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Design setting participants & measurements This multicenter randomized double-blind placebo-controlled trial enrolled 365 hypertensive or normotensive patients with type 2 diabetes mellitus and microalbuminuria (urinary albumin-to-creatinine ratio ≥45 to <300 mg/g creatinine) treated with renin-angiotensin system inhibitor who had eGFR≥30 ml/min per 1.73 m2. Participants were randomized to receive 0.625 1.25 2.5 or 5 mg/d esaxerenone or placebo for 12 weeks. The primary end point was the change in urinary albumin-to-creatinine ratio from baseline to week 12 (with last observation carried forward).
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Results Esaxerenone treatment at 1.25 2.5 and 5 mg/d significantly reduced urinary albumin-to-creatinine ratio by the end of treatment (38% 50% and 56% respectively) compared with placebo (7%; 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.
