Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection

“…Preliminary evidence supporting combination therapies, namely ETA-RA + SGLT2i or ASI + SGLT2i, set the scene for larger phase III studies examining whether the favorable effects will effectively lower the risk of cardiorenal outcomes in patients with DKD. The safety and tolerability of these new combinations appear acceptable when given on top of standard-of-care treatments [65,66], but these reassuring findings have yet to be confirmed in large-scale clinical trials. Beyond GLP-1 RA alone, the dual GIP/GLP-1 receptor agonist tirzepatide remarkably slowed the progression of DKD in a post hoc analysis of the SURPASS-4 trial [99].…”

“…Very recently, the efficacy of BI 690517, a highly selective ASI, was tested in CKD patients. In a phase II placebo-controlled renal outcome trial, 586 CKD patients were randomized to BI 690517 [66] either as a monotherapy or in combination with empagliflozin. The experimental drug, BI 690517, showed a dose-dependent reduction of albuminuria, and when used on top of empagliflozin exhibited an additive efficacy.…”

Advances in Cardiorenal Medicine; the Year 2023 in Review

“…BI 690517 is a highly selective aldosterone synthase inhibitor that directly lowers aldosterone production, potentially enhancing the effectiveness of current therapies. In a phase-2 multinational RCT, the safety and efficacy of BI 690517 were explored in 586 patients with CKD and urine albumin-to-creatinine ratio of 200-5,000 mg/g who were receiving RAAS blockers [33]. BI 690517 was found to reduce albuminuria, with or without empagliflozin, suggesting an additive efficacy for patients with CKD.…”

Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic

“…How the already established RAASis will perform with novel RAASis is partially yet to be shown. The Asi BI690517, for example, was studied in patients on top of stable ACEi/ARB therapy and showed a favorable safety profile thus far [73]. Whether a combination of ACEis/ARBs with AGT-suppressing medications, which intervene at a very early stage of the RAAS and have a long lasting effect, is safe, will be studied in the upcoming KARDIA-2 trial [74].…”