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Common Diabetes Medication as Treatment for Parkinson’s Disease

Feb 16, 2021
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Arjay Mendoza, PharmD Candidate, University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences

Findings show Parkinson’s disease risk is reduced in patients with type 2 diabetes mellitus (T2DM) after treatment with exenatide. 

People with Parkinson’s disease in the United Kingdom are currently being recruited for a placebo-controlled Phase 3 clinical trial called Exenatide-PD3 (NCT04232969) after research suggested that they could be treated with this common diabetes medication. 

 

The new findings are published in the academic journal Brain, which shows that Parkinson’s disease’s risk is reduced among people with Type 2 Diabetes Mellitus (T2DM) after they are given the medication. 

Exenatide (Byetta® and Bydureon®) is a GLP-1 agonist often prescribed to treat patients with T2DM. It is proven to be safe and effective against diabetes. It helps lower blood glucose levels by mimicking incretin hormones that are naturally produced by the body. It also stimulates the release of insulin and suppresses glucagon secretion only when blood glucose levels are elevated.  

Now, pre-clinical studies have shown robust and reproducible evidence that this medication has beneficial “disease-modifying” effects when given to animals with Parkinson’s disease symptoms. Besides that, laboratory work has also suggested that GLP-1 agonists might have neuroprotective properties that could be used as a potential treatment for other degenerative disorders.  

Patients with T2DM have a higher risk of developing Parkinson’s disease at some point in their lives than those without diabetes. However, commonly prescribed anti-diabetic medications such as GLP-1 agonists and DPP-4 inhibitors appeared to have the opposite effect on this relationship. The researchers found out that patients who are taking either a GLP-1 agonist (e.g., exenatide) or DPP-4 inhibitors were 36% to 60% less likely to be diagnosed with Parkinson’s disease after a few years (average follow-up time of over 3.3 years), compared to patients who are taking other classes of anti-diabetic medications.  

Hence, a team of researchers at the University College of London (UCL) is leading the Phase 3 clinical trial, including an estimated 200 patients. It aims to assess and compare Parkinson’s disease’s risk in a larger population of patients with T2DM. The patients were being treated with different types of anti-diabetic medications, including GLP-1 agonists. The research team is funded by The Cure Parkinson’s Trust, which examined patient records from over 100,000 patients with T2DM from The Health Improvement Network Database. 

Patients were selected if they were diagnosed with T2DM and received at least two anti-diabetic medications between 2006 and 2019. Afterward, statistical analyses were conducted to compare Parkinson’s disease’s risk between patients treated with different types of diabetes medications such as glitazones, DPP-4 inhibitors, GLP-1 agonists, and other oral anti-diabetic drugs. Patients taking insulin were analyzed separately. 

Of the 100,288 patients with T2DM, 329 participants (0.3%) were diagnosed with Parkinson’s, which averaged a median followup of 3.3 years. Afterward, the researchers compared 21,175 patients treated with glitazones, 36,897 patients taking DDP4 inhibitors, and 10,684 patients taking GLP-1 agonists, versus 38,393 patients who received some other combination of oral anti-diabetic medications. 

Compared to patients who are taking other anti-diabetic medications, the incidence of Parkinson’s disease was lower in those taking glitazones (eight per 10,000 person-years), DPP-4 inhibitors (five per 10,000 person-years), and GLP-1 agonists (four per 10,000 person-years (PY). Indeed, DPP-4 inhibitors and GLP-1 agonists (such as exenatide) were linked to a lower risk of developing Parkinson’s disease in patients with T2DM. 

A separate analysis was performed for those patients receiving insulin, but it yielded similar results compared to patients receiving other anti-diabetic medications. However, this sub-set is underpowered due to a small number of participants taking insulin. 

Professor Foltynie, one of the study authors, confirmed a link between T2DM and Parkinson’s disease, stating that while most people with diabetes will not go on to develop Parkinson’s, the study provided evidence to support that GLP-1 agonists such as exenatide may help prevent or treat Parkinson’s disease. However, further research is needed before making any clinical recommendation regarding its use.  

Practice Pearls: 

  • The use of GLP-1 agonists or DPP-4 inhibitors is associated with a lower rate (36% to 60% less likely) of Parkinson’s disease when compared to patients who are taking other oral anti-diabetic medications. 
  • Pre-clinical studies of exenatide show that it has beneficial disease-modifying effects when given to animals with Parkinsons disease symptoms. 
  • Exenatide (Byetta® and Bydureon®) is a GLP-1 agonist, which helps lower blood glucose levels by mimicking the activity of incretin hormones that are naturally produced by the body. 

 

Athauda, Dilan et al. “Exenatide once weekly versus placebo in Parkinson’s disease: a randomized, double-blind, placebo-controlled trial.” Lancet (London, England) vol. 390,10103 (2017): 1664-1675. doi:10.1016/S0140-6736(17)31585-4 

Foltynie, Thomas et al. “Diabetes medications and risk of Parkinson’s disease: a cohort study of patients with diabetes.” Brain, vol. 143, 10 (2020): 3067-3076. doi:10.1093/brain/awaa262 

 

Arjay Mendoza, PharmD Candidate, University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences