A single-masked study comparing doxazosin and enalapril in patients with non—insulin-dependent diabetes mellitus and hypertension

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are recognized as eminently suitable drugs for the treatment of hypertensive patients with non—insulin-dependent diabetes mellitus (NIDDM). They are metabolically neutral, may reduce insulin resistance, and are reno-protective. Long-acting alpha 1-blockers such as doxazosin are also metabolically neutral, effective antihypertensive agents. The objective of this study was to compare the efficacy and acceptability of doxazosin and the ACE inhibitor enalapril. We investigated the effects of these drugs on blood pressure, diabetic control, lipid levels, renal function, and safety in patients with NIDDM (type II diabetes) and mild-to-moderate hypertension. Fifty-two patients with NIDDM and stable essential hypertension were randomized to two parallel groups. The study comprised three phases: placebo washout (4 weeks), dose adjustment monotherapy of doxazosin 1 to 4 mg/d or enalapril 5 to 20 mg/d (8 weeks), and maintenance (4 weeks). Patients not controlled on monotherapy entered a 4-week, open-label, dual-therapy phase before maintenance. Black patients were excluded, as were those with macroalbuminuria (urinary albumin >3.5 g/24 h) and renal failure (serum creatinine ⩾150 μmol/L). Variables being compared included critical blood pressure (CBP) (ie, the lesser of mean sitting and standing diastolic blood pressure [DBP]), sitting and standing systolic blood pressure (SBP) and DBP, blood glucose (fasting and postprandial), serum cholesterol levels, serum triglyceride levels, body mass index (BMI), and electrocardiographic (ECG) evidence of left ventricular hypertrophy. Patients in the doxazosin group exhibited a larger decrease in CBP (−11.3 vs −6.2 mm Hg), sitting (−9.9 vs −1.1) and standing SBP (−10.3 vs 0.0), and sitting (−12.2 vs −8.4) and standing DBP (−7.9 vs −0.8) compared with the enalapril group. The difference in the reduction in standing DBP was statistically significant, whereas the other differences did not reach statistical significance. No statistically significant differences were found between the groups in metabolic variables, BMI, or ECG findings. The metabolic profiles of enalapril and doxazosin were similar, except for a mild increase in serum triglyceride levels in the doxazosin group. However, the confidence index for the doxazosin-enalapril difference was wide, meaning that no conclusive statement can be made about the difference. Adverse events were common (26.9% doxazosin vs 42.3% enalapril), but none were serious. The doxazosin-treated patients showed a larger decrease in blood pressure on average than patients receiving enalapril; apart from standing DBP, the differences were not statistically significant. This study has demonstrated that doxazosin is at least as affective as enalapril in decreasing blood pressure in patients with NIDDM and mild-to-moderate hypertension.