Diabetes and Parkinson’s: Can GLP-1 Drugs Slow PD Progression?

Is the future of Parkinson’s neuroprotection hidden in a diabetes drug?

In this episode of Live Parkinson’s – Live an Exceptional Life, we pull back the curtain on the "Metabolic Mind." We explore the link between Type 2 Diabetes and Parkinson’s Disease, and why the research world is focused on GLP-1 receptor agonists (the class of drugs including Ozempic and Wegovy) as potential "fire extinguishers" for brain inflammation.

In this episode, you’ll discover:

• The Biological Bridge: Why people with Type 2 Diabetes have a 32% to 40% higher risk of developing Parkinson’s.

• The Data Duel: A deep dive into the landmark Lixisenatide study (NEJM, 2024), which showed zero motor progression over a year, versus the recent Exenatide Phase 3 results (The Lancet, 2025).

• Shared Mechanisms: How insulin resistance, mitochondrial "power failure," and chronic neuroinflammation drive both diseases.

• The Move Toward Precision Medicine: Insights from the September 2025 Frontiers in Aging Neuroscience study on how managing your metabolic health is a fundamental strategy for protecting your brain.

Try This Today:  Call your doctor and establish a Metabolic Baseline. Know and understand your HbA1C and Fasting Insulin levels to start playing "offense" against neurodegeneration through targeted nutrition and exercise.

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 WATCH & SUBSCRIBE: Head to my YouTube channel for daily tips and our new series on Daily Living with Parkinson's.

Disclaimer: This podcast is for educational purposes and is not intended to treat or diagnose Parkinson's Disease. Always consult your do

