GLP1 agonists
What is it: Diabetes medications under study for their potential neuroprotective effects in Parkinson’s.- ⬤ Minimal research: Very little scientific study exists, with no or very few peer-reviewed studies. Insufficient data for conclusions.
- ⬤⬤ Limited research: Few studies exist, mostly small trials or case reports. Findings are preliminary and lack strong validation.
- ⬤⬤⬤ Moderately researched: Multiple studies, including mid-sized trials, exist. Some findings are replicated, but more research is needed.
- ⬤⬤⬤⬤ Well-researched: Supported by substantial evidence, including at least one large trial or meta-analysis.
- ⬤⬤⬤⬤⬤ Extensively studied: Numerous large studies and meta-analyses exist. Findings are widely accepted with strong scientific consensus.
- ⬤ Extremely Difficult to Access: Rare, experimental, or highly specialized. Requires multiple referrals, long wait times, travel, and strict follow-up.
- ⬤⬤ Difficult to Access: Limited to select centers with moderate barriers. Requires referral, potential travel, and wait times of weeks to months.
- ⬤⬤⬤ Moderately Accessible: Available in larger hospitals or clinics. Requires a basic referral, with moderate wait times and some coordination.
- ⬤⬤⬤⬤ Easy to Access: Widely available in most clinics. Minimal referral, short wait times, and simple preparation or follow-up.
- ⬤⬤⬤⬤⬤ Trivial to Access: Easily found in pharmacies or clinics. No referral needed, minimal wait, and straightforward access.
- ⬤ Up to $100
- ⬤⬤ Up to $500
- ⬤⬤⬤ Up to $2000
- ⬤⬤⬤⬤ Up to $10,000
- ⬤⬤⬤⬤⬤ More than $10,000
To calculate the reported effectiveness for a patient view, the model first analyses whether it can be ascertained that the person writing the review has had direct experience of the treatment for themselves or a loved one. If so, it then uses sentiment analysis to rate their view from 1-5 on how effective this treatment was for them, with 1 being the least effective, and 5 the most effective.
24 Resources
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48 Research papers
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24 Expert views
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34 Patient views
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Figure out what GLP1 agonists means for you
Page contents
Basics: What you need to know
Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide, were originally developed for managing type 2 diabetes by enhancing the body’s insulin release and reducing blood sugar levels. In recent years, research suggests these agents may also benefit people with Parkinson’s disease by slowing disease progression and improving certain motor and cognitive symptoms.
History and development
- Origins in diabetes: GLP-1 receptor agonists came from studies of the hormone GLP-1, which helps regulate insulin production in type 2 diabetes.
- Discovery by Dr. Eng: Exenatide, a synthetic version derived from Gila monster saliva, was first identified by Dr. John Eng in the 1990s; it led to clinical use in diabetic care.
- Repurposed for PD: Observations of their neuroprotective effects in laboratory models pushed scientists to test GLP-1 receptor agonists in Parkinson’s disease, resulting in preliminary human trials.
- Early clinical trials: Small-scale studies indicated possible benefits for motor function, sparking broader interest and additional research on disease-modifying properties.
What is known
- Blood-brain barrier: GLP-1 receptor agonists can cross the blood-brain barrier, allowing them to act directly on brain cells, potentially stabilizing dopamine-producing neurons.
- Motor improvement: Some clinical trials with exenatide observed improvement in motor scores measured by standard Parkinson’s disease rating scales.
- Neuroprotective actions: Studies suggest reduced inflammation and protection against oxidative stress, both of which may help slow illness progression.
- Secondary benefits: Possible improvements in mood, cognitive function, and overall metabolic health—beyond basic diabetes control—have been reported.
What is not known
- Long-term effects: Definitive proof that these drugs truly modify Parkinson’s progression rather than merely offering symptomatic relief is still lacking.
- Optimal dosage: The best dosing and treatment duration for maximum neuroprotective benefit remain unclear.
- Mechanistic details: Exactly how GLP-1 receptor agonists protect or restore neuronal function has not been fully outlined.
- Broad applicability: Whether all individuals with Parkinson’s disease respond equally, or if certain subgroups benefit more significantly, is still under investigation.
- Neuroprotective action: May shield dopamine neurons from damage by reducing inflammation.
- Enhanced insulin signaling: Improves cellular energy use in the brain, potentially aiding neuronal survival.
- Blood-brain involvement: Crosses into the central nervous system for direct therapeutic impact.
- Anti-inflammatory role: Lowers harmful immune responses, which are linked to disease progression.
- Gastrointestinal issues: Nausea, vomiting, or diarrhea are commonly reported.
- Loss of appetite: Some individuals experience decreased hunger or unintentional weight loss.
