Decreased risk of Parkinson’s disease in diabetic patients with thiazolidinediones therapy: An exploratory meta-analysis

Autoři: Yueli Zhu aff001;  Jiali Pu aff001;  Yanxing Chen aff001;  Baorong Zhang aff001
Působiště autorů: Department of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224236



It has been found that thiazolidinediones (TZDs) may play a protective role in animal models of Parkinson’s disease (PD), while the results remain controversial whether TZDs protect against Parkinson’s disease in humans. The purpose of this meta-analysis is to explore the association between TZDs use and the incidence of PD in diabetic patients.


A systematic online search was conducted to find studies published up to 31 December 2018. In our exploratory meta-analysis, studies comparing incidence of PD between TZD-treated and non-TZD-treated groups of diabetic patients were included. Data analysis was performed using a random or fixed effects model and expressed as odds ratios (OR) with 95% confidence interval (95% CI). We used the Cochrane Collaboration’s Review Manager 5.3 software to analyze data.


In total, 5 retrospective observational cohort studies were identified which met the inclusion criteria. The pooled odds ratio (OR) was 0.70 [95% CI, 0.51 to 0.96; p = 0.03] in a random-effects model, indicating a 30% lower risk of developing PD in diabetic patients treated with TZDs compared with non-TZD-treated patients.


In this exploratory meta-analysis, we found that TZDs use was associated with reduced risk of PD in diabetic patients. However, this meta-analysis was not registered online although we followed a protocol designed for it. Further prospective observational studies with larger sample size and more strict inclusion criteria including controlling for diabetes complication severity index, hypoglycemic drugs combination, sex ratio, and comorbidity are needed to guide whether RCTs are warranted. And RCTs can better determine whether TZDs use could lower incidence of PD in diabetic patients.

Klíčová slova:

Animal models – Cohort studies – Diabetes mellitus – Ethnicities – Metaanalysis – Parkinson disease – Publication ethics – Randomized controlled trials


1. Kalia LV, Lang AE. Parkinson's disease. The Lancet. 2015; 386: 896–912.

2. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson's disease: risk factors and prevention. The Lancet Neurol. 2016; 15: 1257–1272. doi: 10.1016/S1474-4422(16)30230-7 27751556

3. Shah P, Mudaliar S. Pioglitazone: side effect and safety profile. Expert Opin Drug Saf. 2010; 9: 347–354. doi: 10.1517/14740331003623218 20175701

4. Bonato JM, Bassani TB, Milani H, Vital MABF, de Oliveira RMW. Pioglitazone reduces mortality, prevents depressive-like behavior, and impacts hippocampal neurogenesis in the 6-OHDA model of Parkinson's disease in rats. Exp Neurol. 2018; 300: 188–200. doi: 10.1016/j.expneurol.2017.11.009 29162435

5. Ridder DA, Schwaninger M. In search of the neuroprotective mechanism of thiazolidinediones in Parkinson's disease. Exp Neurol. 2012; 238: 133–137. doi: 10.1016/j.expneurol.2012.08.012 23085103

6. Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC. Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease. J Neurochem. 2002; 82: 615–624. doi: 10.1046/j.1471-4159.2002.00990.x 12153485

7. Pinto M, Nissanka N, Peralta S, Brambilla R, Diaz F, Moraes CT. Pioglitazone ameliorates the phenotype of a novel Parkinson's disease mouse model by reducing neuroinflammation. Mol Neurodegener. 2016; 11: 25. doi: 10.1186/s13024-016-0090-7 27038906

8. Simuni T, Kieburtz K, Tilley B, Elm JJ, Ravina B, Babcock D, et al. Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial. The Lancet Neurol. 2015; 14: 795–803. doi: 10.1016/S1474-4422(15)00144-1 26116315

9. Brakedal B, Flønes I, Reiter SF, Torkildsen Ø, Dölle C, Assmus J, et al. Glitazone use associated with reduced risk of Parkinson's disease. Mov Disord. 2017; 32: 1594–1599. doi: 10.1002/mds.27128 28861893

10. Brauer R, Bhaskaran K, Chaturvedi N, Dexter DT, Smeeth L, Douglas I. Glitazone treatment and incidence of Parkinson's disease among people with diabetes: A retrospective cohort study. PLoS Med. 2015; 12: e1001854. doi: 10.1371/journal.pmed.1001854 26196151

11. Connolly JG, Bykov K, Gagne JJ. Thiazolidinediones and Parkinson Disease: A Cohort Study. Am J Epidemiol. 2015; 182: 936–944. doi: 10.1093/aje/kwv109 26493264

12. Lin HL, Lin HC, Tseng YF, Chao JC, Hsu CY. Association of thiazolidinedione with a lower risk of Parkinson's disease in a population with newly-diagnosed diabetes mellitus. Ann Med. 2018; 50: 430–436. doi: 10.1080/07853890.2018.1488083 29888974

13. Wu HF, Kao LT, Shih JH, Kao HH, Chou YC, Li IH, et al. Pioglitazone use and Parkinson's disease: a retrospective cohort study in Taiwan. BMJ Open. 2018; 8: e023302. doi: 10.1136/bmjopen-2018-023302 30158237

14. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010; 8:336–341. doi: 10.1016/j.ijsu.2010.02.007 20171303

15. Sterne JA, Herna´n MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; i4919. doi: 10.1136/bmj.i4919 27733354

16. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014; 29:1583–1590. doi: 10.1002/mds.25945 24976103

17. Haaxma CA, Bloem BR, Borm GF, Oyen WJ, Leenders KL, Eshuis S, et al. Gender differences in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2007; 78:819–824. doi: 10.1136/jnnp.2006.103788 17098842

Článek vyšel v časopise


2019 Číslo 10