SGLT2 inhibitors across the spectrum of chronic kidney disease: a narrative review

Chronic kidney disease (CKD) is a growing public health concern, affecting at least 1 in 7 adults in the United States, and accounting for a large proportion of healthcare spending. The risk of mortality rises steeply with declining kidney function, mostly due to cardiovascular-related deaths. Since CKD is asymptomatic in the early stages, diagnosis is sometimes delayed. However, early diagnosis is important for timely initiation of interventions to reduce disease progression, and to avoid the need for hospitalizations, dialysis, or kidney transplantation. This review focuses on the impact of sodium glucose transporter 2 inhibitors (SGLT2i) on CKD based on mechanistic and clinical trial evidence. These agents affect the kidneys through changes in sodium transport and metabolic factors that interfere with the primary pathological mechanisms shared by most kidney diseases. Following clinical trials of SGLT2i in patients with type 2 diabetes which demonstrated reductions in the risk of major adverse CV events, death, and hospitalizations for heart failure (HHF), and in patients with heart failure (HF) with and without diabetes which showed reductions in death and HHF, recent trials in patients with CKD have provided overwhelming support for the use of SGLT2i as foundational therapy across a broad spectrum of patients with CKD, regardless of diabetes status, primary kidney disease (except polycystic kidney disease), or kidney function. While clinical trials in CKD generally recruit patients with a high risk of events, patients at lower risk could also benefit from SGLT2i in terms of reduction of CKD progression, HF and death, as well as other beneficial effects including reductions in blood sugar, body weight and blood pressure.