Another Win for SGLT2 Inhibitors in Chronic Kidney Disease

Chronic kidney disease (CKD) affects 14% of the U.S. population and poses substantial risks for end-stage kidney disease, cardiovascular events, and mortality. Despite therapeutic stagnation, sodium-glucose cotransporter 2 (SGLT2) inhibitors have transformed CKD treatment. The EMPA-KIDNEY trial demonstrated that empagliflozin (10 mg daily) significantly reduced disease progression and cardiovascular deaths (hazard ratio 0.72; 95% CI 0.64–0.82).

The EMPA-KIDNEY follow-up trial assessed empagliflozin's impact after discontinuation. Among 4891 participants, event rates nearly doubled compared to the active trial, providing robust data. Post-trial benefit persisted, though attenuated (hazard ratio 0.87; 95% CI 0.76–0.99), with early gains evident at six months (hazard ratio 0.60; 95% CI 0.38–0.93). Unlike the initial trial, post-trial findings revealed benefit even among patients with low urinary albumin-to-creatinine ratios.

The study highlights the carryover effects of SGLT2 inhibitors in CKD progression, with mechanisms potentially involving intraglomerular pressure reduction, sodium and glucose reabsorption modulation, and systemic adaptations. Future research should investigate long-term physiological benefits and optimal combination therapies

Chronic kidney disease (CKD) affects 14% of the U.S. population and poses substantial risks for end-stage kidney disease, cardiovascular events, and mortality. Despite therapeutic stagnation, sodium-glucose cotransporter 2 (SGLT2) inhibitors have transformed CKD treatment. The EMPA-KIDNEY trial demonstrated that empagliflozin (10 mg daily) significantly reduced disease progression and cardiovascular deaths (hazard ratio 0.72; 95% CI 0.64–0.82).

The EMPA-KIDNEY follow-up trial assessed empagliflozin's impact after discontinuation. Among 4891 participants, event rates nearly doubled compared to the active trial, providing robust data. Post-trial benefit persisted, though attenuated (hazard ratio 0.87; 95% CI 0.76–0.99), with early gains evident at six months (hazard ratio 0.60; 95% CI 0.38–0.93). Unlike the initial trial, post-trial findings revealed benefit even among patients with low urinary albumin-to-creatinine ratios.

The study highlights the carryover effects of SGLT2 inhibitors in CKD progression, with mechanisms potentially involving intraglomerular pressure reduction, sodium and glucose reabsorption modulation, and systemic adaptations. Future research should investigate long-term physiological benefits and optimal combination therapies