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.