Diabetes Drug May Reduce Parkinson’s Risk

A type of drug used to treat diabetes may reduce the risk of developing Parkinson’s disease.

A type of drug used to treat diabetes may reduce the risk of developing Parkinson’s disease, according to a new study published in PLOS Medicine.

The research, led by the London School of Hygiene & Tropical Medicine, found that diabetes patients taking glitazone antidiabetes drugs (either rosiglitazone or pioglitazone) had a 28% lower incidence of Parkinson’s disease than people taking other treatments for diabetes who had never taken glitazones.

Glitazones are a class of drug that activate the peroxisome proliferation-activated gamma (PPARγ) receptor, which is found inside cells in many different body organs. PPARγ activation by glitazones leads to reduced insulin resistance, which has been useful for treating people with diabetes, but the receptor has many other functions that have not been studied as thoroughly in humans.

Although the potential effect of glitazones on Parkinson’s disease had previously been demonstrated in rodents and in vitro, the authors believe this is the first study to show the relationship between glitazone use and incidence of Parkinson’s disease in humans.

This image is a drawing of a man with Parkinson's disease.
The results showed a 28% reduction in incidence of Parkinson’s disease among people taking glitazones compared with those taking other antidiabetic treatments. Adjustments for risk factors associated with Parkinson’s disease (including smoking and head injury) had no impact on the findings. Image is for illustrative purposes only. Image credit: Sir William Richard Gowers.

The study, which was funded by The Michael J Fox Foundation for Parkinson’s Research, looked at more than 160,000 diabetes patients in the UK. Researchers used electronic health records from the UK Clinical Practice Research Datalink to match 44,597 glitazone users with 120,373 people using other antidiabetic drugs. Glitazone users were matched by age, sex, GP practice, and diabetes treatment stage with up to five users of other diabetic treatments.

Patients were followed up from 1999 (when glitazones were introduced to treat diabetes) until 2013, to determine how many were diagnosed with Parkinson’s disease during that period.

The results showed a 28% reduction in incidence of Parkinson’s disease among people taking glitazones compared with those taking other antidiabetic treatments. Adjustments for risk factors associated with Parkinson’s disease (including smoking and head injury) had no impact on the findings.

The results suggest that the reduced risk of Parkinson’s disease was only associated with current treatment with glitazones, and that there is little or no longer lasting benefit if people have taken the drug in the past before stopping or switching to another medication.

Senior author Dr Ian Douglas from the London School of Hygiene & Tropical Medicine said: “We often hear about negative side effects associated with medications, but sometimes there can also be unintended beneficial effects.

“Our findings provide unique evidence that we hope will drive further investigation into potential drug treatments for Parkinson’s disease. It’s thought that around one in 500 people are affected by Parkinson’s, and to date no effective treatments have been found to directly tackle the neurodegenerative aspect of the disease.”

Dr Ruth Brauer, who worked on the study while at the London School of Hygiene & Tropical Medicine, said: “Our results suggest that treatments which activate the PPARγ receptor in the same way as glitazones could be promising targets in future drug research. Although our study only looked at people with diabetes, we believe it’s likely that the protective effect of glitazones may also be seen in people without diabetes.”

The authors note that their study only included patients with diabetes who had not been diagnosed with Parkinson’s disease when they started taking glitazones, and therefore they cannot establish whether taking the drug slows or prevents the progression of the disease. They also highlight that glitazones have been associated with some serious side effects.

About this Parkinson’s disease research

The study was carried out in collaboration with researchers at UCL and Imperial College London.

Funding: This work was supported by The Michael J Fox Foundation for Parkinson’s Research.

Source: Jenny Orton – London School of Hygiene & Tropical Medicine
Image Credit: The image is credited to Sir William Richard Gowers
Original Research: Full open access research for “Glitazone treatment and incidence of Parkinson’s disease among people with diabetes: a retrospective cohort study” by Ruth Brauer, Krishnan Bhaskaran, Nishi Chaturvedi, David T Dexter, Liam Smeeth, and Ian Douglas in PLOS Medicine. Published online July 21 2015 doi:10.1371/journal.pmed.1001854


Abstract

Glitazone treatment and incidence of Parkinson’s disease among people with diabetes: a retrospective cohort study

Background

Recent in vitro and animal experiments suggest that peroxisome proliferation-activated receptor gamma (PPARɣ) agonist medications, such as antidiabetic glitazone (GTZ) drugs, are neuroprotective in models of Parkinson’s disease (PD). These findings have not been tested in humans. We hypothesized that individuals prescribed GTZ drugs would have a lower incidence of PD compared to individuals prescribed other treatments for diabetes.

Methods and Findings

Using primary care data from the United Kingdom Clinical Practice Research Datalink (CPRD), we conducted a retrospective cohort study in which individuals with diabetes who were newly prescribed GTZ (GTZ-exposed group) were matched by age, sex, practice, and diabetes treatment stage with up to five individuals prescribed other diabetes treatments (other antidiabetic drug-exposed group). Patients were followed up from 1999 until the first recording of a PD diagnosis, end of observation in the database, or end of the study (1 August 2013). An incidence rate ratio (IRR) was calculated using conditional Poisson regression, adjusted for possible confounders. 44,597 GTZ exposed individuals were matched to 120,373 other antidiabetic users. 175 GTZ-exposed individuals were diagnosed with PD compared to 517 individuals in the other antidiabetic drug-exposed group. The incidence rate (IR) of PD in the GTZ-exposed group was 6.4 per 10,000 patient years compared with 8.8 per 10,000 patient years in those prescribed other antidiabetic treatments (IRR 0.72, 95% confidence interval [CI] 0.60–0.87). Adjustments for potential confounding variables, including smoking, other medications, head injury, and disease severity, had no material impact (fully adjusted IRR 0.75, 0.59–0.94). The risk was reduced in those with current GTZ prescriptions (current GTZ-exposed IRR 0.59, 0.46–0.77) but not reduced among those with past prescriptions (past GTZ-exposed IRR 0.85, 0.65–1.10). Our study only included patients with diabetes who did not have a PD diagnosis when they were first prescribed GTZ, and thus, it cannot establish whether GTZ use prevents or slows the progression of PD.

Conclusions

In patients with diabetes, a current prescription for GTZ is associated with a reduction in incidence of PD. This suggests PPAR gamma pathways may be a fruitful drug target in PD.

“Glitazone treatment and incidence of Parkinson’s disease among people with diabetes: a retrospective cohort study” by Ruth Brauer, Krishnan Bhaskaran, Nishi Chaturvedi, David T Dexter, Liam Smeeth, and Ian Douglas in PLOS Medicine. Published online July 21 2015 doi:10.1371/journal.pmed.1001854

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