An association exists between
hyperaldosteronism,
hypertension and impaired
insulin action.
Eplerenone is a selective
mineralocorticoid receptor antagonist; however, little is known about its effects on
insulin action. The aim of this study was to determine the effect of
eplerenone on
insulin action in hypertensive adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled, double-blind, crossover design was employed. After a 6-week washout period, hypertensive, non-diabetic patients were treated with either
eplerenone 25 mg twice daily or
doxazosin 2 mg twice daily for 12 weeks. After each treatment period,
insulin action was assessed by a hyperinsulinaemic euglycaemic clamp, with
isotope dilution methodology. After washout, treatment groups were crossed over. Fifteen patients completed the study. There were no differences in fasting
glucose, or fasting
insulin between treatment with
eplerenone or
doxazosin. The measure of overall
insulin sensitivity, exogenous
glucose infusion rates during the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) μmol kg(-1) min(-1) after
eplerenone and 23.3 (3.6) μmol kg(-1) min(-1) after
doxazosin (P=0.83). Isotopically determined fasting endogenous
glucose production rates were similar after both treatments (
eplerenone 9.4 (0.6) μmol kg(-1) min(-1) vs
doxazosin 10.6 (0.7) μmol kg(-1) min(-1)). There was a trend for lower endogenous
glucose production rates during hyperinsulinaemia following
eplerenone compared with
doxazosin (2.0 (0.8) μmol kg(-1) min(-1) vs 4.1 (0.9) μmol kg(-1) min(-1)). There was no difference in
insulin stimulated peripheral
glucose utilisation rates
after treatment with
eplerenone or
doxazosin (25.4 (3.6) μmol kg(-1) min(-1) vs 27.0 (3.9) μmol kg(-1) min(-1)). This study gives reassuring evidence of the neutral effect of
eplerenone on
insulin action in hypertensive, non-diabetic patients.