GLP-1 and Parkinson's Disease: Research, Benefits and Risks

GLP-1 receptor agonists, medications licensed for type 2 diabetes and obesity, are being investigated for potential neuroprotective effects in Parkinson's disease. Whilst these drugs—including exenatide, liraglutide, and semaglutide—are not approved for neurological conditions, emerging research suggests they may influence brain health through mechanisms beyond glucose control. GLP-1 receptors exist in brain regions affected by Parkinson's, prompting clinical trials to explore whether these agents might slow disease progression or improve motor symptoms. Currently, their use in Parkinson's remains experimental, with no NHS or NICE recommendation outside of clinical trials. This article examines the scientific rationale, current evidence, and important safety considerations surrounding GLP-1 receptor agonists and Parkinson's disease.

What Are GLP-1 Receptor Agonists?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily licensed for the treatment of type 2 diabetes mellitus and, more recently, obesity. These medicines work by mimicking the action of the naturally occurring hormone GLP-1, which is released from the intestine in response to food intake. The primary mechanism involves stimulating insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning they only promote insulin release when blood glucose levels are elevated.

In the UK, commonly prescribed GLP-1 receptor agonists include exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), semaglutide (Ozempic, Wegovy, Rybelsus), and lixisenatide (Lyxumia). These medications are administered either as subcutaneous injections (daily or weekly, depending on the formulation) or, in the case of semaglutide, as an oral tablet. Beyond their glucose-lowering effects, GLP-1 receptor agonists slow gastric emptying, reduce appetite, and promote weight loss—effects that have made them valuable in managing obesity.

The MHRA has approved these agents specifically for metabolic conditions. NICE guidance (NG28) recommends GLP-1 receptor agonists in type 2 diabetes only for specific patients, typically when other treatments have proven insufficient and when certain BMI thresholds are met. For obesity management, NICE technology appraisals specify strict eligibility criteria for liraglutide (Saxenda) and semaglutide (Wegovy). However, emerging research has identified that GLP-1 receptors are not confined to the pancreas and gastrointestinal tract; they are also present in the brain, including regions affected by neurodegenerative diseases. This discovery has sparked considerable scientific interest in whether GLP-1 receptor agonists might offer neuroprotective benefits beyond their established metabolic effects, particularly in conditions such as Parkinson's disease.

The Link Between GLP-1 and Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra, a region of the brain crucial for movement control. This neuronal loss leads to the cardinal motor symptoms of Parkinson's: tremor, rigidity, bradykinesia (slowness of movement), and postural instability. The exact cause of neuronal death in Parkinson's remains incompletely understood, but contributing factors include oxidative stress, mitochondrial dysfunction, neuroinflammation, and abnormal protein aggregation (particularly alpha-synuclein).

The potential connection between GLP-1 receptor agonists and Parkinson's disease stems from the presence of GLP-1 receptors in the brain, including the substantia nigra, hippocampus, and cortex. Preclinical studies in animal models have suggested that some GLP-1 analogues may cross the blood-brain barrier, though the extent of this penetration in humans remains uncertain. Laboratory studies have demonstrated potential neuroprotective effects, including reducing oxidative stress, decreasing inflammation, promoting neuronal survival, and enhancing mitochondrial function—all processes that are impaired in Parkinson's disease.

Furthermore, epidemiological studies have observed that people with type 2 diabetes generally have an increased risk of developing Parkinson's disease, though the relationship is complex with multiple confounding factors. Some research suggests that chronic hyperglycaemia and insulin resistance may influence neurodegeneration, whilst other studies have noted that certain diabetes medications might modify Parkinson's risk. It is important to emphasise that there is no official link establishing GLP-1 receptor agonists as a treatment for Parkinson's disease; rather, the biological plausibility and promising preclinical data have prompted clinical investigation into whether these drugs might slow disease progression or alleviate symptoms in people living with Parkinson's.

Mounjaro®

Average 22.5% body weight loss

Mounjaro® is the most innovative GLP-1 medication proven to dramatically curb appetite, hunger, and cravings to help professional men achieve substantial weight loss.

Start Here

Wegovy®

Average 16.9% body weight loss

Wegovy® is a weekly injectable GLP-1 medication with proven effectiveness in reducing appetite, hunger, and cravings to help busy professionals lose significant weight.

Start Here

Find out if you’re eligible

Current Research on GLP-1 Treatments for Parkinson's

Several clinical trials have explored the potential of GLP-1 receptor agonists in Parkinson's disease, with exenatide being the most extensively studied agent to date. A landmark phase 2 randomised controlled trial published in The Lancet in 2017 investigated exenatide in patients with moderate Parkinson's disease. Participants receiving once-weekly exenatide injections for 48 weeks showed modest improvements in motor scores compared to placebo, and these benefits persisted for 12 weeks after treatment cessation. Whilst these findings were encouraging, the study was relatively small and designed primarily to assess safety and feasibility rather than definitive efficacy.

More recently, a randomised controlled trial of lixisenatide in early Parkinson's disease (the LIXIPARK study) was published in the New England Journal of Medicine (2024). This study demonstrated a significant benefit on motor function (MDS-UPDRS part III in the OFF state) compared to placebo, though with notable gastrointestinal side effects. The researchers concluded that while promising, these findings require replication and longer follow-up to determine clinical significance.

