Therapeutic Advances in Diabetic Kidney Disease

Although sodium glucose co-transporter type 2 (SGLT-2) inhibitors were initially introduced as glucose-lowering medications, it was later discovered that cardiorenal protection is the most important treatment effect of these agents. A triad of landmark trials consistently showed the benefits of SGLT-2 inhibitors on kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD), irrespective of the presence or absence of Type 2 diabetes (T2D). Furthermore, finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that safely and effectively improved cardiorenal outcomes in a large Phase 3 clinical trial program that included >13,000 patients with T2D and a wide spectrum of CKD. These two drug categories have shared and distinct mechanisms of action, generating the hypothesis that an overadditive cardiorenal benefit with their combined use may be biologically plausible. In this article, we describe the mechanism of action, and we provide an overview of the evidence for cardiorenal protection with SGLT-2 inhibitors and the nonsteroidal MRA finerenone in patients with CKD associated with T2D.

Automated summary

Although initially introduced as glucose-lowering medications, it was discovered that the most important treatment effect of SGLT-2 inhibitors is cardiorenal protection. The benefits of SGLT-2 inhibitors on kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD), regardless of the presence or absence of Type 2 diabetes (T2D), have been consistently shown in landmark trials. Additionally, the nonsteroidal MRA finerenone has effectively improved cardiorenal outcomes in a large Phase 3 clinical trial program that included a wide spectrum of CKD patients with T2D.