Transcript

GLP-1s Beyond Weight Loss

Three Shared Villains Explained

LixiPark Trial Findings

Exenatide Phase 3 Reality Check

Rethinking PD As Multisystem

From Science To Daily Actions

Calls To Learn, Support, Engage

SPEAKER_00 0:10

Hello, and welcome to Live Parkinson's Live an Exceptional Life. I'm your host, Chris Kustenbotter, and I've been living an exceptional life with Parkinson's for the past 15 years. The mission of this podcast is to help as many people as possible living with Parkinson's to lead a great quality of life. What if the secret to slowing down Parkinson's progression isn't hidden in a dopamine bottle, but in how our cells process energy? Well, today we're diving into the medical bridge that is fundamentally changing how we look at neurodegeneration. You've probably all seen the headlines or heard the ads for Ozepic and Mogovi, and may even know people who are using these medications, the GLP1 drugs, which have been taking the world by storm for weight loss. But in the research world, these are being studied as potential fire extinguishers for the brain. So in today's episode, we're going to be breaking down the latest clinical research and answering the big question: can managing your metabolism save your brain? So let's give you a roadmap of what we'll be covering and how you can use this information in your Parkinson's journey now. And we'll start it off with the biological bridge and look at the shared villains and look at brain insulin resistance, mitochondrial failure, and neuroinflammation, all in simple terms that we can all understand, because most of us are not neuroscientists. Then we'll look at the data dual between two of the latest studies, one from the New England Journal of Medicine in 2024 and the Lancet study from 2025. And then it's on to what you can do with the information and discuss, try this today, managing your metabolic baseline. Then we'll tie it all together and send you on your way. So if you're ready, let's dive in. First, let's start with what GLP1s do or what they are. Because most of us have heard of GLP1s in the news, but might not be familiar with what they actually are. Well, to understand the potential of GLP1s, which stand for glucagon-like heptide 1 receptor agonists, and that's a mouthful, it's best to think of them not as just diabetes drugs, but as a new way to manage how our brain cells process energy and protect themselves from damage. So what are GLP1s and what do they currently do? Well, GLP1 is a natural hormone in the body that's going to help regulate blood sugar by transulin and controlling your appetite. Now, these medications we call GLP1s like Ozempic and Wagovi, and older versions like a xenotide were originally created to treat type 2 diabetes and help with weight loss. They work by mimicking the natural hormone, essentially, quote, tickling the receptors in the body and the brain to improve metabolic function. So now that we know what GLPs are and what they do, let's look at the shared mechanisms and why we're looking at the connection between diabetes and Parkinson's. So to answer this, we first have to look at the why. Why are we even talking about diabetes drugs for a movement disorder? And that's a pretty fair question, right? Well, according to the Parkinson's Foundation Science News, there's a massive overlap between type 2 diabetes and Parkinson's disease. In fact, research indicates that people with type 2 diabetes have a 32 to 40% higher risk of developing Parkinson's. And that's significant if you ask me. So let's look at the three shared villains in our story that disrupt both diabetes and Parkinson's. Our first villain is insulin resistance in the brain. So just like your muscles can stop responding to insulin, the neurons or brain cells can too. And when that happens, they can't get the energy they need to function, leading to what researchers call brain energy failure. Now, in my case, I constantly have brain failure. At least it feels that way sometimes. Villain two is mitochondrial power failure. So think of the mitochondria as the power plants of your cells. So if you remember that from high school biology, then give yourself a gold star. Yep, they're the powerhouse of the cell. And in both diabetes and Parkinson's, these power plants start flickering out and creating oxidative stress that damages the neurons. And then our third villain is chronic inflammation. High blood sugar and insulin resistance create a quote fire, if you will, of inflammation that spreads through the brain, accelerating the loss of dopamine-producing neurons. So, what these villains do has shown researchers that Parkinson's is not just a dopamine deficiency, but it's a complex multi-system disorder involving protein folding and energy conversion. Okay, now let's switch gears and talk data because this is really where I hope hits the hard truth. In April 2024, there was a study published in the New England Journal of Medicine titled The LixiPark Trial, a trial of Lexysenatide in early Parkinson's disease. And this was a study that took a popular diabetes medication, a GLP1 receptor, agonist, and tested it on people with Parkinson's. So who was involved in this study? The study focused on 156 people in early stages of Parkinson's, meaning they were diagnosed for less than three years and who were already stable on dopamine medications. And they were split into two equal groups. One group gave themselves a daily injection of lixycenotide and the other received a placebo. Alright, so what were the results? Well, the big discovery after one year were remarkable. The group taking the actual drug, lixycenotide, showed virtually zero progression in their motor symptoms like tremors and stiffness. Specifically, their motor scores improved slightly by 0.04 points or four hundredths of a point, while the group on the placebo followed the typical path of the disease with the symptoms worsening by 3.04 points. Then the researchers had the participants do what they call a washout period, meaning they had all the participants stop taking their shots for two months. The results? Even after the drug was out of their system, the people who had taken lixy cenitide still had significantly better motor scores than those who hadn't. So this suggests that the drug actually might be doing more than masking symptoms. It may actually be protecting the brain's power plants, the mitochondria, and acting as a fire extinguisher for neuroinflammation. Now, while this is incredibly optimistic, there are a few hurdles to keep in mind. The first is side effects. Nearly half, 46% of the people taking the drug experienced nausea, and 13% experienced vomiting. So in terms of clinical meeting, while the three-point difference in results was statistically positive, it fell short of the 3.5 mark that doctors usually considered clinically meaningful for a person's daily life. Finally, in terms of availability, lixysenatide was actually removed from the market by its manufacturer for business reasons in 2023, and it's currently only exists in combinations with insulin that are not suitable for people with Parkinson's. Now, this result from 2024 does sound promising. However, and I always want to give you the straight data-driven truth, the momentum shifted in early 2025. The journal The Lancet published a study titled, and it's a long one, Xenotide Once a Week versus placebo as a potential disease modifying treatment for people with Parkinson's disease in the UK. Phase three multi-center, double-blind, parallel group randomized placebo-controlled trial. And again, it was published in the Lancet on February 4th, 2025. And this research was the largest and longest trial to date investigating whether the diabetes drug Axenotide could slow down the progression of Parkinson's. The study setup included researchers recruiting 194 people with moderate