SGLT2 Inhibitors and Finerenone: A friendly Duo in the Treatment of Diabetic Kidney Disease?

Abstract

For decades, achieving glycemic control, target blood pressure, and renin-angiotensin-aldosterone system (RAAS) blockade remained to be the therapeutic interventions for retarding diabetic kidney disease (DKD) progression. The management of DKD showed major transformation when SGLT2 inhibitors were recommended to reduce the risk of progressive deterioration in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), and renal death following results of CREDENCE and DAPA-CKD trials. Despite currently available therapeutic approaches, the risk of cardiac death, progression to ESRD, and requirement of renal replacement therapy remains high. Finerenone is the newer potent selective nonsteroidal mineralocorticoid receptor antagonist (MRA) that showed reduction in primary composite renal and CV outcomes in FIDELIO-DKD and FIGARO-DKD studies, respectively. While SGLT2 inhibitors have direct effects on cellular and metabolic functions besides reduction in glomerular hyperfiltration, finerenone primarily inhibits mineralocorticoid pathway-dependent inflammation and fibrosis. The renal benefits of dapagliflozin in the DAPA-CKD trial were regardless of MRA, and likewise, the benefits of finerenone in FIDELIO and FIGARO studies were irrespective of SGLT2i. Moreover, the risk of serious hyperkalemia with MRA was significantly reduced by concomitant use of SGLT2 inhibitors, making this combination a safer choice. Even though available data support the fact that this duo possibly has distinct as well as complementary mechanisms in protecting renal and cardiac functions, strong evidence to recommend routine use of the combination of SGLT2 inhibitors and MRA in DKD is currently lacking. However, the results of the ongoing CONFIDENCE study evaluating superiority of dual therapy of empagliflozin and finerenone will be worthwhile to understand the benefits of this friendly duo.