Repurposing sodium glucose cotransporter-2 (SGLT-2) inhibitors in sarcoidosis: A potential strategy for reducing mortality.

Abstract

Introduction: The renin-angiotensin-aldosterone system (RAAS) plays a key role in sarcoidosis pathogenesis. A recent study suggests that ACE inhibitors may worsen outcomes in sarcoidosis, whereas ARBs may be more beneficial. SGLT2 inhibitors modulate RAAS activity and have anti-inflammatory properties, making them a potential therapeutic option in this population.

Objectives: To evaluate whether the addition of SGLT2 inhibitors to ARB therapy improves long-term survival outcomes in patients with sarcoidosis.

Methods: This retrospective cohort study analyzed adults diagnosed with sarcoidosis from the TrinetX database between 2015 and 2025. Patients receiving ARBs with or without SGLT2 inhibitors were compared following propensity score matching for demographics, comorbidities, and concurrent immunosuppressive therapies.

Results: Patients receiving both ARBs and SGLT2 inhibitors had lower all-cause mortality over five years compared to those on ARBs alone. No significant differences were observed in secondary outcomes such as sepsis, respiratory failure, cardiovascular events, or renal complications.

Conclusion: In patients with sarcoidosis treated with ARBs, the addition of SGLT2 inhibitors was associated with improved long-term survival. These findings support further investigation into the role of SGLT2 inhibitors as adjunctive therapy in sarcoidosis.