EFFECTS OF COMBINATION THERAPY WITH AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR AND THIAZIDE DIURETIC ON INSULIN ACTION IN ESSENTIAL-HYPERTENSION

Objective To determine whether combination of an angiotensin convertin g enzyme inhibitor with a high dose of thiazide diuretic avoids advers e metabolic consequences of thiazide diuretics. Design Double-blind ra ndomized crossover study of two 12-week treatment periods with captopr il (up to 100 mg/day) either alone or in combination with 5 mg bendrof luazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period. Setting Outpatient clinics in greater Belfast. Patients Fifteen white non-diabetic essent ial hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast. Main outcome measures Systolic and diast olic blood pressures and peripheral and hepatic insulin action. Result s Two patients failed to complete the study. Blood pressure was lowere d (139/89 +/- 18/7 mmHg combination versus 160/97 +/- 21/7 mmHg captop ril; P < 0.001). Fasting insulin level was raised (7.9 +/- 3.6 mU/l co mbination versus 6.2 +/- 3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and tri glyceride levels. Serum potassium level was lowered (3.8 +/- 0.4 mmol/ l combination versus 4.2 +/- 0.4 mmol/l captopril, P < 0.05). Postabso rptive endogenous glucose production was raised (10.8 +/- 1.7 mu mol/k g per min combination versus 10.0 +/- 1.5 mu mol/kg per min captopril; P < 0.01) and was greater than baseline (9.7 +/- 2.1 mu mol/kg per mi n, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to ma intain euglycaemia did not differ (32.4 +/- 7.6 mu mol/kg per min capt opril, 32.7 +/- 6.2 mu mol/kg per min combination, 31.5 +/- 7.2 mu mol /kg per min baseline). Conclusions Combination therapy increased gluco se production (compared with captopril alone), indicating hepatic insu lin resistance. It cannot be assumed that combined preparations with a ngiotensin converting enzyme inhibitors will ameliorate adverse effect s of high doses of thiazide diuretics on insulin action. (C) Rapid Sci ence Ltd.