SAT-413 Does Dipeptidyl Peptidase-4 Inhibitor Exacerbate Graves’ Disease?

[Background] Dipeptidyl peptidase-4 (DPP-4) is expressed as CD26 on the surface of immune cells including T cells, suggesting that inhibition of DPP-4 may affect the immune system (1). Actually, DPP-4 inhibitor (DPP-4i)-induced polyarthritis and bullous pemphigoid have been reported (2, 3). It has also been reported that the prevalence of Hashimoto’s thyroiditis was significantly higher in patients on DPP-4i treatment (4). However, relationships between DPP-4i and Graves’ disease has been unclear. [Methods] To investigate the impact of DPP-4i administration on the activity of Graves’ disease, we conducted a multicenter observational trial that included patients with both Graves’ disease and type 2 diabetes mellitus who were administered an oral hypoglycemic agent (OHA) including DPP-4i from December in 2009 to April in 2018. Patients who had systemic diseases affecting thyroid function and those who underwent thyroidectomy or radioiodine treatment within 6 months before or after OHA administration were excluded. Exacerbation of Graves’ disease was defined as an increase in antithyroid drug dose within 6 months after OHA administration. The trial was approved by the institutional review board of Hokkaido University Hospital. [Results] Eighty-three patients were enrolled in the study, and they were divided into an exacerbation group (n = 18) and a non-exacerbation group (n = 65). Comparing baseline characteristics, the percentage of DPP-4i administration was higher in the exacerbation group (83.3%) than in the non-exacerbation group (32.3%) (p = 0.0001). Mean age was also significantly higher in the exacerbation group (p = 0.04), and the duration of Graves’ disease was significantly shorter (p = 0.01). Multivariate logistic regression analysis using factors extracted by comparing baseline characteristics demonstrated a significant association between DPP-4i administration and Graves’ disease exacerbation (odds ratio 5.62, 95% confidence interval 1.16–27.0, p = 0.02). [Conclusion] The current study suggests that DPP-4i administration is associated with exacerbation of Graves’ disease. Reference: (1) Morimoto C et al., Immunol Rev. 1998 Feb;161:55–70. (2) Yokota K et al., Intern Med. 2012;51(15):2041–4. (3) Yoshiji S et al. J Diabetes Investig. 2018 Mar;9(2):445–447. (4) Kridin K et al. Immunol Res. 2018 Jun;66(3):425–430.