Clinical Evidence of Kidney Protection Exerted by SGLT2 Inhibitors

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have become foundational therapies for nephroprotection, transforming the management of chronic kidney disease (CKD) beyond the traditional risk factors. This chapter synthesizes evidence from randomized controlled trials and real-world studies demonstrating that SGLT2i consistently reduce albuminuria, slow estimated glomerular filtration rate (eGFR) decline, and lower the risk of hard renal endpoints, including progression to end-stage kidney disease. Early cardiovascular outcome trials first signalled renal benefit as secondary outcomes, which was subsequently confirmed in dedicated renal trials such as CREDENCE, DAPA-CKD, and EMPA-KIDNEY, establishing kidney protection in patients with and without type 2 diabetes and across a broad spectrum of eGFR and albuminuria. Heart failure trials further support renal preservation in high cardiorenal-risk populations. Complementary real-world evidence across multiple health systems corroborates trial findings, extending effectiveness to heterogeneous populations, including older adults and nondiabetic CKD. The chapter also reviews emerging data on combination strategies with GLP-1 receptor agonists or finerenone, long-term treatment considerations, and projections suggesting substantial delays in kidney failure with earlier initiation. Collectively, these data support broad implementation of SGLT2i as core disease-modifying therapy in CKD, while highlighting priority areas for future research in underrepresented populations and optimized combination regimens.