Effect of Losartan on Microalbuminuria in Normotensive Patients with Type 2 Diabetes Mellitus

A Randomized Clinical Trial

15 July 2003 | Volume 139 Issue 2 | Pages 90-96

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.

Editors' Notes Context Angiotensin-receptor antagonists reduce renal and cardiovascular complications in patients with type 2 diabetes and hypertension. The effect of these drugs on normotensive patients with type 2 diabetes is not known. Contribution This 10-week randomized, placebo-controlled trial showed that in normotensive diabetic patients receiving losartan, albumin excretion rate was significantly reduced and blood pressure slightly decreased. Cautions The study included patients with systolic blood pressure up to 150 mm Hg and was too brief to evaluate progression of clinical renal disease. Angiotensin-receptor antagonists hold promise in preserving renal function in patients with type 2 diabetes without marked hypertension, but they warrant further study. –The Editors

 

Author and Article Information

From Ikazia Hospital and Erasmus University Medical Centre, Rotterdam, and University Hospital, Groningen, the Netherlands.

Acknowledgments: The authors thank Wouter Wijker and Ruurd Bennink for their help in statistical analyses, Rob Oosterom for advice on laboratory measurements, and Ron Leeneman of the virtual central laboratory.

Grant Support: By a grant from Merck, Sharp & Dohme, Haarlem, the Netherlands.

Potential Financial Conflicts of Interest:Consultancies: D. de Zeeuw (Bristol-Myers Squibb; Pfizer; Merck, Sharpe & Dohme; Yamanouchi Pharmaceutical Co.; Amgen).

Requests for Single Reprints: Adrienne A.M. Zandbergen, MD, Department of Internal Medicine, Ikazia Hospital, Montessoriweg 1, 3083 AN Rotterdam, the Netherlands; e-mail, adrienne_zandbergen{at}yahoo.com.

Current Author Addresses: Drs. Zandbergen, Baggen, and Ouwendijk: Department of Internal Medicine, Ikazia Hospital, Montessoriweg 1, 3083 AN Rotterdam, the Netherlands.

Drs. Lamberts and Bootsma: Department of Internal Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.

Dr. de Zeeuw: Department of Clinical Pharmacology, University Hospital Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.

Author Contributions: Conception and design: A.A.M. Zandbergen, M.G.A. Baggen, R.J.T. Ouwendijk.

Analysis and interpretation of the data: A.A.M. Zandbergen, M.G.A. Baggen, S.W.J. Lamberts, A.H. Bootsma, D. de Zeeuw, R.J.T. Ouwendijk.

Drafting of the article: A.A.M. Zandbergen.

Critical revision of the article for important intellectual content: M.G.A. Baggen, S.W.J. Lamberts, A.H. Bootsma, D. de Zeeuw, R.J.T. Ouwendijk.

Final approval of the article: A.A.M. Zandbergen, M.G.A. Baggen, S.W.J. Lamberts, A.H. Bootsma, D. de Zeeuw, R.J.T. Ouwendijk.

Provision of study materials or patients: A.A.M. Zandbergen, M.G.A. Baggen, A.H. Bootsma, R.J.T. Ouwendijk.

Statistical expertise: S.W.J. Lamberts, D. de Zeeuw.

Obtaining of funding: M.G.A. Baggen, R.J.T. Ouwendijk.

Administrative, technical, or logistic support: A.A.M. Zandbergen.

Collection and assembly of data: A.A.M. Zandbergen, M.G.A. Baggen, R.J.T. Ouwendijk.