A large phase III clinical trial has tested the diabetes drug exenatide (a GLP-1 receptor agonist) as a potential treatment for Parkinson’s disease. The trial aimed to determine whether the drug could slow down the disease’s progression or improve motor function. After nearly two years of follow-up, the results showed that exenatide was safe. Whether it offer a clinical benefit? Let’s find out in this article.
Parkinson’s disease is caused by the gradual loss of dopamine-producing neurons in the brain. Without dopamine, patients experience tremors, stiffness, slower movement, and eventually difficulties with balance and daily activities. Current medications like levodopa temporarily replace dopamine but do not slow the underlying progression of the disease.
Because of this gap, researchers have been searching for disease-modifying therapies—treatments that go beyond symptom management and actually change the course of the illness. Exenatide, originally developed for type 2 diabetes, attracted interest because it has shown potential neuroprotective effects in animal studies. Smaller, earlier clinical studies suggested that exenatide might improve Parkinson’s symptoms even after patients stopped taking the drug, raising hopes that it could be a breakthrough in slowing disease progression.
To test these early signals, researchers at several UK hospitals launched a phase III clinical trial of exenatide in people with Parkinson’s disease. The aim was to determine whether the drug could slow disease progression or improve motor symptoms over nearly two years. Here is how the study was designed and what the results revealed.
How was the study designed?
The study was conducted across six UK hospitals and enrolled almost 200 participants with mild to moderate Parkinson’s disease. Participants were randomly assigned to receive either weekly injections of extended-release exenatide (2 mg) or a placebo for 96 weeks, nearly two years. Neither the patients nor the clinicians knew who was receiving the drug or placebo, ensuring objectivity.
The main outcome of interest was the change in motor function after 96 weeks, assessed with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III in the “off” medication state (when patients were not taking their usual dopamine-replacement drugs). Researchers also used dopamine transporter imaging (DaT-SPECT) to see if the drug influenced dopamine activity in the brain.
What the trial found
Safety results
Exenatide was generally well tolerated over the 96 weeks. Serious adverse events were reported in 9% of patients in the exenatide group and 11% in the placebo group, suggesting no additional risks beyond what would normally be expected. This is important, because any long-term treatment for Parkinson’s needs to be safe and manageable for patients already coping with a chronic condition.
Motor outcomes
Despite its safety, exenatide did not provide the hoped-for benefit. On average, motor scores worsened by 5.7 points in the exenatide group and 4.5 points in the placebo group over 96 weeks. The adjusted difference between groups—0.92 points—was not statistically significant. In other words, the drug did not slow progression compared to placebo.
Brain scans (DaT-SPECT) also showed no meaningful differences in dopamine activity between the groups. Together, these findings indicate that exenatide did not affect either the symptoms or the underlying biology of Parkinson’s in this trial.
What the results mean
The findings are clear: exenatide, at least at the tested dose and duration, does not modify the course of Parkinson’s disease. This is a disappointing outcome, especially after smaller trials had suggested possible benefits. However, negative results are still valuable because they prevent false hope and help redirect research efforts to more promising approaches.
Importantly, the trial demonstrates that exenatide can be used safely for long periods in people with Parkinson’s disease. While this does not translate into clinical improvement, it provides reassurance for researchers exploring related drugs in the same class.
Placing the findings in context
Earlier phase II studies of exenatide had suggested modest improvements in motor symptoms, even when patients stopped taking the drug. These results generated significant excitement and justified the investment in a large phase III trial. By contrast, the current study did not replicate those outcomes, underlining why large, well-controlled trials are essential before a treatment can be considered effective.
It is also worth noting that Parkinson’s disease is complex and heterogeneous. What works for one subgroup of patients may not work for another, and measuring subtle disease-modifying effects remains challenging. The study’s outcome does not mean that GLP-1 receptor agonists as a class are ineffective, but it does show that exenatide in its current form is not the solution many had hoped for.
Where research goes next
The research community is not stopping with this result. Investigators are analyzing whether certain subgroups of patients—perhaps defined by age, genetic background, or disease stage—responded differently to exenatide. It is possible that effects were present in smaller groups but were not visible in the overall analysis.
At the same time, other GLP-1 receptor agonists, such as lixisenatide and liraglutide, are still in clinical trials. These drugs may have better penetration into the brain or stronger effects on inflammation and metabolism, two pathways thought to play a role in Parkinson’s progression. Researchers are also exploring whether combining GLP-1 drugs with other therapies could produce additive benefits.
Final takeaway
The Exenatide-PD3 phase III trial provides a definitive answer to an important question: Does exenatide slow Parkinson’s disease progression? The evidence says no. The drug is safe, but it does not improve motor outcomes or alter the underlying disease over nearly two years of treatment.
While disappointing, these results refine our understanding of where Parkinson’s research should head next. Not every promising idea will succeed, but each well-conducted trial brings the field closer to treatments that can truly modify the disease. The search continues, with other GLP-1 receptor agonists and novel approaches under investigation.
