Long-term Pioglitazone Use May Reduce Risk of Parkinson Disease in Patients With Diabetes

Pioglitazone use among patients with diabetes was associated with a significantly reduced risk of Parkinson disease (PD), according to study findings published in Journal of Clinical Neuroscience.

PD is the fastest growing neurological condition worldwide, threatening the physical and mental health of middle-aged and elderly people. Prior research has shown that PD diagnosis is associated with significant economic burden, in which nonacute institutional care, inpatient hospitalization, and outpatient care are the largest drivers of cost among differing coverage plans.

Although the specific pathogenesis and etiology of PD are not fully clarified, diabetes has been indicated to potentially share similar pathophysiology with the neurodegenerative condition and to be a risk factor for development.

“Thus, antihyperglycemic agents may have beneficial effects on PD. Pioglitazone is a peroxisome proliferator activated receptor (PPAR) agonist that can improve hyperglycemia and insulin resistance… and the treatment effect of pioglitazone as a neuroprotective agent for PD has been confirmed in nonhuman primate and rodent models,” said the study authors. “However, whether pioglitazone can minimize the risk of PD in patients with diabetes remains controversial.”

Researchers conducted a systematic review and meta-analysis to evaluate the effect of pioglitazone on PD in patients with diabetes, as well as the association between dose-duration-day (DDD) of the drug and risk of PD.

Studies within the PubMed, Embase, and Web of Science databases from inception to July 22, 2021, were examined during the review, with the Newcastle-Ottawa scale (NOS) used to evaluate the quality of the eligible studies. The studies were divided into at least 3 dose groups based on the DDD of pioglitazone.

After eliminating duplicate studies, 540 studies were obtained, of which only 3 retrospective cohort studies met the inclusion criteria and were relevant for the meta-analysis.

The studies were conducted in Taiwan and the United Kingdom with 131,410 participants, and the publication years ranged from 2015 to 2020. Across the overall patient cohort, the mean age and follow-up duration were 57.91 to 63.60 and 5 to 6.13 years, respectively. The NOS score of the eligible studies was 7-8, suggesting that the included studies had relatively high quality.

Results of the meta-analysis showed there was a significant reduction in the risk of PD among pioglitazone users vs nonusers with diabetes (risk ratio [RR], 0.87; 95% CI, 0.62-0.99; P = .039).

After accounting for dose response, no significant difference in PD risk was noted in patients with diabetes taking 438 DDDs of pioglitazone or lower compared with nonusers. When the DDD of pioglitazone was 438, a 15% lower risk of PD was observed (RR, 0.85; 95% CI, 0.72-1.00; P = .05), and when the DDD of pioglitazone was greater than 438, the risk of PD in patients with diabetes was significantly decreased (P < .05) and showed an approximate linear correlation trend.

The sole use of retrospective cohort studies was noted to be a potential limitation of the study findings.

“The studies included in this study did not report the reaction of PD drug treatment, whether the PD exists in the family history, gene mutation, and other information, and it was uncertain whether these features have been included in the correction factors, which should be further explored,” they added.

The researchers concluded that more high-quality studies may be warranted to confirm the treatment effect of pioglitazone on PD prevention.

Reference

Chen L, Tao Y, Li J, Kang M. Pioglitazone use is associated with reduced risk of Parkinson’s disease in patients with diabetes: a systematic review and meta-analysis. J Clin Neurosci. 2022;106:154-158. doi:10.1016/j.jocn.2022.10.023