Sodium Glucose Co-Transporter-2 inhibitors in patients with systemic sclerosis with or without heart failure.

Background: Patients with systemic sclerosis are at heightened risk of developing heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown cardio-renal benefits in diverse populations with cardio-renal dysfunction, but their impact on outcomes in patients with systemic sclerosis has not been described.

Methods: This retrospective cohort study used the Research Network of the TriNetX platform to compare outcomes between patients with systemic sclerosis prescribed with SGLT2 inhibitors versus those without SGLT2i prescription, using data from January 1, 2013, to May 6, 2025. Following propensity score matching, each cohort included 1,402 patients with balanced baseline characteristics (standardized mean differences <0.2). The primary outcome was all-cause mortality. Secondary outcomes included first-time heart failure diagnosis, acute heart failure, acute myocardial infarction, hospitalization, stroke, cardiac arrest, and chronic kidney disease.

Results: SGLT2i prescription was associated with a significantly lower risk of all-cause mortality (Hazard Ratio [HR] 0.54, 95 % confidence interval [CI] 0.44-0.66), stroke (HR 0.64, 95 % CI 0.42-0.96), and hospitalization (HR 0.76, 95 % CI 0.66-0.86). Notably, patients without a history of heart failure (HR 0.62, 95 % CI 0.45-0.87) and patients with a history of heart failure also had a lower risk of hospitalization (HR 0.76, 95 % CI 0.57-1.00). No significant differences were observed in the risks of major adverse cardiovascular events, acute myocardial infarction, or chronic kidney disease.

Conclusion: In this real-world analysis, SGLT2 inhibitors were associated with reduced mortality, stroke, and hospitalization in patients with systemic sclerosis, supporting their potential therapeutic role in this population.