Association between dipeptidyl peptidase-4 inhibitor use and risk of Parkinson’s disease among patients with diabetes mellitus

Background: How a person’s Parkinson disease (PD) risk is affected by dipeptidyl peptidase-4 (DPP-4) inhibitors remains unclear. We evaluated the association of PD risk with use of these inhibitors in individuals diagnosed as having diabetes mellitus (DM). Methods: Individuals diagnosed as having new-onset DM were enrolled into the case group and comparison group, comprising patients who received a DPP-4 inhibitor and a sulfonylurea, respectively. These groups were matched through propensity score matching on the basis of income level, gender, urbanization level, enrollment year, age, and diabetes complications severity index score. The case group was divided into subgroups on the basis of whether they had a cumulative defined daily dose (cDDD) of <75, 75–150, or >150. The DPP-4 inhibitor–PD risk association was evaluated through a Cox proportional hazards model. The Bonferroni adjustment test was employed to adjust P-values and reduce the false positive rate. Results: Compared with those in the comparison group (treatment with a sulfonylurea), patients with a DPP-4 inhibitor cDDD of >150 had a hazard ratio (HR) of 1.30 for PD development (95% confidence interval [CI]: 0.97–1.73; adjusted P =.263); the HRs for patients with a cDDD of <75 or 75–150 were 0.95 (95% CI: 0.71–1.27; adjusted P =.886) and 1.06 (95% CI: 0.75–1.50; adjusted P =.886), respectively. We noted nonsignificant differences regarding the associations between the use of the various DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) and PD risk after adjustment for any individual inhibitor (adjusted P >.05). Conclusions: DPP-4 inhibitors were discovered in this study to not be associated with increased PD risk. This result was confirmed when the analysis was conducted individually for the 4 investigated DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and vildagliptin).