What have we learned about renal protection from the cardiovascular outcome trials and observational analyses with SGLT2 inhibitors?

Abstract

Over the past 5 years, sodium-glucose cotransport 2 (SGLT2) inhibitors have been increasingly regarded as glycaemic agents with cardiovascular (CV) and renal protective effects. The CV benefits of SGLT2 inhibitors have been well established in patients with type 2 diabetes (T2D) and a range of CV comorbidities at baseline. Subsequently, the renal benefits of SGLT2 inhibitors were established in the CREDENCE trial, a dedicated renal outcome trial where canagliflozin reduced the primary composite renal outcome by 30%. In light of these trials, clinical practice guidelines have rapidly evolved, recommending the use of SGLT2 inhibitors as renal and cardioprotective agents in appropriate patient populations. Accordingly, it is important to have an in-depth understanding of the evidence underlying the use of SGLT2 inhibitors in patients with T2D based on published clinical trials and real-world evidence (RWE) studies, as well as information related to potential safety concerns. To accomplish this, we reviewed the evidence for renal protection and safety with SGLT2 inhibitors in the EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58 CV safety trials, and in the growing body of evidence emerging from real-world studies. This body of work has shown that SGLT2 inhibitors reduce the risk of surrogate renal endpoints such as albuminuria and mitigate the risk of hard renal endpoints including doubling of serum creatinine and end-stage kidney disease in patients with T2D.

Keywords: SGLT2 inhibitor; diabetic nephropathy.