Effect of dual blockade of the renin-angiotensin system on the progression of type 2 diabetic nephropathy: a randomized trial.

Background: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers has been shown to lessen the rate of decrease in glomerular filtration rate in patients with diabetic nephropathy.

Study Design: A multicenter open-label randomized controlled trial to compare the efficacy of combining the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor blocker irbesartan with that of each drug in monotherapy (at both high and equipotent doses) in slowing the progression of type 2 diabetic nephropathy.

Setting & Population: 133 patients with type 2 diabetic nephropathy (age, 66 ± 8 years; 76% men) from 17 centers in Spain.

Intervention: Patients were randomly assigned (1:1:2) to lisinopril (n = 35), irbesartan (n = 28), or the combination of both (n = 70).

Outcomes: The primary composite outcome was a >50% increase in baseline serum creatinine level, end-stage renal disease, or death.

Results: Baseline values for mean estimated glomerular filtration rate and blood pressure were 49 ± 21 mL/min/1.73 m(2) and 153 ± 19/81 ± 11 mm Hg. Mean geometric baseline proteinuria was protein excretion of 1.32 (95% CI, 1.10-1.62) g/g creatinine. After a median follow-up of 32 months, 21 (30%) patients in the combination group, 10 (29%) in the lisinopril group, and 8 (29%) in the irbesartan group reached the primary outcome. HRs were 0.96 (95% CI, 0.44-2.05; P = 0.9) and 0.90 (95% CI, 0.39-2.02; P = 0.8) for the combination versus the lisinopril and irbesartan groups, respectively. There were no significant differences in proteinuria reduction or blood pressure control between groups. The number of adverse events, including hyperkalemia, was similar in all 3 groups.

Limitations: The study was not double blind. The sample size studied was small.

Conclusions: We were unable to show a benefit of the combination of lisinopril and irbesartan compared to either agent alone at optimal high doses on the risk of progression of type 2 diabetic nephropathy.