Gliptins and Parkinson's disease

A cohort study revealed evidence that the use of DPP-4 inhibitors (gliptins) and/or GLP-1 mimetics is associated with a lower rate of Parkinson's disease compared to the use of other oral antidiabetic drugs (1):

• an inverse association between use of DPP4 inhibitors and GLP-1 mimetics and the onset of Parkinson's disease (incidence rate ratio (IRR) 0.64; 95% CI 0.43-0.88; P < 0.01 and IRR 0.38; 95% CI 0.17-0.60; P < 0.01, respectively)

In a rat model of Parkinson's disease (2):

• sitagliptin and PF-00734,200 (experimental drug that acts as a potent and selective inhibitor of dipeptidyl peptidase-4 (DPP-4) showed beneficial neuroprotective and neuroregenerative actions
  • there was evidence of predominantly peripheral DPP4 inhibitor activity but also brain related DPP4 inhibitor activity

Reference:

1. Brauer R, Wei L, Ma T, Athauda D, Girges C, Vijiaratnam N, Auld G, Whittlesea C, Wong I, Foltynie T. Diabetes medications and risk of Parkinson's disease: a cohort study of patients with diabetes. Brain. 2020 Oct 1;143(10):3067-3076.
2. Yu SJ et al. DPP-4 inhibitors sitagliptin and PF-00734,200 mitigate dopaminergic neurodegeneration, neuroinflammation and behavioral impairment in the rat 6-OHDA model of Parkinson's disease. Geroscience. 2024 Oct;46(5):4349-4371.