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Angiotensin-Receptor Antagonists for Diabetic Nephropathy

Angiotensin-converting–enzyme (ACE) inhibitors are used widely as renoprotective agents in diabetic patients. Now, in 3 international, industry-sponsored, randomized trials, investigators examine the effects of a different class of drugs -- angiotensin-receptor antagonists -- on nephropathy caused by type 2 diabetes.

In the first study, 1715 patients with type 2 diabetes, blood pressure higher than 135/85 mm Hg, serum creatinine between 1 and 3 mg/dL, and urinary protein excretion at least 900 mg/day received either irbesartan, amlodipine, or placebo; other antihypertensives were permitted if necessary. During an average follow-up of 2.6 years, a primary composite outcome (doubling of serum creatinine, end-stage renal disease, or death from any cause) occurred in significantly fewer patients who received irbesartan than in patients who received amlodipine or placebo (33 percent vs. 41 percent or 39 percent).

In a second study, investigators used the same composite endpoint in a comparison between losartan and placebo in 1513 patients; enrollment criteria were similar to those in the first study. After an average 3.4 years of treatment, the endpoint was reached significantly less often with losartan than with placebo (15.9 vs. 18.1 events per 100 patient-years).

A third study included 590 patients with type 2 diabetes and less advanced nephropathy (serum creatinine, 1.5 mg/dL for men and 1.1 mg/dL for women; albumin excretion rate, 20 to 200 µg/min). The patients received irbesartan (150 or 300 mg daily) or placebo. During 2 years of follow-up, progression of albuminuria occurred significantly less often in the 300-mg-irbesartan group than in the placebo group (5.2 percent vs. 14.9 percent). The frequency in the 150-mg-irbesartan group was 9.7 percent.

Comment: These results show that angiotensin-receptor antagonists are beneficial in patients with type 2 diabetes and early or established nephropathy. In each trial, analyses suggested that the benefit was independent of blood pressure lowering. Unfortunately, diabetic nephropathy progresses in many patients despite use of these drugs. Finally, an editorialist criticizes the fact that these investigators did not compare ACE inhibitors with receptor antagonists, because ACE inhibitors likely will be less expensive than receptor antagonists in the foreseeable future.

— AS Brett

Published in Journal Watch General Medicine September 28, 2001

Citation(s):

Lewis EJ et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001 Sep 20 345 851-860.

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Brenner BM et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001 Sep 20 345 861-869.

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Parving H-H et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001 Sep 20 345 870-878.

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Hostetter TH. Prevention of end-stage renal disease due to type 2 diabetes. N Engl J Med 2001 Sep 20 345 910-912.

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