Cardiometabolic protective mechanisms and efficacy of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) in SLE

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with substantial cardiovascular, metabolic, and renal morbidity. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes (T2D), have demonstrated beneficial effects beyond glucose lowering, including improvements in metabolic, cardiovascular, and renal outcomes. These effects span multiple domains, including glycemic control, body weight and blood pressure reduction, heart failure and atherosclerotic cardiovascular disease outcomes, kidney function preservation, and potential immunomodulatory pathways. This narrative review summarizes the metabolic, cardiovascular, renal, and immunomodulatory effects of SGLT2i relevant to SLE. Evidence from the general population supports cardiometabolic and renal benefits, while observational studies and early-phase trials in SLE and lupus nephritis (LN) suggest potential benefits in selected patients. However, SLE-specific evidence remains limited, and important gaps persist regarding efficacy and safety in active disease. Further studies are needed to define the role of SGLT2i in SLE.