- Hypoglycemia risk: Especially for those also taking other blood sugar-lowering medications.
- Possible pancreatitis: Though rare, inflammation of the pancreas has been reported.
- Uncertain durability: Some experts question whether benefits persist long term.
- Cost considerations: These drugs can be expensive, limiting widespread adoption.
- Regulatory status: Approval for Parkinson’s use is not yet standardized worldwide.
- Incomplete data: More large-scale trials are needed to confirm definitive effects.
Patient views
Experiences
- Patients appreciate potential neuroprotective effects of GLP-1 agonists.
- Weight loss benefits improve overall health and confidence.
- Some report reduced Parkinson's symptoms like rigidity and bradykinesia.
- Improved impulse control noted by some users.
Challenges
- Nausea and weight loss are common side effects.
- Heavy sweating and dizziness reported by some patients.
- Uncertainty about long-term effectiveness or progression slowing.
- High costs for self-pay treatments in some regions.
Tips
- Start with lower doses to manage side effects like nausea.
- Consult neurologists or endocrinologists before starting treatment.
- Consider compounding pharmacies for cost-effective options.
- Pair treatment with exercise and healthy diet for better outcomes.
To calculate the reported effectiveness for a patient view, the model first analyses whether it can be ascertained that the person writing the review has had direct experience of the treatment for themselves or a loved one. If so, it then uses sentiment analysis to rate their view from 1-5 on how effective this treatment was for them, with 1 being the least effective, and 5 the most effective.
Patient view
I'm on a GLP-1. I don't know if it's working re: delaying Parkinson's progression. It's certainly working super well for weight loss which in turn has made me sleep better and feel more confident/excited to go to the gym and both of those things are certainly related to quality of life with Parkinson's. The fact that the GLP1 could potentially be helping delay progression with Parkinson's in the long term is certainly an additional upside, but not anything I'm going to be able to confirm in the short-term or probably even in the long-term.
June 2024 • /r/Parkinsons
Patient view
Have read everything there is to read about GLP-1 drugs. Here is a little summary
Several phase 2 studies are positive for exenatide and one for lixisenatide. Liraglutide trial is negative.
Exposition for GLP1 was around 1 year, motor symptoms were stable or regressive, still ongoing two months after the end of the GLP1 exposition. When looking at the supplementary data, results were positive mostly for YOPD patients < 60 years old.
NLY01 trial (pegylated exenatide) was negative for the primary objective, but when looking at subgroups, again positive for < 60 YO patients.
I have myself started exenatide two months ago and not taking any dopamine medication. I am happy as it seems to work for me : less rigidity, less bradykinesia and my arm has started swinging again (it was not moving at all before). No adverse effect except some nausea the first two weeks.
June 2024 • /r/Parkinsons
Expert views
What they liked
- Experts appreciate GLP-1 agonists' potential to slow Parkinson's progression.
- Positive results in early trials showed motor symptom stabilization.
- Drugs like exenatide are already FDA-approved for diabetes, ensuring safety data.
- Convenient weekly dosing options improve patient compliance.
What they didn't like
- Phase 3 trials showed no significant benefit for Parkinson's symptoms.
- Side effects like nausea, weight loss, and GI issues concern experts.
- Difficulty in blinding trials due to visible side effects complicates research.
- Experts worry about overuse by non-diabetic Parkinson's patients.
What are they unsure about
- Experts are uncertain why early trial success wasn't replicated in later trials.
- Questions remain about the exact mechanism of action in Parkinson's.
- Difficulty in designing unbiased trials due to side effects raises doubts.
- Experts are unsure if benefits vary by Parkinson's stage or patient type.
24 expert views
Expert view
Dr. Simon Stott discussed the potential of GLP-1 agonists, like exenatide and lixisenatide, in treating Parkinson's disease. He highlighted that in a study, patients on exenatide showed initial improvement in symptoms and maintained this level for 48 weeks, unlike those on a placebo whose symptoms worsened. After stopping the drug, researchers observed the effects during a 'washout' period. Another study in France with lixisenatide, involving over 150 participants across 23 sites, also showed promising results, with a slowing of motor progression in patients.
November 2023 • Cure Parkinson’s Research Update Autumn 2023 – with Dr Simon Stott, Director of Research
Expert view
GLP1 agonists, originally approved for diabetes and obesity due to their ability to regulate blood sugar and promote weight loss, are now being explored for Parkinson's disease. Laboratory models suggest these drugs might have protective benefits for Parkinson's. Researchers have conducted initial trials using a GLP1 drug called exenatide, with some studies funded by the Michael J. Fox Foundation. This research is part of a broader effort to find new therapeutic options for Parkinson's.
