Aims: Dipeptidyl peptidase-4, a transmembrane glycoprotein expressed in various cell types, serves as a co-stimulator molecule to influence immune response. This study aimed to investigate associations between DPP-4 inhibitors and risk of autoimmune disorders in patients with type 2 diabetes mellitus in Taiwan. Methods: This retrospective cohort study used the nationwide data from the diabetes subsection of Taiwan National Health Insurance Research Database between January 1, 2009, and December 31, 2013. Cox proportional hazards models were developed to compare the risk of autoimmune disorders and the subgroup analyses between the DPP-4i and DPP-4i-naïve groups. Results: A total of 774,198 type 2 diabetic patients were identified. The adjusted HR of the incidence for composite autoimmune disorders in DPP-4i group was 0.56 (95% CI 0.53–0.60; P < 0.001). The subgroup analysis demonstrated that the younger patients (aged 20–40 years: HR 0.47, 95% CI 0.35–0.61; aged 41–60 years: HR 0.50, 95% CI 0.46–0.55; aged 61–80 years: HR 0.63, 95% CI 0.58–0.68, P = 0.0004) and the lesser duration of diabetes diagnosed (0–5 years: HR 0.48, 95% CI 0.44–0.52; 6–10 years: HR 0.48, 95% CI 0.43–0.53; ≧ 10 years: HR 0.86, 95% CI 0.78–0.96, P < 0.0001), the more significant the inverse association of DPP-4 inhibitors with the incidence of composite autoimmune diseases. Conclusions: DPP-4 inhibitors are associated with lower risk of autoimmune disorders in type 2 diabetes mellitus patients in Taiwan, especially for the younger patients and the lesser duration of diabetes diagnosed. The significant difference was found between the four types of DPP-4 inhibitors and the risk of autoimmune diseases. This study provides clinicians with useful information regarding the use of DPP-4 inhibitors for treating diabetic patients.
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