Chronic Kidney Disease and SGLT2 Inhibitors: A Review of the Evolving Treatment Landscape

There is currently an unmet need for effective treatment of chronic kidney disease (CKD) that slows disease progression, prevents development of end-stage kidney disease and cardiovascular disease, and prolongs survival of patients with CKD. In the last 20 years, the only agents to show a reduction in the risk of CKD progression in patients with and without type 2 diabetes (T2D) were angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, but neither drug class has provided a decreased risk of all-cause mortality in patients with CKD and evidence for their use in patients with CKD without T2D is relatively limited. This review discusses the mechanisms underlying the progression of CKD, its associated risk factors, and summarizes the potential therapeutic approaches for managing CKD. There is increasing evidence to support the role of sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy in patients with CKD, including data from the designated kidney outcome trials in patients with T2D (CREDENCE) and in patients with or without T2D (DAPA-CKD). These studies showed a significant reduction in the risk of CKD progression with canagliflozin (in patients with T2D) or dapagliflozin (in patients with or without T2D), respectively, with DAPA-CKD being the first trial to show a reduced risk of all-cause mortality. On the basis of these data, individualized treatment with SGLT2 inhibitors represents a promising therapeutic option for patients with diabetic and nondiabetic CKD to slow disease progression.