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). Issue 10 (5th July 2019)

• Record Type: Journal Article
• Authors: Johansen, Marie L.; Schou, Morten; Rossignol, Patrick; Holm, Maria R.; Rasmussen, Jon; Brandt, Niels; Frandsen, Mikkel; Chabanova, Elizaveta; Dela, Flemming; Faber, Jens; Kistorp, Caroline
• Is Part Of: Diabetes, obesity & metabolism. Volume 21:Issue 10(2019)
• Page Start: 2305
• Page End: 2314
• Publication Date: 2019-07-05
• Subjects: eplerenone -- hyperkalaemia -- liver fat -- mineralocorticoid receptor antagonist; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13809
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: 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.