The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity

Abstract

Objective 

To investigate the metabolic effects of losartan (Cozaar®) in patients with essential hypertension.

Methods 

Twenty patients with mild hypertension (office blood pressure>140/95 mmHg and home diastolic blood pressure>90 mmHg) were examined in a double-blind, placebo-controlled cross-over study of 4 weeks of treatment with 50-100 mg losartan. 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 pressure was reduced from 146 + 3/90 ± 3 mmHg on placebo to 134 ±4/83 ± 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/kg per min on placebo and 6.4 ± 0.5 mg/kg per min on losartan. The glucose and insulin responses (the area under the curve) during OGTT were 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 triglycerides were, respectively, 1.1 ± 0.1 and 1.5 ± 0.2 mmol/l with placebo, 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 at rest and during 120 min of glucose clamping, and has neutral effects on insulin sensitivity, glucose metabolism and serum lipids.