Skip to main content

Advertisement

SpringerLink
Log in

Thiazolidinedione use is associated with reduced risk of Parkinson’s disease in patients with diabetes: a meta-analysis of real-world evidence

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Background

The thiazolidinedione (TZD) class of oral antidiabetic agents are used to treat type 2 diabetes mellitus (DM). This meta-analysis aimed to understand the protective effect of TZD on Parkinson’s disease (PD) in people with diabetes.

Method

A literature search was performed in PubMed, Embase, and Cochrane central from inception to until 30 September 2019. We included all real-world evidence studies assessing the use of TZD class of drugs and the risk of PD in people with diabetes. Quality of the studies was evaluated using the Newcastle-Ottawa scale. The primary outcome was the pooled hazard ratio (HR) of PD among type 2 DM TZD users as compared with TZD non-users in people with diabetes. The secondary outcome was the HR of PD among type 2 DM TZD users as compared with non-users (include both diabetic and nondiabetic population). Meta-analysis was performed using RevMan software.

Results

Out of five studies selected for inclusion, four studies fulfilled the criteria for primary outcomes. The participants’ mean age and follow-up duration were 66.23 ± 9.59 years and 5.25 years (2.97–7.9 years), respectively. There was a significant reduction in the risk of PD (pooled adjusted HR of 0.81 [95% CI 0.70–0.93, p = 0.004]) in TZD users compared with non-TZD users in people with diabetes. A significant protective effect of TZD was observed in Caucasian population (3 studies) (HR 0.78 (95% CI 0.66–0.92), p = 0.003).

Conclusion

This meta-analysis demonstrates a potential neuroprotective effect of TZD for PD risk in the population with DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T (2016) The incidence of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology 46:292–300

    Article  Google Scholar 

  2. Hobson P, Meara J (2018) Mortality and quality of death certification in a cohort of patients with Parkinson’s disease and matched controls in North Wales, UK at 18 years: a community-based cohort study. BMJ Open 8:e018969

    Article  Google Scholar 

  3. Statistics. Parkinson’s Foundation. Available at: https://www.parkinson.org/Understanding-Parkinsons/Statistics. Accessed on 10th July 2019

  4. Moisan F, Kab S, Mohamed F, Canonico M, le Guern M, Quintin C, Carcaillon L, Nicolau J, Duport N, Singh-Manoux A, Boussac-Zarebska M, Elbaz A (2016) Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J Neurol Neurosurg Psychiatry 87:952–957

    Article  Google Scholar 

  5. Johnson SJ, Diener MD, Kaltenboeck A, Birnbaum HG, Siderowf AD (2013) An economic model of Parkinson’s disease: implications for slowing progression in the United States. Mov Disord 28:319–326

    Article  Google Scholar 

  6. Kowal SL, Dall TM, Chakrabarti R, Storm MV, Jain A (2013) The current and projected economic burden of Parkinson’s disease in the United States. Mov Disord 28:311–318

    Article  Google Scholar 

  7. Velikova G, Valderas JM, Potter C et al (2017) Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: advances in patient reported outcomes research. Health Qual Life Outcomes 15:185

    Article  Google Scholar 

  8. Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC (2002) Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson’s disease. J Neurochem 82:615–624

    Article  CAS  Google Scholar 

  9. Dehmer T, Heneka MT, Sastre M, Dichgans J, Schulz JB (2004) Protection by pioglitazone in the MPTP model of Parkinson’s disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J Neurochem 88:494–501

    Article  CAS  Google Scholar 

  10. Hunter RL, Choi DY, Ross SA, Bing G (2008) Protective properties afforded by pioglitazone against intrastriatal LPS in Sprague-Dawley rats. Neurosci Lett 432:198–201

    Article  CAS  Google Scholar 

  11. Swanson CR, Joers V, Bondarenko V, Brunner K, Simmons HA, Ziegler TE, Kemnitz JW, Johnson JA, Emborg ME (2011) The PPAR-gamma agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys. J Neuroinflammation 8:91

    Article  CAS  Google Scholar 

  12. Brakedal B, Flønes I, Reiter SF, Torkildsen Ø, Dölle C, Assmus J, Haugarvoll K, Tzoulis C (2017) Glitazone use associated with reduced risk of Parkinson’s disease. Mov Disord 32:1594–1599

