A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients

Abstract

This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 ± 0.32 (mean ± SEM) to 3.97 ± 0.31 mg/kg/min ( P = .02). A similar tendency was observed with enalapril: from 3.59 ± 0.32 to 3.94 ± 0.30 mg/kg/min ( P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 ± 0.11 to 1.39 ± 0.13 with amlodipine ( P = .03) and from 1.25 ± 0.13 to 1.49 ± 0.16 with enalapril ( P = .01). LDL cholesterol decreased with amlodipine (mean change, −11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.