High-dose eplerenone as an add-on treatment may decrease urinary albumin-to-creatinine ratio (UACR) in patients with type 2 diabetes who have or are at high risk for cardiovascular disease (CVD) and do not have impaired kidney function, according to investigators.

In the MIRAD trial (Mineralocorticoid Receptor Antagonist in Type 2 Diabetes), Caroline Kistorp, PhD, of Copenhagen University Hospital in Copenhagen, Denmark, and colleagues randomly assigned 140 patients to either high-dose (100-200 mg)  eplerenone or a dose-matched placebo as an add-on to background antihypertensive treatment for 26 weeks. No changes in renin-angiotensin system inhibitors were allowed.

At baseline, albuminuria was present in 31% of patients, of whom 5% had a UACR of more than 300 mg/g. Over 26 weeks, UACR significantly decreased by 34% in the eplerenone group compared with the placebo group from a baseline mean of 17 mg/g (P =.005), Dr Kistorp’s team reported in Diabetes & Metabolism. No significant decrease in 24-hour ambulatory blood pressure occurred.

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With respect to safety, the investigators found no significant differences in mild hyperkalemia (serum potassium 5.5 mmol/L or higher) between groups (6 eplerenone vs 2 placebo recipients; P =.276) and no severe hyperkalemia (6.0 mmol/L or higher). Certain patients were excluded from the trial, including those with an estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or less, heart failure with reduced left ventricular ejection fraction, baseline serum potassium of 5.0 mmol/L or higher, or severe liver disease

Eplerenone use was associated with only a minor increase in serum potassium of 0.26 mmol/L and a decrease in eGFR of 3.5 mL/min/1.73 m2 at week 26. All patients who experienced hyperkalemia or increased serum creatinine returned to safe levels of serum potassium with drug dose reductions. Notably, only 12 patients had an eGFR of 41 to 59 mL/min/1.73 m2 and, per protocol, they could receive a maximum dose of only 100 mg eplerenone. Of all patients, 30% did not reach the 200 mg target dose of eplerenone.

The researchers cautioned against applying these trial results to patients with impaired kidney function.

“This shows that the addition of eplerenone, even at high doses, is manageable in a contemporary clinical setting in [type 2 diabetes] patients with normal kidney function with adequate control,” Dr Kistorp’s team stated. “However, an increase in serum potassium is apparently unavoidable, so risk management could benefit from the addition of a potassium-binding agent to counteract hyperkalemia.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Brandt-Jacobsen NH, Johansen ML, Rasmussen J, et al. Effect of high-dose mineralocorticoid receptor antagonist eplerenone on urinary albumin excretion in patients with type 2 diabetes and high cardiovascular risk: Data from the MIRAD trial. Published online September 9, 2020. Diabetes Metab. doi:10.1016/j.diabet.2020.08.005