THE EFFECT OF ANGIOTENSIN-II RECEPTOR ANTAGONISM WITH LOSARTAN ON GLUCOSE-METABOLISM AND INSULIN SENSITIVITY

Objective To investigate the metabolic effects of losartan (Cozaar(R)) in patients with essential hypertension. Methods Twenty patients with mild hypertension (office blood pressure >140/95 mmHg and home diasto lic blood pressure >90 mmHg) were examined in a double-blind, placebo- controlled cross-over study of 4 weeks of treatment with 50-100 mg los artan. The effects on glucose metabolism were assessed by euglycaemic glucose clamp examinations [glucose disposal rate (GDR, mg/kg per min) ] and oral glucose-tolerance tests (OGTT). Results Supine blood pressu re was reduced from 146 +/- 3/ 90 +/- 3 mmHg on placebo to 134 +/- 4/8 3 +/- 3 mmHg on losartan and the difference was maintained during 120 min of insulin infusion and glucose clamping. GDR was 6.2 +/- 0.5 mg/k g per min on placebo and 6.4 +/- 0.5 mg/kg per min on losartan. The gl ucose and insulin responses (the area under the curve) during OGTT wer e similar with placebo and losartan (0.86 +/- 0.3 versus 0.88 +/- 0.4 and 341 +/- 60 versus 356 +/- 60, respectively; arbitary units). Serum cholesterol was 5.3 +/- 0.2 mmol/l on placebo and 5.1 +/- 0.2 mmol/l with losartan treatment. High-density lipoprotein cholesterol and trig lycerides were, respectively 1.1 +/- 0.1 and 1.5 +/- 0.2 mmol/l with p lacebo, and 1.1 +/- 0.1 and 1.4 +/- 0.1 mmol/l with losartan treatment . Conclusion In mildly hypertensive patients, selective angiotensin II receptor antagonism with losartan for 4 weeks lowers blood pressure a t rest and during 120 min of glucose clamping, and has neutral effects on insulin sensitivity, glucose metabolism and serum lipids.