SGLT-2 Inhibitors: A Deeper Dive into Their Renal Protective Properties beyond Glycemic Control and Proteinuria Reduction
Yu An, Haitao Zhang
Abstract
BACKGROUND: Chronic kidney disease (CKD) is highly prevalent and associated with an increasing burden on patients and the healthcare system. Its complex causes and diverse manifestations pose considerable challenges in slowing disease progression. Over the last few decades, pharmacotherapeutic strategies have primarily focused on reducing albuminuria, managing complications, and alleviating symptoms. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, known for their glycemic control and cardiovascular benefits in diabetic patients, have shown promise in renal protection, offering hope for slowing CKD progression in a broader patient population. SUMMARY: The DAPA-CKD and EMPA-KIDNEY trials have provided compelling evidence that dapagliflozin and empagliflozin reduced the risk of a series of renal events and slowed the chronic decline of estimated glomerular filtration rate in patients with CKD, irrespective of diabetic status. The results of these trials strongly support the notion that SGLT-2 inhibitors are effective in renal protection across CKD patients with diverse primary diseases and in varying CKD risk categories. EMPA-KIDNEY also demonstrated that empagliflozin can potentially slow CKD progression in patients without albuminuria, a finding corroborated by results from several other studies. The long-term cardiorenal benefits of empagliflozin were further demonstrated in the post-trial follow-up sub-study of EMPA-KIDNEY. The synergistic effect of SGLT-2 inhibitors with other drugs that have different mechanisms of action is being researched for broader applications. KEY MESSAGES: Emerging evidence underscores the potential of SGLT-2 inhibitors to benefit a wide range of CKD patients, regardless of causes and albuminuria status. Further research in this area will improve our understanding of the roles of this new class of drug in renal protection and potentially shift the paradigm of CKD management.