Finerenone with empagliflozin in CKD with diabetes (CONFIDENCE): only a blood pressure effect? Likely!

Chronic kidney disease (CKD) in persons with diabetes mellitus (DM) continues to be the leading cause of end-stage kidney disease (ESKD) worldwide. Despite the use of reninangiotensin system blockade, sodium-glucose transport protein 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists the risk of progression to ESKD and CV events persists in this high-risk population. For this reason, new or combined strategies for treating persons with CKD and DM are in constant development. This editorial discusses the results of a recent published trial, Combination Effect of Finerenone and Empagliflozin (EMP) in Participants with Chronic Kidney Disease and Type 2 Diabetes Using a Urinary Albumin-to-Creatinine Ratio (UACR) Endpoint (CONFIDENCE) in persons with DM and CKD focused in the mechanisms involved in the beneficial renal effect in terms of albuminuria reduction[1]. Whether there is related to the synergistic effect of the combination therapy (EMP + finerenone) or merely a manifestation secondary to systolic blood pressure (SBP) reduction remains to be determined[2].The CONFIDENCE trial, a double-blind, multicenter, study involving 800 patients with type 2 DM and CKD (eGFR 30 to 90 ml/min/1.73m 2 and urinary albumin-to creatinine ratio (UACR) 100 to < 5000 mg/g) tested the effect of combining finerenone and EMP on reducing albuminuria compared with monotherapy with either empagliflozin or finerenone alone, over 180 days. All patients were on maximum tolerated angiotensin II blockade at baseline. The primary endpoint was the relative change in the log-transformed mean UACR from baseline to 180 days, a surrogate marker for kidney disease progression in previous meta-analysis [3].