Abstract Rationale Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) experience significant cardiopulmonary morbidity. Emerging evidence suggests sodium-glucose cotransporter-2 inhibitors (SGLT2i) may confer cardiovascular and survival benefits through pleiotropic mechanisms, yet their role in RA-ILD remains unclear. Methods We performed a retrospective, multicenter cohort study using the TriNetX U.S. Collaborative Network, which aggregates de-identified electronic health records from 109 healthcare organizations. Adults with RA-ILD and type 2 diabetes were categorized by SGLT2i exposure (dapagliflozin or empagliflozin) versus no exposure. Propensity-score matching (1:1) was applied to balance demographics, comorbidities, and cardiometabolic factors, yielding 452 patients in each group. Outcomes were assessed ≥180 days after index diagnosis and included all-cause mortality and major adverse cardiovascular events (MACE: myocardial infarction, stroke, cardiac arrest, or death). Measures of association and Kaplan-Meier analyses were conducted within the TriNetX analytic environment. Results After matching, cohorts were well balanced for age (70.4 ± 9.7 vs 70.6 ± 12.3 years), sex (61% female), and comorbid burden. SGLT2i use was associated with a numerically lower risk of all-cause mortality compared with non-users (11.7% vs 13.1%; odds ratio 0.89, 95% CI 0.60-1.32; p = 0.55). Kaplan-Meier analysis demonstrated improved survival among SGLT2i users (five-year survival 72.2% vs 19.4%; log-rank p = 0.032; hazard ratio 0.67, 95% CI 0.46-0.97). Rates of MACE were similar between groups (22.8% vs 18.8%; OR 1.27, 95% CI 0.92-1.76; p = 0.14), with a neutral effect on event-free survival (HR 0.95, 95% CI 0.71-1.26). No significant differences were observed in hospitalization frequency or event recurrence. Conclusions In this national real-world cohort of patients with RA-ILD and diabetes, SGLT2 inhibitor therapy was associated with improved long-term survival but did not significantly alter cardiovascular event rates. These findings support a potential mortality benefit independent of cardiovascular endpoints and warrant prospective validation to clarify mechanistic pathways in RA-ILD. This abstract is funded by: None
Torres et al. (Fri,) studied this question.