Question: In patients with type 2 diabetes mellitus, diabetic nephropathy, and hypertension, what effect does the angiotensin-II–receptor antagonist (ARA) irbesartan and the calcium-channel blocker amlodipine have on renal disease?
Design: Randomized (allocation concealed*), blinded (clinicians, patients, outcome assessors, and statisticians),* placebo-controlled trial with mean follow-up of 2.6 years (the Irbesartan Diabetic Nephropathy Trial [IDNT]).
Setting: 210 clinical centers worldwide.
Patients: 1715 patients between 30 and 70 years of age (mean age 59 y, 66% men) who had type 2 diabetes, hypertension, proteinuria defined as a urinary protein excretion rate ≥ 900 mg/24 hours, and serum creatinine levels between 88 and 265 µmol/L in women and between 106 and 265 µmol/L in men. Follow-up was 99%.
Intervention: Patients were allocated to irbesartan, titrated to 300 mg/d (n = 579); amlodipine, titrated to 10 mg/d (n = 567); or placebo (n = 569). Treatment targeted a systolic blood pressure ≤ 135 mm Hg and a diastolic blood pressure ≤ 85 mm Hg by using drugs other than angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers, and calcium-channel blockers, if necessary.†
Main outcome measures: The primary outcome was the composite of a doubling of the baseline serum creatinine level, onset of end-stage renal disease, or all-cause mortality. The secondary outcome was the composite of cardiovascular mortality, nonfatal myocardial infarction, heart failure resulting in hospitalization, neurologic deficit caused by a cerebrovascular event, or above-ankle lower-limb amputation.
Main results: Analysis was by intention to treat. After adjusting for mean blood pressure, irbesartan lowered the risk for the primary composite outcome more than did amlodipine (P = 0.005) or placebo (P = 0.03); this outcome did not differ for amlodipine and placebo (P = 0.47) (Table). The 3 groups did not differ for the secondary composite outcome.
Conclusion: In patients with type 2 diabetes, nephropathy, and hypertension, irbesartan was more effective in reducing progression of nephropathy independent of the effect on blood pressure than was amlodipine or placebo.
Irbesartan, amlodipine, or placebo for risk for a composite outcome in diabetic nephropathy and hypertension at mean 2.6 y‡
|Comparisons||Event rates||Adjusted RRR (95% CI)||NNT (CI)|
|Irbesartan vs amlodipine||33% vs 41%||24% (8 to 37)||12 (7 to 35)|
|Irbesartan vs placebo||33% vs 39%||19% (1 to 33)||16 (8 to 121)|
|Adjusted RRI (CI)||NNH|
|Amlodipine vs placebo||41% vs 39%||7% (−11 to 29)||Not significant|