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.

Albuminuria/complications/*drug therapy/physiopathology, Blood Pressure/drug effects, Creatinine/metabolism, Diabetes Mellitus, Type 2/*complications/urine, Double-Blind Method, Female, Humans, Losartan/administration & dosage/adverse effects/*therapeutic use, Male, Middle aged, Multivariate Analysis, Patient Compliance, Receptors, Angiotensin/*antagonists & inhibitors, Research Support, Non-U.S. Gov't
Annals of Internal Medicine
Erasmus MC: University Medical Center Rotterdam

Zandbergen, A.A.M, Baggen, M.G.A, Lamberts, S.W.J, Bootsma, A.H, de Zeeuw, D, & Ouwendijk, R.J.T. (2003). Effect of losartan on microalbuminuria in normotensive patients with type 2 diabetes mellitus. A randomized clinical trial. Annals of Internal Medicine. Retrieved from