Could drugs like Ozempic help people with Parkinson’s disease? 

The Glucagon-like peptide-1 (GLP-1) agonist lixisenatide and its potential role in treating PD.

GLP-1 agonists are molecules that are approved for use to treat type 2 diabetes (you may be familiar with brand names like Ozempic and Weygovy). They act by mimicking human gut hormones or incretins to stimulate the release of insulin. Receptors for GLP-1 are also found in the brain and there has been a growing body of research showing that these molecules can have neuroprotective effects. One paper suggested that these neuroprotective effects may occur by blocking the activation of the immune cells of the brain which can be responsible for a damaging inflammatory response. You can read more about the connection between inflammation and PD here

GLP-1 agonists have been shown to improve various features of disease in animal models of PD which led to them being tested in clinical trials. In a small clinical trial in 2018, the GLP-1 agonist exenatide showed a moderate improvement in motor scores in PD patients. A more recent study investigated NLY01, a longer-acting form of exenatide. Results did not show an improvement in Parkinson’s disease motor or non-motor features compared with placebo. Liraglutide was also tested in a small clinical trial, but results have not yet been published. 

The latest news: A clinical trial of the GLP-1 agonist lixisenatide is the most recent to be completed and results were published this week in the New England Journal of Medicine and reported widely, including in the New York Times (APDA’s Scientific Advisory Board Chairman, Dr. David Standaert, is quoted in the article.) The study followed 156 people with PD within the first three years of diagnosis who were randomly assigned to either receiving the drug or placebo. At 12 months, motor scores in the placebo group had worsened, but not in the group receiving lixisenatide. Nausea was a very common symptom (46%) of those receiving lixisenatide.  

A larger trial will need to be conducted in order to confirm these results, but if a GLP-1 inhibitor is found to be useful in Parkinson’s disease, this would be extremely welcome news. Getting FDA approval for a brand-new drug is a massive undertaking. It is a simpler process to expand the indication of an existing medication as compared to gaining approval for a new medication. This is because an approved medication is a known quantity, with a well-established side effect profile, so there is less safety testing that needs to be done, and the process by which the drug is approved for the second purpose is typically shorter than when it is initially approved. This process is called repurposing a medication

APDA will closely monitor the research progress on lixisenatide and other GLP-1 agonists, as more data is collected on their use in PD. 

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