Acute onset of rheumatoid arthritis associated with administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with diabetes mellitus

We describe the first case of a 63-year-old male patient with type 2 diabetes mellitus who was newly diagnosed with definitive rheumatoid arthritis (RA) 2 months after starting medication with a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin. We subsequently performed a survey to determine if other such cases existed among patients who started taking sitagliptin at our university hospital and at hospitals in the Kashiwa and Noda districts. A survey of 147 patients treated with sitagliptin revealed an additional patient whose arthritis was also linked to the use of the DPP-4 inhibitor. This second patient had maintained her RA in a state of remission with diabetes for 15 years; however, 2 months after beginning sitagliptin therapy for control of diabetes, her arthritis relapsed as definitive RA. A recent study on patients with RA and on animals deficient in DPP-4 suggests that a decrease or absence of DPP-4 activity might be associated with cytokine-induced arthritis. On the other hand, a pooled analysis in the United States and a post-marketing monitoring in Japan have revealed that the occurrence of arthritis linked to pharmacologic inhibition of DPP-4 by sitagliptin is rare. Because DPP-4 might possibly be involved in the pathogenesis of RA, and the use of sitagliptin in our cases is linked to activation of RA, it is important to carefully follow patients treated with DPP-4 inhibitor to monitor for onset of RA, although the incidence rate of this adverse event is low.