severity Parkinson's across six hospitals in the UK. And for 96 weeks, nearly two full years, half of the participants gave themselves a weekly injection of a xenoti, while the other half used a virtually identical placebo injection. Now, because it was a double-blind study, neither the participants nor the doctors knew who was getting the real medication until the very end of the study. The results? Despite high hopes fueled by the earlier smaller trials, this phase three trial found that a xenotide had no positive impact on the movement symptoms or brain imaging of people with Parkinson's. When researchers checked off medication scores, which measured the underlying severity of the disease, the group taking the drug actually worsened slightly more, 5.7 points, than those on the placebo at 4.5 points. So what this means for you and those of us with Parkinson's is that the door is closed on a xenotide. Experts suggest these results effectively close the door on using a xenotide specifically for Parkinson's. Second, this study contrasts sharply with the 2024 New England Journal of Medicine study on lixysenotide, which showed a small benefit. So this tells us that the different drugs in the GLP1 class interact with the brain in different ways. Researchers are now looking to see if specific subgroups, such as those with prediabetes, might still benefit from these types of drugs. But of course, more work and research is going to be needed. Now, adding to this study in the Lancet, another landmark study was published in September 18th, 2025, and Frontiers in Aging Neuroscience titled Understanding Parkinson's Disease, Current Trends and Multifaceted Complications. Now, this comprehensive review led by Samir Chihari and colleagues argues that Parkinson's is no longer just a movement disorder caused by dopamine deficiency. It's rather a multifactoral multisystem disorder that requires a move toward precision medicine. The study highlights that Parkinson's is the fastest growing neurological condition in the world. The number of people living with Parkinson's more than doubled between 1990 and 2016, and is projected to double again to 12 million by 2040. Now, this growth is not driven by aging, but by environmental exposure and industrial chemicals. A major focus of this 2025 review is the overlap between Parkinson's and other metabolic conditions, specifically type 2 diabetes. Now, the researchers noted that insulin resistance in the brain can actually drive the loss of neurons by starving them of the energy they need. Chronic inflammation acts like the fire in the brain, damaging the substantia nigra, and mitochondrial power failure occurs when the energy producing parts of our cells flicker out, creating oxidative stress. The study emphasizes that for many, PDs is a metabolic neurological hybrid, meaning managing your blood sugar and your metabolic health is a fundamental strategy for protecting your brain. Hmm. These sound like the three villains that we talked about earlier. Insulin resistance in the brain, mitochondrial dysfunction, and chronic inflammation. The review also sheds some light on the faceted complications that often precede motor symptoms by years. In terms of mental health, up to 60% of patients experience depression and anxiety. And then cognitive decline is another big one. Nearly 80% of those in the advanced stages may develop dementia, often linked to brain inflammation. And then gut health. The study supports the body first theory, suggesting that PD may start in the gut and is linked to gut dysbiosis, which means that there's an imbalance of your gut bacteria. It's often a reduction in the good bacteria and an increase in the harmful bacteria. And then they're going to travel to the brain via the vagus nerve, causing the inflammation. Now the researchers are incredibly optimistic about the tools arriving in 2026 and beyond. They highlighted artificial intelligence or AI and wearables that provide 24-7 biological fingerprint of symptoms, allowing your neurologist to fine-tune your medications with near perfection. They also point to high-tech breakthroughs like stem cell transplants to replace lost neurons, and CRISPR, C-R-I-S-P-R-CAS9 Gene Editing to Fix Genetic Mutations. Now you can learn more about this in one of my latest podcasts titled 2026 Parkinson's Breakthroughs, Stopping Progression with LRRK2, Stem Cells, and the New Biological Marker Revolution. So, what this means for all of us living with Parkinson's is that the era of the one size fits all treatment is ending. The study concludes that future care must be personalized, targeting a person's specific gene and metabolic profile. All right, that brings us to the end of all the science talk. And my goal with every episode is for you to leave every episode with some type of tool or strategy that you can use in your daily life. So one of the things you can do is ask your neurologist or your primary care doctor for a metabolic baseline, specifically your HBA1C and fasting insulin. Now, your doctor typically does this when they request blood work for you. And you would want to know this as well, even if you aren't a diabetic, pre-diabetic levels of blood sugar can trigger the brain inflammation we discussed. Now I want to state this clearly. And again, these are common tests that they typically run when you go for blood work for physicals or just your typical follow-up. So they're going to know how to properly manage your test results. And one of the this is one of the ways that they can help you manage your blood sugar levels in your daily life. That's through eating a good, healthy diet that's rich in fruits and vegetables, whole grains, and lean protein and healthy fats. So ask your doctor to recommend a diet for your specific needs. And you can also ask to go see a certified dietitian or nutritionist as well. Also be sure to include consistent, and that's the key word here, aerobic exercise. By combining both your diet and your exercise, you're helping to create a neuroprotective environment for your brain cells. So you can start your own metabolic movement habit. After the largest meal of the day, take a 15-minute brisk walk. Research shows that light aerobic exercise shortly after eating is highly effective in helping your body and your brain process glucose more effectively, which is a simple but powerful natural way to boost your insulin sensitivity. Alright. The story of GLP1s and Parkinson's is still being written, but the momentum has shifted. We are no longer playing defense. We are playing offense by targeting the very energy systems that keep our brain alive. So remember to help yourself by eating a good diet that doesn't contain a lot of high sugar foods or ultra-processed foods, and be sure to get consistent aerobic exercise. Now, if you found today's episode helpful, please visit LibParkinsons.com and subscribe to the free monthly newsletter, which delivers the latest breakthroughs, news, and educational opportunities to your inbox. And if you want to support my mission of helping people live an exceptional quality of life and help me create more resources, please click the support the show link in the description or visit my Kofi.com slash Lib Parkinsons page. Every little bit helps me reach more families. Finally, visit my YouTube channel and join the community. See the recent 30-day tips for living a great quality of life with Parkinsons. And then I'm just launching a new series titled Exceptional Life, 60 Days of Action, where I show you in my daily life how I use the four pillars exercise, nutrition, optimism, and social interaction to lead a great quality of life living with Parkinson's. So keep moving, stay optimistic, and remember the rules of Parkinson's are being rewritten, and you're part of the story. So go live your best life with Parkinson's, and I hope to see you soon. Thanks.