    Article  CAS  Google Scholar 

  13. Connolly JG, Bykov K, Gagne JJ (2015) Thiazolidinediones and Parkinson disease: a cohort study. Am J Epidemiol 182:936–944

    Article  Google Scholar 

  14. Kmietowicz Z (2015) Glitazones are associated with reduced risk of Parkinson’s disease. Bmj 351:h3949

    Article  Google Scholar 

  15. Lin H-L, Lin H-C, Tseng Y-F, Chao JC-J, Hsu C-Y (2018) Association of thiazolidinedione with a lower risk of Parkinson’s disease in a population with newly-diagnosed diabetes mellitus. Ann Med 50:430–436

    Article  CAS  Google Scholar 

  16. 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:e1001854

    Article  Google Scholar 

  17. Wu H-F, Kao L-T, Shih J-H et al (2018) Pioglitazone use and Parkinson’s disease: a retrospective cohort study in Taiwan. BMJ Open 8:e023302

    Article  Google Scholar 

  18. NINDS Exploratory Trials in Parkinson Disease (NET‐PD) FS‐ZONE Investigators (2015) Pioglitazone in early Parkinson’s disease: a phase 2, multicentre, double-blind, randomised trial. The Lancet Neurology 14:795–803

  19. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269

    Article  Google Scholar 

  20. Hussain S, Singh A, Rahman SO, Habib A, Najmi AK (2018) Calcium channel blocker use reduces incident dementia risk in elderly hypertensive patients: a meta-analysis of prospective studies. Neurosci Lett 671:120–127

    Article  CAS  Google Scholar 

  21. Singh A, Hussain S, Najmi AK (2017) Number of studies, heterogeneity, generalisability, and the choice of method for meta-analysis. J Neurol Sci 381:347

    Article  Google Scholar 

  22. Carta AR, Simuni T (2015) Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson’s disease. Expert Opin Investig Drugs 24:219–227

    Article  CAS  Google Scholar 

  23. Ghosh A, Tyson T, George S et al (2016) Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson’s disease. Science Translational Medicine 8:368ra174

    Article  Google Scholar 

  24. Wang Y, Zhao W, Li G et al (2017) Neuroprotective effect and mechanism of thiazolidinedione on dopaminergic neurons in vivo and in vitro in Parkinson’s disease. PPAR Res 2017:4089214

    PubMed  PubMed Central  Google Scholar 

  25. Schernhammer E, Hansen J, Rugbjerg K, Wermuth L, Ritz B (2011) Diabetes and the risk of developing Parkinson’s disease in Denmark. Diabetes Care 34:1102–1108

    Article  Google Scholar 

  26. Santiago JA, Potashkin JA (2013) Shared dysregulated pathways lead to Parkinson’s disease and diabetes. Trends Mol Med 19:176–186

    Article  CAS  Google Scholar 

  27. Aviles-Olmos I, Limousin P, Lees A, Foltynie T (2013) Parkinson’s disease, insulin resistance and novel agents of neuroprotection. Brain 136:374–384

    Article  Google Scholar 

  28. Athauda D, Foltynie T (2016) Insulin resistance and Parkinson’s disease: a new target for disease modification? Progress in Neurobiology 145–146:98–120

    Article  Google Scholar 

  29. Hogg E, Athreya K, Basile C, Tan EE, Kaminski J, Tagliati M (2018) High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Park Dis 8:259–265

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Medicine (Division of Pharmacology), School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

    Salman Hussain

  2. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia

    Ambrish Singh, Bruce Taylor, John Burgess & Benny Antony

  3. Independent Researcher, New Delhi, India

    Harveen Baxi

  4. Department of Neurology, Royal Hobart Hospital, Hobart, Australia

    Bruce Taylor

  5. Department of Endocrinology, Royal Hobart Hospital, Hobart, Australia

    John Burgess

Authors
  1. Salman Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ambrish Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harveen Baxi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bruce Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John Burgess
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Benny Antony
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benny Antony.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 29 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hussain, S., Singh, A., Baxi, H. et al. Thiazolidinedione use is associated with reduced risk of Parkinson’s disease in patients with diabetes: a meta-analysis of real-world evidence. Neurol Sci 41, 3697–3703 (2020). https://doi.org/10.1007/s10072-020-04494-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-020-04494-3

Keywords

Search

Navigation