Type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA) are chronic conditions with overlapping inflammatory and metabolic features. An analysis published in the Journal of Diabetes Research evaluated the association between T2DM and RA and assessed whether dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are linked to RA risk.

The study combined multiple analytical approaches. Data from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate the association between T2DM and RA using weighted logistic regression. A meta-analysis of 12 studies examined the relationship between DPP-4 inhibitor use and RA risk. In addition, a drug target-mediation Mendelian randomization (MR) analysis assessed genetic evidence related to DPP-4 inhibitor targets and RA risk.

The NHANES analysis showed that T2DM was associated with RA with an odds ratio of 1.31. The meta-analysis reported that DPP-4 inhibitor users had lower RA risk compared with non-users (relative risk = 0.63). The Mendelian randomization analysis found that DPP-4 inhibitor exposure was associated with decreased RA risk (odds ratio = 0.84).

Further mediation MR analysis evaluated immune-related factors potentially involved in the association. The analysis identified CD14⁺, CD16⁺ monocytes, CXCL11, and interleukin-2 receptors among the immune markers assessed in the evaluated pathways. Overall, the analysis reported an association between T2DM and RA and identified relationships between DPP-4 inhibitor use and RA risk that warrant further investigation.