Glucagon-like peptide-1 receptor analog use is associated with reduced thromboembolic events compared with dipeptidyl peptidase-4 inhibitors in rheumatoid arthritis patients: A global retrospective cohort study.

Abstract

Objective: Rheumatoid arthritis (RA) is an inflammatory disease associated with thromboembolic events. Glucagon-like peptide-1 (GLP-1) analogs, which are used in type 2 diabetes mellitus (T2DM), have shown potential anti-inflammatory effects, but their role in thrombotic events in RA is less clear. This study compares GLP-1 analogs to dipeptidyl peptidase 4 inhibitors (DPP4i) regarding thromboembolic events in RA.

Methods: We performed a retrospective cohort study using TriNetX database to evaluate adult patients who carried the diagnosis of RA from January 1, 2006 to December 1, 2024 with co-existing T2DM and who initiated GLP-1 analogs or DPP4i after diagnosis of RA and T2DM. Patients were divided into two cohorts (GLP-1 vs. DPP4i), and the primary outcome was all thromboembolic events (cerebral infarction, myocardial infarction [MI], deep vein thrombosis [DVT], pulmonary embolism [PE]) within 5 years after GLP-1 analog or DPP4i start. Secondary outcomes included individual events, arterial and venous thrombosis, and all-cause mortality. Propensity score matching adjusted for demographic, clinical, and treatment variables.

Results: We analyzed 41,153 patients, including 25,425 GLP-1 analog and 15,728 DPP4i users, and compared 8,697 matched patients in each group. The median age at medication start was 65 years old, with 70% females. GLP-1 analog users had a 24% lower risk of all thrombotic events (hazard ratio [HR], 0.76 [95% CI: 0.70, 0.83]; p < 0.0001), as well as reduced risks of individual events and an overall lower mortality.

Conclusion: Compared to DPP4i, GLP-1 analogs may lower the risk of thromboembolic events and reduce all-cause mortality in RA patients with T2DM. Key Points • The study identified significantly reduced risks in both arterial and venous thrombosis in RA patients receiving GLP-1 analogs compared with DPP4i. • RA patients who received GLP-1 analogs had lower all-cause mortality compared to those receiving DPP4i. • These findings support potential dual benefit of GLP-1 analogs in reducing inflammation and thrombosis in RA patients with diabetes.