Effect of the mineralocorticoid receptor antagonist eplerenone on liver fat and metabolism in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial (MIRAD trial)

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Marie L. Johansen, Morten Schou, Patrick Rossignol, Maria R. Holm, Jon Rasmussen, Niels Brandt, Mikkel Frandsen, Elizaveta Chabanova, Flemming Dela, Jens Faber, Caroline Kistorp

Aim To investigate whether the mineralocorticoid receptor antagonist eplerenone has beneficial effects on liver fat and metabolism in patients with type 2 diabetes (T2D), the mineralocorticoid receptor antagonist in type 2 diabetes (MIRAD) trial. Material and methods In this 26-week, double-blind, randomized, placebo-controlled trial, we enrolled 140 patients with T2D and high risk of cardiovascular disease. Patients were randomized 1:1 to either eplerenone with a target dose of 200 mg/day for patients with estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m(2) or more and 100 mg/day for patients with eGFR between 41 and 59 mL/min per 1.73 m(2) or placebo. The primary outcome measure was change in liver fat by proton magnetic resonance spectroscopy at week 26 from baseline; secondary outcomes were changes in metabolism, and safety by incident hyperkalaemia. Results No changes in liver fat in the eplerenone group 0.91% (95% CI -0.57 to 2.39) or the placebo group -1.01% (-2.23 to 0.21) were found. The estimated absolute treatment difference was 1.92% (-3.81 to 0.01; P = 0.049). There was no beneficial impact on supporting secondary outcome variables of metabolism as fat mass distribution, lipid metabolism or insulin resistance. Despite a high dosage of eplerenone 164 versus 175 mg in patients treated with placebo (P = 0.228), the number of patients with incident hyperkalaemia (>= 5.5 mmol/L) was low, with six in the eplerenone versus two in the placebo group (P = 0.276). Conclusion The addition of high doses of eplerenone to background antidiabetic and antihypertensive therapy does not show beneficial effects on liver fat and metabolism in patients with T2D.
Original languageEnglish
JournalDiabetes, Obesity and Metabolism
ISSN1462-8902
DOIs
Publication statusE-pub ahead of print - 2019

    Research areas

  • eplerenone, hyperkalaemia, liver fat, mineralocorticoid receptor antagonist

ID: 224021515