Mathematical Modeling of Renal Effects Mediated by SGLT2 Inhibitors

Sodium–glucose cotransporter 2 (SGLT2) inhibitors confer robust kidney and cardiovascular protection that extends beyond glycemic control, yet the physiological mechanisms remain incompletely understood. This review highlights how mathematical modeling has advanced understanding of SGLT2 inhibitor actions across tubular transport, tubuloglomerular feedback, renal hemodynamics, and oxygen energetics. Models predict that SGLT2 inhibition redistributes nephron transport work, lowers intraglomerular pressure via enhanced macula densa signaling, and produces spatially heterogeneous effects on cortical and medullary oxygen demand. Modeling studies further clarify treatment responses in diabetes, reduced nephron number, and sex-specific transporter architectures, while emerging human-based frameworks link transporter-level inhibition to clinical endpoints. Together, integrative modeling provides a quantitative bridge between molecular targets and cardiorenal outcomes.