- In a study of people with early-stage Parkinson’s disease, a GLP-1 receptor agonist showed promising results in reducing impaired motor skills associated with Parkinson’s.
- Lixisenatid — commonly used to treat diabetes — was given to half of the cohort for a year, and their motor skills deterioration showed almost no progression compared with the people who received a placebo.
- Experts say the results of the study are promising but warrant further long-term research with larger groups.
Scientists have found that a drug commonly used to treat type 2 diabetes can help reduce the development of motor skills deterioration in people with early-stage Parkinson’s, according to the findings of a new study published in The New England Journal of Medicine.
The study, which was randomized, double-blind, and placebo-controlled, followed 156 participants in France whose diagnosis of Parkinson’s had been within the last three years, were on a stable regime of medication to treat symptoms, and who did not yet have marked decline in motor skills. The participants were either given lixisenatide, a GLP-1 receptor agonist that is used to treat diabetes or a placebo.
After 12 months, the 78 people who had been given lixisenatide showed virtually no further deterioration of motor skills that is commonly seen with Parkinson’s disease, while those who were given a placebo saw a worsening of those symptoms. Nearly half of the group who took lixisenatide reported nausea and 13% experienced vomiting.
Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, told Medical News Today that while GLP-1 receptors are a relatively new field, the results of the study were promising.
“It is a fascinating study that is proof of concept that this class of medications may have some protective effect and be of advantage to someday treat Parkinson’s. It will be interesting to see if the results hold true for other newer GLP-1 agents like Ozempic/Wegovy and Zepbound,” Gabbay said.
Parkinson’s is a disorder characterized by significant neurological decline that can manifest in tremors, motor control problems, and dementia. There is no known cause, but it is associated with a lack of dopamine in the brain. It is the
Daniel Truong, MD, neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, told MNT that links between Parkinson’s and diabetes hinge on several common threads between the disorders:
- insulin resistance and glucose dysregulation
- inflammation and oxidative stress
- dysfunction of mitochondria
- alpha-synuclein pathology
- shared genetic risk factors
“There is ongoing research exploring the potential links between diabetes and Parkinson’s disease. Several studies have suggested that individuals with diabetes may have a higher risk of developing Parkinson’s disease, and vice versa,” Truong said.
“Chronic low-grade inflammation and oxidative stress are common features of both 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.”
— Daniel Truong, MD
“Studies have shown that mitochondrial dysfunction contributes to insulin resistance and beta-cell dysfunction in diabetes, while mitochondrial impairment is also a key feature of dopaminergic neuron degeneration in Parkinson’s disease,” Truong explained.
“Emerging evidence suggests that alpha-synuclein pathology may also be present in peripheral tissues, including pancreatic beta cells in individuals with diabetes. Further research could explore the role of alpha-synuclein aggregation in diabetes-related complications and its potential link to Parkinson’s disease,” he added.
GLP-1 (glucagon-like peptide-1) receptor agonists are part of a treatment regimen for people with type 2 diabetes. They can help reproduce or enhance the effects of a naturally occurring gut hormone that assists in the control of blood sugar levels, and they can also reduce appetite by working on brain hunger centers; this is one of the reasons drugs like Ozempic and Wegovy have been associated with weight loss.
Truong said that a drug like lixisenatide has neuroprotective effects, which would clearly provide some assistance for people with a neurological disorder like Parkinson’s. But he also pointed out how common traits in both diabetes and Parkinson’s can provide some insight into GLP-1 receptor agonists as a way to reduce Parkinson’s symptoms.
“There is emerging evidence suggesting shared pathophysiological mechanisms between diabetes and Parkinson’s disease. For example, insulin resistance and impaired glucose metabolism have been implicated in both conditions. Therefore, drugs that target these mechanisms, such as GLP-1 RAs, might have beneficial effects in both diseases.”
— Daniel Truong, MD
“In some studies, the prevalence of Parkinson’s disease was lower among patients with diabetes who were treated with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 inhibitors, which increase GLP-1 levels, than among patients who received other diabetes medications,” Truong said.
Truong said that the study’s limitations warrant further research to establish several aspects of long-term treatment of Parkinson’s with GLP-1 receptor agonists: dose optimization, combination therapies, safety and tolerability, and effects on the non-motor symptoms.
“Parkinson’s disease is associated with a wide range of non-motor symptoms, including cognitive impairment, autonomic dysfunction, and psychiatric symptoms. Future studies should investigate whether lixisenatide has beneficial effects on non-motor symptoms in addition to motor symptoms,” he said.
“Although the study suggested a potential neuroprotective effect of lixisenatide, the underlying mechanisms are not fully understood. Further research is needed to elucidate the specific neuroprotective mechanisms of lixisenatide in Parkinson’s disease, including its effects on inflammation, oxidative stress, mitochondrial function, and alpha-synuclein pathology,” he explained.
