Esaxerenone at 1.25, 2.5, and 5 mg/d added to a renin-angiotensin system inhibitor significantly reduced urinary albumin-to-creatinine ratio by 38%, 50%, and 56%, respectively, compared to 7% with placebo in patients with type 2 diabetes and microalbuminuria.
RCT (n=365)
Double-blind
Dynamic allocation (minimization method)
Yes
Does esaxerenone reduce urinary albumin-to-creatinine ratio in Japanese patients with type 2 diabetes mellitus and microalbuminuria on a renin-angiotensin system inhibitor?
Adding the nonsteroidal mineralocorticoid receptor blocker esaxerenone to an ongoing renin-angiotensin system inhibitor significantly and dose-dependently reduces albuminuria in patients with type 2 diabetes and microalbuminuria.
Effect estimate: Geometric LS mean ratio 0.5 (95% CI 0.4 to 0.6)
Absolute Event Rate: -56% vs -7%
p-value: p=<0.001
Background and objectives The progression of kidney disease in some patients with type 2 diabetes mellitus may not be adequately suppressed by renin-angiotensin system inhibitors. Esaxerenone (CS-3150) is a nonsteroidal mineralocorticoid receptor blocker that has shown kidney protective effects in preclinical studies, and it is a potential add-on therapy to treat diabetic kidney disease. This phase 2 study evaluated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes mellitus and microalbuminuria. Design, setting, participants, all P <0.001). The urinary albumin-to-creatinine ratio remission rate (defined as urinary albumin-to-creatinine ratio <30 mg/g creatinine at the end of treatment and ≥30% decrease from baseline) was 21% in the 2.5- and 5-mg/d groups versus 3% for placebo (both P <0.05). Adverse events occurred slightly more frequently with esaxerenone versus placebo, but the frequencies of drug-related adverse events and discontinuation rates were similar in the placebo and the 0.625-, 1.25-, and 2.5-mg/d groups. Drug-related adverse events and treatment discontinuations were marginally higher in the 5-mg/d group. The most common drug-related adverse event was hyperkalemia, which was dose proportional. Conclusions Adding esaxerenone at 1.25, 2.5, and 5 mg/d for 12 weeks to an ongoing renin-angiotensin system inhibitor significantly reduces urinary albumin-to-creatinine ratio in patients with type 2 diabetes mellitus and microalbuminuria.
Ito et al. (Thu,) conducted a rct in Type 2 Diabetes with Microalbuminuria (n=365). Esaxerenone (CS-3150) vs. Placebo was evaluated on Change in urinary albumin-to-creatinine ratio (UACR) from baseline to week 12 (Geometric LS mean ratio 0.5, 95% CI 0.4 to 0.6, p=<0.001). Esaxerenone at 1.25, 2.5, and 5 mg/d added to a renin-angiotensin system inhibitor significantly reduced urinary albumin-to-creatinine ratio by 38%, 50%, and 56%, respectively, compared to 7% with placebo in patients with type 2 diabetes and microalbuminuria.