could be multiple reasons for this, including that the treatment might need more than the year allotted in the trial to show meaningful slowing from a patient perspective.   

When the researchers looked at participants two months after stopping treatment (after a so-called “wash-out” period), the difference between those who took lixisenatide and those who took placebo remained (implying the potential for a lasting effect). Still, more consistent and longer-term measures are needed to draw meaningful conclusions. 

Also, more than half of people taking the treatment reported significant gastrointestinal issues (e.g., nausea and vomiting), with more than a third needing a reduced dose of lixisenatide because of it. It is possible that such side effects could have “unblinded” participants and the study investigators who normally should not know who is taking drug and who is on placebo. Such unblinding can potentially (and unintentionally) bias how people are measured on symptom scales. 

Who was in the trial? 

156 people participated in the trial, each within 3 years of their Parkinson’s diagnosis. To be selected to participate, people needed to be taking stable dopamine medication but not yet experiencing some of the later stage complications of those medicines, like fluctuations in symptoms or dyskinesia. 

The trial followed participants (who were randomly either assigned lixisenatide or a placebo) for a year. 

What needs further study? 

The lixisenatide study only accounts for a small fraction of the research being done on GLP-1 receptor agonists in Parkinson’s. For example, there is a large, multicenter Phase 3 clinical trial of a similar treatment (exenatide). The top-line results of that trial are due to be reported in the second half of 2024. 

This work builds on earlier findings, including a Phase 2 exenatide trial that showed similar possibilities for motor effect. However other trials within the same class of drugs have reported no meaningful effect, including studies on therapies like NLY01 and PT320. 

Even beyond effect, there is lots still to learn about using GLP-1 receptor agonists for Parkinson’s. While the drugs have proved beneficial and safe in diabetes, researchers have not yet fully investigated this in Parkinson’s. For example, weight loss (often a desired effect of these treatments) may not be desirable for people with PD. We also don’t know yet if this drug is safe for chronic use in people with Parkinson’s,or how it interacts with current PD treatments. 

Should people with Parkinson’s adjust their treatment regimens? 

Lixisenatide is still considered experimental for Parkinson’s and more research is required before it can potentially become part of a well-informed treatment regimen. There are currently no GLP-1 receptor agonists, including lixisenatide, that are approved for use in Parkinson’s, though studies continue to investigate the potential.