Parkinson's: a diabetes drug could delay the progression of motor symptoms

A type 2 diabetes drug slowed the progression of Parkinson's disease symptoms, according to a French study testing lixisenatide effects on 156 patients.

Slowing the progression of motor symptoms

The randomised, double-blind LixiPark3 study, recently published in the New England Journal of Medicine, was based on the follow-up of 156 patients with early-stage Parkinson's disease. They were diagnosed less than three years ago, were already taking medication to treat their symptoms, and were not yet showing a marked decline in their motor skills.

They were randomly assigned to receive, in addition to their usual treatment, either lixisenatide®, a GLP-1 receptor agonist used to treat diabetes, or a placebo.

After 12 months, those who received lixisenatide® showed virtually no further deterioration in the motor skills associated with Parkinson's disease, while those who received a placebo saw their symptoms worsen.

This difference between the two groups was statistically significant, indicating that lixisenatide® may delay the progression of motor symptoms in people with Parkinson's disease. These findings were consistent at the end of the 12-month treatment period as well as two months after stopping treatment.

The link between diabetes and Parkinson's disease

Research has already shown a link between Parkinson's disease and type 2 diabetes. People with type 2 diabetes have a higher risk of developing Parkinson's disease, and when they do, their symptoms progress more rapidly than in people without diabetes.

According to Dr Daniel Truon (Director of the Truong Neuroscience Institute at Memorial Care Orange Coast Medical Center) for Medical News Today1, this link between the two conditions is based on several similarities. In particular, he cites insulin resistance and glucose dysregulation, inflammation and oxidative stress, mitochondrial dysfunction, α-Synuclein pathology, as well as shared genetic risk factors.

Dr Truong also points out that chronic low-grade inflammation and oxidative stress are common features of diabetes and Parkinson's disease. Research suggests that inflammatory processes in the brain may play a role in the progression of Parkinson's disease, and there is evidence linking inflammation to insulin resistance in diabetes. Studies have also shown that mitochondrial dysfunction contributes to insulin resistance and beta cell problems in diabetes, while also being a key aspect of the degeneration of dopaminergic neurons in Parkinson's disease.

According to Dr Truong, emerging evidence suggests that α-Synuclein pathology may be present in a variety of tissues, including pancreatic beta cells in diabetes. This paves the way for further research into the role of alpha-synuclein aggregation in diabetes-related complications and its potential link to Parkinson's disease.

Dr Truong concludes by saying that overall, these findings suggest a convergence of pathophysiological mechanisms between diabetes and Parkinson's disease. Consequently, drugs that target these mechanisms, such as GLP-1 receptor agonists, could offer advantages in the treatment of both conditions.

Further tests required

Despite these promising results, further research and probably a phase 3 study are still needed before long-term treatments for Parkinson's disease with GLP-1 receptor agonists can be proposed. This includes dose optimisation, combined therapies, safety and tolerability, as well as effects on non-motor symptoms. In particular, half of the study participants who received lixisenatide® complained of nausea.

At present, no GLP-1R agonist, including lixisenatide®, is approved for the treatment of Parkinson's disease.

  1. Ozempic-like drug may help slow the progression of Parkinson's symptoms, 9 avril 2024, Finn Cohen for Medical News Today 
  2. Lixisenatide: diabetes drug may slow progress of Parkinson’s, 8 avril 2024, Parkinson Erope.
  3. Trial of Lixisenatide in Early Parkinson’s Disease, 3 avril 2024, New England Journal of Medicine