Do oral antidiabetic medications alter the risk of Parkinson's disease? An updated systematic review and meta-analysis

Neurol Sci. 2023 Dec;44(12):4193-4203. doi: 10.1007/s10072-023-06965-9. Epub 2023 Jul 27.

Abstract

Background: Diabetes mellitus is a known risk factor for Parkinson's disease (PD), but does this risk vary with antidiabetic medications is still unclear. This meta-analysis aims to compile evidence from the literature to assess the risk of idiopathic PD with various oral antidiabetic medications.

Methods: Databases PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched till 5th April 2023. Adjusted outcomes were pooled to generate a hazard ratio (HR) on the risk of PD with different antidiabetic medications.

Results: Fifteen studies with 2,910,405 diabetic patients were eligible. Pooled analysis failed to show any significant difference in the risk of PD among users of metformin (HR: 1.05 95% CI: 0.91, 1.22 I2 = 81%), glitazones (HR: 0.84 95% CI: 0.68, 1.05 I2 = 91%), glucagon-like peptide-1 agonists (HR: 0.63 95% CI: 0.26, 1.55 I2 = 33%), and sulfonylureas (HR: 1.13 95% CI: 0.96, 1.32 I2 = 76%). However, a meta-analysis of four studies showed that dipeptidyl peptidase-4 inhibitor use was associated with reduced risk of PD in diabetics (HR: 0.69 95% CI: 0.56, 0.86 I2 = 46%). Insufficient data was available on sodium-glucose cotransporter-2 inhibitors, α-glucosidase inhibitors, and glinides.

Conclusions: Limited retrospective evidence indicates that DPP4i may reduce the risk of idiopathic PD in diabetics. Metformin, sulfonylureas, glucagon-like peptide-1 agonists, and glitazones were not associated with any change in the risk of PD. Further studies taking into confounding factors and using a common comparator group are needed to strengthen present evidence.

Keywords: Diabetes; Hypoglycemics; Metformin; Neurodegenerative disease.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Glucagon-Like Peptide 1
  • Humans
  • Hypoglycemic Agents* / adverse effects
  • Metformin / adverse effects
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / epidemiology
  • Retrospective Studies
  • Sulfonylurea Compounds / adverse effects
  • Thiazolidinediones / adverse effects

Substances

  • Glucagon-Like Peptide 1
  • Hypoglycemic Agents
  • Metformin
  • Sulfonylurea Compounds
  • Thiazolidinediones