The connection between diabetes and Parkinson’s

We’ve all heard about the dangers of sugar and eating too much of it. But actually, sugar is not all bad. Our bodies need a form of sugar called glucose to function properly. And it is this sugar that fuels our brains, the most energy demanding organ in the body.

The food and drink we consume throughout the day provides the source of glucose. The body has carefully controlled ways to make sure this fuel is available to cells to power their important functions.

Food is digested and important components are absorbed from the gut into the bloodstream. Signals are sent from the gut to an organ called the pancreas, which releases a hormone called insulin. Insulin helps the body use and store glucose, removing it from the bloodstream.

It is when this carefully regulated system is not functioning as it should that problems begin to occur. In diabetes the body doesn't produce enough or any of the hormone insulin or the body can’t use the hormone effectively. This means that the glucose in the blood cannot be used by cells and also doesn’t get stored away. If left unmanaged, levels of sugar in the blood can become dangerously high and levels of fuel inside cells dangerously low. Diabetes drugs work to restore the balance.

So beyond glucose being vital to power brain cells, why is this relevant to Parkinson’s? 

Sugar and Parkinson’s

The symptoms of Parkinson’s occur partly due to the death of specific brain cells that produce an important brain chemical called dopamine. Dopamine is vital in controlling muscle movement but can also have a knock on effect to other non-movement related symptoms.

Researchers are working to unpick what is causing brain cells to die in Parkinson's with the hope to find a way to slow or stop the condition. Something no current treatment can do.

In Parkinson’s it has been shown that energy production within brain cells is not as efficient as it should be. As well as the structures in our cells that produce energy, called mitochondria, not  working as well as they should in Parkinson’s, it is also thought that glucose is not as available to cells, just like in diabetes. When this happens, the cells do not have enough energy to function and can become stressed. This can lead to the cells dying and not producing the vital dopamine needed for the brain to function normally.

Diabetes and Parkinson’s

This might start to explain why there is growing evidence that people with type 2 diabetes may have an increased risk of developing Parkinson’s. And people living with diabetes and Parkinson’s possibly see their Parkinson’s progress faster.

It has also been observed in a large proportion of people with Parkinson's, who don't have diabetes, that their body is not as responsive to insulin as expected. There is ongoing research looking into understanding more about the role of insulin and glucose in Parkinson’s.

Alongside the quest for more answers about the root causes of Parkinson’s, there are already trials exploring whether a particular group of existing diabetes drugs could be beneficial for the condition. The hope is that these medications may help to better fuel brain cells with glucose, so that they can carry out their important functions.

Repurposing diabetes drugs for Parkinson’s 

There are a specific type of diabetes drugs that work to lower blood sugar levels by increasing the release of insulin from the pancreas. They work by targeting glucagon-like peptide-1 (GLP-1) receptors in the pancreas, which causes the release of insulin and results in increased uptake of glucose by cells.

They are being investigated for Parkinson’s because GLP-1 receptors are also found in the brain, and lab-based experiments have suggested that activating these receptors can boost the function of dopamine connections, have anti-inflammatory properties, improve energy production, and switch on cell survival signals.

Promising results in the lab have led to trials of these specific type 2 diabetes drugs in people with Parkinson’s to see if they can slow or stop the progression of the condition.

Let’s summarise the three main type 2 diabetes drugs that have provided clinical insights for Parkinson’s to date:

Liraglutide 

• Clinical trial of 63 participants where people were given either once-daily injections of liraglutide or placebo injections for 52 weeks. 
• Results were presented back in 2022.
• Improvements were observed in non-motor symptoms and quality of life. 
  However, there was no clear difference in motor symptoms between those on liraglutide and those on the placebo.

Lixisenatide 

• Results shared April 2024 from a clinical trial of lixisenatide (LixiPark). 
  156 people with Parkinson’s took part, who were less than 3 years into their diagnosis.
• 75 people received daily injections of lixisenatide, and 75 people an inactive (placebo) injection, over 12 months.
• Movement symptoms in people with Parkinson’s receiving lixisenatide treatment did not deteriorate over a 12 month period, compared to those receiving a placebo where there was a slight worsening.  
• But the study didn’t show any changes to their quality of life, or measurements of non-motor symptoms.

Read more about the 2024 lixisenatide results in our research news story. 

Exenatide 

• In 2013, an exploratory trial of exenatide in 45 people with Parkinson’s reported promising results - potentially slowing the progression of movement and cognitive symptoms. 
• A follow-on placebo controlled trial of exenatide began in 2014, involving 60 people with Parkinson’s over 60 weeks. Half the participants injected themselves with exenatide once a week for 48 weeks. The other half (the placebo group) did exactly the same but were receiving a dummy version of the drug.
• Those who received exenatide had a slight and statistically significant improvement when their movement was assessed while off their regular Parkinson’s medication. Crucially, this difference between the two groups was still there when they were re-assessed 12 weeks after treatment had been stopped.
• All participants underwent brain scans (called DaTscans) at the start and end of the trial. There were subtle signs in the scans that exenatide may be slowing the loss of brain cells, but again, the differences were too small to be conclusive and further research is required.
• One of the most puzzling things about the results from the 2014 exenatide trial is that exenatide was not recorded to improve quality of life or non-motor symptoms. 
• There is an ongoing phase 3 trial of exenatide. Results are expected at the end of 2024.

What’s next for diabetes drugs and Parkinson’s?

While the clinical research to date is encouraging, there is not enough evidence to say conclusively that these types of diabetes drugs protect brain cells. But the phase 3 trial of exenatide has the potential to provide insights into some of the unanswered questions. The Parkinson's community urgently needs new treatments so they, and we, eagerly await the results from this ongoing phase 3 trial, expected later this year.

Note: It is essential that drugs are properly tested to ensure that they are safe and beneficial for people with Parkinson’s and do not interact with any other medication that they are on. We would not recommend people to go out and take these drugs, unless they have been recommended by a medical professional for other reasons.