Studies with liraglutide have shown mixed results, with some suggesting potential benefits alongside modest motor effects, though robust evidence for cognitive improvements is currently lacking. These trials collectively indicate that whilst GLP-1 receptor agonists appear safe in Parkinson's populations, the magnitude of clinical benefit remains uncertain.

It is crucial to recognise that all current research is investigational. GLP-1 receptor agonists are not licensed or recommended for Parkinson's disease treatment in the UK or elsewhere. The mechanisms underlying any potential benefit—whether through direct neuroprotection, metabolic improvement, anti-inflammatory effects, or other pathways—remain under investigation. Larger, longer-duration trials with robust outcome measures are needed to determine whether these medications can meaningfully alter the course of Parkinson's disease or improve quality of life for patients.

Potential Benefits and Risks of GLP-1 Therapy in Parkinson's

The theoretical benefits of GLP-1 receptor agonists in Parkinson's disease are grounded in their neuroprotective properties observed in laboratory and animal studies. These include:

• Neuroprotection: Reducing oxidative stress and inflammation that contribute to dopaminergic neuron death

• Mitochondrial support: Enhancing cellular energy production, which is often impaired in Parkinson's

• Protein clearance: Potentially improving the removal of toxic protein aggregates like alpha-synuclein

• Metabolic benefits: Addressing insulin resistance and glucose dysregulation, which may influence neurodegeneration

However, these potential advantages must be weighed against known adverse effects of GLP-1 receptor agonists. The most common side effects are gastrointestinal, including nausea, vomiting, diarrhoea, and constipation—symptoms that can be particularly problematic in Parkinson's patients who often already experience autonomic dysfunction and gastroparesis. Importantly, GLP-1 receptor agonists typically cause weight loss, which may be undesirable or even harmful in Parkinson's patients at risk of malnutrition or who are experiencing unintentional weight loss.

Other significant considerations include:

• Injection site reactions (for subcutaneous formulations)

• Hypoglycaemia risk (particularly if used alongside other glucose-lowering medications)

• Pancreatitis (rare but serious)

• Gallbladder disease (including gallstones and cholecystitis)

• Dehydration leading to acute kidney injury (particularly with severe gastrointestinal side effects)

• Diabetic retinopathy complications (particularly noted with semaglutide in diabetes patients)

• Potential thyroid effects (medullary thyroid carcinoma risk in animal studies, though human relevance remains unclear)

A Parkinson's-specific concern is that GLP-1 receptor agonists delay gastric emptying, which may further impair levodopa absorption and potentially worsen motor fluctuations or 'OFF' periods in patients on this medication.

Patients with Parkinson's disease should not use GLP-1 receptor agonists outside of clinical trials or specific medical supervision for diabetes or obesity. Any decision to prescribe these medications must involve careful discussion between the patient, their neurologist, and other relevant specialists, with consideration of individual circumstances, comorbidities, and the current evidence base.

NHS Guidance and Clinical Trials in the UK

Currently, NICE guidance (NG71) for Parkinson's disease does not recommend GLP-1 receptor agonists for treating this condition. These medications remain licensed exclusively for type 2 diabetes mellitus and obesity. Their use in Parkinson's is considered off-label and experimental. While off-label prescribing is legally permitted under specialist supervision with informed consent, it is not routinely commissioned for Parkinson's disease in the NHS.

Several UK-based clinical trials are investigating this potential therapeutic avenue. The Exenatide-PD3 trial, a large phase 3 study, is evaluating whether exenatide can slow Parkinson's disease progression over an extended period. This multicentre trial aims to provide more definitive evidence regarding efficacy and safety. Additionally, researchers at various UK institutions are exploring the mechanisms by which GLP-1 receptor agonists might influence neurodegeneration, using advanced imaging and biomarker studies.

For patients interested in participating in research, the following resources may be helpful:

• NIHR Be Part of Research (bepartofresearch.nihr.ac.uk) – search for Parkinson's and GLP-1 trials

• Parkinson's UK (www.parkinsons.org.uk) – information on current research and trial opportunities

When to contact your GP or specialist:

• If you have Parkinson's disease and diabetes, and wish to discuss whether a GLP-1 receptor agonist is appropriate for your diabetes management

• If you experience new or worsening symptoms whilst taking any medication

• If you are interested in clinical trial participation—your neurologist can advise on suitable studies

Seek urgent medical attention if you experience:

• Severe, persistent abdominal pain (possible pancreatitis)

• Persistent vomiting or inability to keep fluids down (risk of dehydration)

• Signs of dehydration (extreme thirst, dark urine, dizziness)

• Allergic reaction (rash, swelling, difficulty breathing)

Patients should never start, stop, or modify medications without medical supervision. If you experience any suspected side effects from medication, report them through the MHRA Yellow Card scheme (www.mhra.gov.uk/yellowcard). Whilst the research into GLP-1 receptor agonists and Parkinson's disease is promising, it remains in relatively early stages, and robust evidence from large-scale trials is needed before these drugs can be recommended for neuroprotection or symptom management in Parkinson's disease.

Frequently Asked Questions