Effect of losartan on microalbuminuria in normotensive patients with type 2 diabetes mellitus. A randomized clinical trial

BACKGROUND: Angiotensin-converting enzyme inhibitors have shown antiproteinuric effects in normotensive and hypertensive diabetic patients. Angiotensin-receptor antagonists reduce urinary albumin excretion and the risk for renal and cardiovascular complications in hypertensive patients with type 2 diabetes mellitus. The effect of angiotensin-receptor antagonists in normotensive diabetic patients with microalbuminuria has not yet been reported. OBJECTIVE: To assess the antiproteinuric effects of losartan in normotensive patients with type 2 diabetes and microalbuminuria. DESIGN: Multicenter randomized, double-blind, placebo-controlled clinical trial. SETTING: 19 outpatient clinics in the Netherlands. PATIENTS: 147 normotensive patients with type 2 diabetes mellitus and microalbuminuria. INTERVENTION: 74 patients were randomly assigned to receive losartan and 73 patients were assigned to receive placebo for 10 weeks; 71 patients in each group completed the study. The losartan dose was 50 mg during the first 5 weeks and 100 mg during the subsequent 5 weeks. MEASUREMENTS: Change in urinary albumin excretion rate after 5 and 10 weeks, change in creatinine clearance and blood pressure, and safety and tolerability of losartan. RESULTS: A significant 25% relative reduction in the albumin excretion rate occurred after 5 weeks of the 50-mg losartan dose, with further improvement over the subsequent 5 weeks with the 100-mg dose (relative reduction, 34%). In the losartan group, creatinine clearance did not improve and blood pressure decreased slightly. Side effects did not differ between treatment groups. CONCLUSIONS: The angiotensin-receptor antagonist losartan reduces urinary albumin excretion in normotensive patients with type 2 diabetes and microalbuminuria. In multivariate analysis, the antiproteinuric effect of losartan was independent of the associated reduction in blood pressure. Losartan was safe and well tolerated in these normotensive patients.