A39-23 Association Between GLP 1 Receptor Agonists Use and Interstitial Lung Disease Incidence in Rheumatoid Arthritis With Type 2 Diabetes: A Real-world Cohort Analysis

Abstract Introduction Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely prescribed for type 2 diabetes mellitus (DMII) and have demonstrated anti-inflammatory, metabolic, and anti-fibrotic effects in both experimental and clinical settings. Interstitial lung disease (ILD) is a major extra-articular manifestation of rheumatoid arthritis (RA) associated with substantial morbidity and mortality. Given the shared inflammatory and fibrotic pathways between metabolic disease and RA-ILD, we investigated whether GLP1RA use is associated with a lower incidence of ILD among patients with RA and DMII. Methods A retrospective cohort analysis was conducted using the TriNetX network, encompassing U.S. healthcare organizations from 2010 to 2020. Adults (≥18 years) with RA and DMII were identified and divided into two cohorts: those prescribed GLP1RA (liraglutide, semaglutide, dulaglutide, exenatide, lixisenatide, or tirzepatide) within 3 years before or after both diagnoses and those without GLP1RA use. Propensity score matching (1:1) controlled for demographics, comorbidities, medications, and laboratory markers. Primary outcomes were overall ILD and fibrotic ILD incidence at 10 years. All-cause mortality was evaluated as a secondary outcome. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated. Results After propensity score matching, approximately 3,209 patients were included in each cohort. The incidence of ILD was numerically lower in GLP1RA users but did not reach statistical significance (HR 0.78; 95% CI 0.59-1.03; p = 0.08), as was the case for fibrotic ILD (HR 0.81; 95% CI 0.60-1.09; p = 0.17). Mortality was significantly reduced among GLP1RA users (HR 0.64; 95% CI 0.56-0.74; p 0.001), with a risk of death of 10.7% versus 16.5% and overall survival of 89.3% versus 83.5%, respectively, an absolute survival benefit of 5.8%. Median follow-up duration was approximately 4 to 5 years. Conclusions In this large, real-world cohort, GLP1RA therapy in patients with RA and DMII was not significantly associated with lower ILD or fibrotic ILD incidence but was linked to reduced all-cause mortality. Whether this reflects a true protective effect or residual confounding remains uncertain. These findings highlight the need for prospective and mechanistic studies to clarify the potential systemic and pulmonary effectsof GLP1RAs in RA. This abstract is funded by: None