Abstract
Background: Diabetes mellitus (DM) increases the risk of Parkinson's disease (PD). However, whether DM medications play a part on that increased PD risk is unclear. We designed this meta-analysis to assess the influence of different oral DM medications on the PD risk in patients with DM.Methods: We searched PubMed, Embase, and CENTRAL databases for relevant studies up until January 2021. We pooled adjusted outcomes to assess the PD risk in patients using different DM medications including sulfonylurea, metformin, glitazones (GTZ), dipeptidyl peptidase-4 inhibitors (DPP4i), and glucagon-like peptide-1 agonists (GLP1a).Results: We included 10 studies in our analysis. Our results indicate a lack of significant association between the PD risk and the use of sulfonylureas (three studies; HR, 1.26; 95% CI, 0.95 to 1.66; I2, 70%; p = 0.11), DPP4i (three studies; HR, 0.69; 95% CI, 0.35 to 1.38; I2, 88%; p = 0.30), metformin (five studies; HR, 1.23; 95% CI, 0.98 to 1.78; I2, 84%; p = 0.13), and GTZ (six studies; HR, 0.88; 95% CI, 0.66 to 1.16; I2, 92%; p = 0.35). After exclusion of a single study in the GTZ analysis, our results indicate a significantly reduced PD risk with GTZ use (HR, 0.78; 95% CI, 0.65 to 0.93; I2, 59%; p = 0.06). Similarly, after the exclusion of a single study, our results indicate a significantly increased PD risk with the use of metformin (HR, 1.50; 95% CI, 1.11 to 2.02; I2, 80%; p = 0.008). We also found a significantly reduced PD risk with the use of GLP1a (two studies; HR, 0.41; 95% CI, 0.19 to 0.87; I2, 0%; p = 0.02).Conclusion: The role of different DM medications on the PD risk remains unclear, and the quality of studies is low. While our analysis suggests a lack of association between the use of metformin, GTZ, DPP4i, and sulfonylureas and the PD risk, metformin (to a higher degree) and GTZ may still increase the risk. Limited data suggest a protective effect of GLP1a on the PD risk.
Highlights
Diabetes mellitus (DM) is a metabolic disorder with a high prevalence worldwide
Twelve articles were excluded because 10 compared the Parkinson’s disease (PD) risk between patients with and without DM and did not focus on specific DM medications [16,17,18,19,20,21,22,23,24,25] and 2 [26, 27] had overlapping data with another one [28]
Our pooled analysis results indicate a significantly reduced PD risk for glucagon-like peptide-1 receptor agonists (GLP1a) users (HR, 0.41; 95% confidence intervals (CIs), 0.19 to 0.87; I2, 0%; p = 0.02) (Figure 6)
Summary
Diabetes mellitus (DM) is a metabolic disorder with a high prevalence worldwide. While some complications like nephropathy, retinopathy, and neuropathy are well-recognized, studies suggest that DM increases the risk of neurodegenerative diseases as well [3, 4]. Recent evidence suggests that metabolic disorders like obesity, diabetes, and metabolic syndrome are independent risk factors for the disease [7]. A metaanalysis of population-based cohort studies has indicated that DM independently increases the PD risk by approximately 38% [8]. Insulin deficiency or resistance leading to a lack of activation of insulin receptors in the brain have been shown to contribute to different neurological disorders including neurodevelopmental syndromes, neoplasms, depression, and neurodegenerative diseases [9]. Diabetes mellitus (DM) increases the risk of Parkinson’s disease (PD).
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