November 2023 • Webinar: "A Year Like No Other in Parkinson's Research: 2023 in Review" November 2023
What and who it targets
Cognitive decline cases
May improve cognitive function.
Patients with mild motor symptoms
Effective for initial symptom control.
Early-stage patients
Potential to slow disease progression.
Relevant research
How much evidence on this?
Numerous studies show GLP-1 agonists' neuroprotective effects in Parkinson's.
Research focusing on
- Improves motor and cognitive symptoms; reduces inflammation and oxidative stress.
What needs more research?
Long-term effects and disease-modifying potential unclear.
- ⬤ Minimal research: Very little scientific study exists, with no or very few peer-reviewed studies. Insufficient data for conclusions.
- ⬤⬤ Limited research: Few studies exist, mostly small trials or case reports. Findings are preliminary and lack strong validation.
- ⬤⬤⬤ Moderately researched: Multiple studies, including mid-sized trials, exist. Some findings are replicated, but more research is needed.
- ⬤⬤⬤⬤ Well-researched: Supported by substantial evidence, including at least one large trial or meta-analysis.
- ⬤⬤⬤⬤⬤ Extensively studied: Numerous large studies and meta-analyses exist. Findings are widely accepted with strong scientific consensus.
Research
This paper explored whether GLP-1 receptor agonist therapy could protect brain cells in rodent models of Parkinson's disease. Researchers analyzed data from eleven studies, focusing on two main outcomes: brain chemical activity related to dopamine and motor symptoms.
The study found that GLP-1 receptor agonists significantly improved dopamine-related brain activity and motor symptoms in rodent models of Parkinson's disease. These improvements were statistically significant, suggesting potential benefits of this therapy.
For someone living with or caring for someone with Parkinson's, this research suggests that GLP-1 receptor agonists might offer a new way to protect brain cells and improve movement. However, these findings are based on animal studies, so more research is needed to confirm benefits in humans.
This paper is a systematic review, which is a high-quality type of study that combines data from multiple sources. It was published in a reputable journal, but the findings are limited to pre-clinical rodent models and need further validation in human trials.
February 2022 • Clinical parkinsonism & related disorders
Research
This paper systematically reviewed 289 studies to explore the neuroprotective role of GLP-1 (Glucagon-like peptide 1) and its mechanisms. It analyzed both clinical and preclinical studies, focusing on neurodegenerative diseases like Parkinson's and Alzheimer's, as well as neurovascular complications.
The review found that GLP-1 and its agonists can partially or fully reverse neurotoxic effects, improve neuron survival, and reduce inflammation. Mechanisms include boosting neuron growth factors, reducing cell death, and strengthening the blood-brain barrier.
For someone with Parkinson's, this research suggests that GLP-1 agonists might help protect brain cells and reduce disease progression. However, more clinical trials are needed to confirm these benefits in humans.
This systematic review is reliable as it includes a large number of studies and was published in a reputable journal. However, the findings are mostly based on preclinical studies, so clinical relevance is still uncertain.
April 2019 • Brain injury
Accessibility
- ⬤ Extremely Difficult to Access: Rare, experimental, or highly specialized. Requires multiple referrals, long wait times, travel, and strict follow-up.
- ⬤⬤ Difficult to Access: Limited to select centers with moderate barriers. Requires referral, potential travel, and wait times of weeks to months.
- ⬤⬤⬤ Moderately Accessible: Available in larger hospitals or clinics. Requires a basic referral, with moderate wait times and some coordination.
- ⬤⬤⬤⬤ Easy to Access: Widely available in most clinics. Minimal referral, short wait times, and simple preparation or follow-up.
- ⬤⬤⬤⬤⬤ Trivial to Access: Easily found in pharmacies or clinics. No referral needed, minimal wait, and straightforward access.
- ⬤ Up to $100
- ⬤⬤ Up to $500
- ⬤⬤⬤ Up to $2000
- ⬤⬤⬤⬤ Up to $10,000
- ⬤⬤⬤⬤⬤ More than $10,000
Method to access
- Requires consultation with a neurologist or specialist.
- Often accessed through clinical trials or off-label prescriptions.
- Not available for at-home use.
Cost
- Annual costs for GLP-1 agonists range from $12,000 to $13,500 in the US.
- Prices may vary globally, but high costs are typical due to limited insurance coverage.
Insurance cover
- Insurance coverage is limited and often excludes off-label use for Parkinson's Disease.
- Coverage is more common for FDA-approved uses like Type 2 diabetes.
Locations
- Cleveland Clinic: Conducted trials on GLP-1 agonists for Parkinson's.
- UK research hospitals: Participated in exenatide trials.
- Specialized clinics in Turkey, Spain, and Switzerland: Known for innovative Parkinson's treatments.
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