Objective This study explores the association between Type 2 diabetes mellitus (T2DM), dipeptidyl peptidase‐4 inhibitors (DPP4i), and rheumatoid arthritis (RA). Methods We conducted a comprehensive analysis using data from the National Health and Nutrition Examination Survey (NHANES), existing studies, and genome‐wide association studies (GWAS). Weighted logistic regression was employed to investigate the association between T2DM and RA. A meta‐analysis was performed to examine the relationship between DPP4i use and the risk of RA. Additionally, a drug target‐mediation mendelian randomization (MR) study was conducted to evaluate the causal relationship between DPP4i and RA, as well as potential pathway mechanisms. Results The NHANES analysis revealed T2DM was associated with RA (OR = 1.31). The meta‐analysis, which included 12 studies, indicated a reduced risk of RA among DPP4i users (RR = 0.63). MR analysis demonstrated that DPP4i use was associated with a decreased risk of RA (OR = 0.84). Mediation MR analysis suggested that DPP4i might influence RA development through immune factors such as CD14 + CD16+ monocytes, CXCL11, and IL‐2 receptors. Conclusions This study confirmed a significant association between T2DM and RA and further revealed that DPP4i might reduce RA risk through inflammation and immune modulation. Further studies are needed to confirm these findings.
Zhang et al. (Thu,) studied this question.