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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)
Author(s) -
Johansen Marie L.,
Schou Morten,
Rossignol Patrick,
Holm Maria R.,
Rasmussen Jon,
Brandt Niels,
Frandsen Mikkel,
Chabanova Elizaveta,
Dela Flemming,
Faber Jens,
Kistorp Caroline
Publication year - 2019
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13809
Subject(s) - eplerenone , medicine , mineralocorticoid receptor , placebo , endocrinology , spironolactone , type 2 diabetes , gastroenterology , diabetes mellitus , aldosterone , pathology , alternative medicine
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.