A class of drugs used to treat diabetes may be associated with protection against Parkinson's disease (PD), according to research published this week in PLOS Medicine. The study, conducted by Dr. Ruth Brauer, of the London School of Hygiene & Tropical Medicine, found a lower incidence of PD among people using a glitazone drug (either rosiglitazone or pioglitazone) to treat diabetes when compared to people who had used different treatments for diabetes.
The cohort study was conducted using data from the UK Clinical Practice Research Datalink, and compared individuals with diabetes who were exposed to glitazones (44,597 total) with up to five individuals with diabetes who never used glitazones (120,373 in total), matched on age, sex, primary care practice, and diabetes treatment stage. The researchers analyzed the records of these patients from 1999, when glitazones were introduced to treat diabetes, until 2013. During that time, individuals who had used glitazones to treat diabetes were 28% less likely to be diagnosed with PD than individuals with diabetes who never used glitazones. Adjusting for known predictors of PD such as smoking and head injury did not alter this association. When the researchers considered past and current glitazone users separately, they found that the decreased incidence in PD was only observed in individuals currently using a glitazone (a 41% decrease in PD incidence), not those who had previously used glitazone but stopped or switched to another medication, indicating little to no persisting benefit of glitazone use.
These findings are consistent with animal and in vitro studies which suggested that glitazones and other drugs that target peroxisome proliferation-activated receptor gamma (PPARγ) may have neuroprotective effects. It is important to note that these results may not apply to people without diabetes and do not indicate whether glitazones can slow PD progression. Further, it is possible that unknown patient characteristics associated with glitazone use might also be linked to PD, contributing to the appearance of a direct causal connection. In addition, glitazones have been associated with serious side effects.
However, the authors are hopeful that these findings may pave the way towards other treatments that target the same pathway: "Our findings indicate that interventions based on the same mechanisms as PPARγ agonist activity may be fruitful targets for future research in PD."
Funding: We received a research grant from the Michael J. Fox Foundation for Parkinson's Research. ID is funded by a Medical Research Council methodology research fellowship, KB is funded by a National Institute for Health Research postdoctoral fellowship, and LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science grant number 098504/Z/12/Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: LS has received research funding from GSK and ID has consulted for, and holds stock in, GSK.
Citation: Brauer R, Bhaskaran K, Chaturvedi N, Dexter DT, Smeeth L, Douglas I (2015) Glitazone Treatment and Incidence of Parkinson's Disease among People with Diabetes: A Retrospective Cohort Study. PLoS Med 12(7): e1001854. doi:10.1371/journal.pmed.1001854
Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom
Institute of Cardiovascular Sciences, University College London, London, United Kingdom
Centre for Neuroinflammation & Neurodegeneration, Division of Brain Sciences, Faculty of Medicine, Imperial College, London, United Kingdom
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