# Assessing the Association Between T2DM, Rheumatoid Arthritis, and Dipeptidyl Peptidase‐4 Inhibitors: Insights From Epidemiology, Meta‐Analysis, and Mendelian Randomization Study

## TL;DR

This study finds that Type 2 diabetes is linked to rheumatoid arthritis and suggests that a diabetes drug may lower arthritis risk by reducing inflammation.

## Contribution

The novel contribution is identifying a potential causal link between DPP4 inhibitors and reduced RA risk through immune modulation.

## Key findings

- T2DM is associated with a 31% increased risk of rheumatoid arthritis.
- DPP4 inhibitors are linked to a 37% reduced risk of rheumatoid arthritis.
- DPP4 inhibitors may reduce RA risk by modulating immune factors like CD14+ CD16+ monocytes and IL-2 receptors.

## Abstract

This study explores the association between Type 2 diabetes mellitus (T2DM), dipeptidyl peptidase‐4 inhibitors (DPP4i), and rheumatoid arthritis (RA).

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.

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.

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.