Certain Diabetes Medications Linked to Lower Parkinson’s Risk, Study Suggests

Certain types of anti-diabetic medications may lower the risk of Parkinson’s disease in people with type 2 diabetes, a population-based study suggests.

In particular, the risk of Parkinson’s was found to be 36–60% lower in diabetic patients who were being treated with GLP-1 agonists or DPP4 inhibitors compared with other oral medications.

These findings support the rationale behind a Phase 3 trial called Exenatide-PD3 (NCT04232969), which is exploring the therapeutic potential of exenatide (brand names Byetta and Bydureon) — a GLP-1 agonist often prescribed to treat type 2 diabetes — in patients with Parkinson’s. The trial, which will include an estimated 200 patients, is being led by a team of investigators at the University College of London.

The study, “Diabetes medications and risk of Parkinson’s disease: a cohort study of patients with diabetes,” was published in the journal Brain.

Several studies have reported that patients with type 2 diabetes have a higher risk of developing Parkinson’s at some point in their lives.

Preclinical studies have also suggested that GLP-1 agonists might have neuroprotective properties that could be useful in treating Parkinson’s. These agonists are anti-diabetic medications that help lower blood sugar levels by mimicking the activity of incretin hormones that are naturally produced by the body.

Following these findings, several clinical trials have been launched to explore the potential of repurposing these medications to treat Parkinson’s. Data from a Phase 2 trial (NCT01971242) evaluating exenatide in 60 individuals with Parkinson’s indicated that, when added to regular antiparkinsonian medication, exenatide might have positive effects on patients’ motor function.

With support from The Cure Parkinson’s Trust and the Barcapel Foundation, the current study was aimed at assessing and compare the Parkinson’s risk in a large population of patients with type 2 diabetes who were being treated with different types of anti-diabetic medications, including GLP-1 agonists.

Patients were identified and selected using The Health Improvement Network, a large database that contains anonymized electronic medical records collected from primary care clinics across the U.K. All patients who were diagnosed with diabetes and received at least two prescriptions for anti-diabetic medications between 2006 and 2019 were included in the analyses.

Statistical analyses were used to compare Parkinson’s risk between patients being treated with glitazones, DPP4 inhibitors, and GLP-1 agonists and those receiving other oral anti-diabetic medications. Patients using insulin were analyzed separately.

Of the 100,288 patients with type 2 diabetes identified, 329 (0.3%) were diagnosed with Parkinson’s at some point during follow-up, which lasted a median of 3.33 years.

Researchers compared 21,175 patients who were being treated with glitazones, of whom 36,897 were receiving DPP4 inhibitors, and 10,684 were being treated with GLP-1 agonists. A sub-set of 38,393 patients were being treated with other oral blood sugar-lowering agents.

Compared with patients receiving other anti-diabetic medications (10 per 10,000 person-years), the incidence of Parkinson’s was lower in those receiving glitazones (eight per 10,000 person-years), DPP4 inhibitors (five per 10,000 person-years), and GLP-1 agonists (four per 10,000 person-years).

For reference, person-years is a measure that takes into account the number of people participating in a study and the amount of time they were followed. So, 10,000 person-years pertains to data gathered by following 10,000 people for one year.

No evidence was found suggesting that the use of glitazones could be linked to a lower risk of Parkinson’s. However, the use of DPP4 inhibitors and GLP-1 agonists was linked to a 36–60% lower risk of Parkinson’s.

A separate analysis performed in patients using insulin in combination with these medications yielded similar results, despite being underpowered due to the small number of participants included.

“The use of DPP4 inhibitors and/or GLP-1 receptor agonists is associated with a lower rate of Parkinson’s disease compared to the use of other oral antidiabetic drugs. Our study provides unique evidence to support further investigation of DPP4 inhibitor and GLP-1 receptor agonist use in Parkinson’s disease,” the researchers wrote.