Reno-protective effects of renin-angiotensin system blockade in type 2 diabetic patients: A systematic review and network meta-analysis

Abstract

Aims/hypothesis: This meta-analysis aimed to compare the renal outcomes between ACE inhibitor (ACEI)/angiotensin II receptor blocker (ARB) and other antihypertensive drugs or placebo in type 2 diabetes. Methods: Publications w ere identified from Medline and Embase up to July 2011. Only randomised controlled trials comparing ACEI/ARB monotherapy with other active drugs or placebo were eligible. The outcome of end-stage renal disease, doubling of serum creatinine, microvascular complications, microalbuminuria, macroalbuminuria and albuminuria regression were extracted. Risk ratios were pooled using a random-effects model if heterogeneity was present; a fixed-effects model was used in the absence of heterogeneity. Results: Of 673 studies identified, 28 were eligible (n=13-4,912). In direct meta-analysis, ACEI/ARB had significantly lower risk of serum creatinine doubling (pooled RR=0.66 [95% CI 0.52, 0.83]), macroalbuminuria (pooled RR=0.70 [95% CI 0.50, 1.00] ) and albuminuria regression (pooled RR 1.16 [95% CI 1.00, 1.39]) than other antihypertensive drugs, mainly calcium channel blockers (CCBs). Although the risks of end-stage renal disease and microalbuminuria were lower in the ACEI/ARB group (pooled RR 0.82 [95% CI 0.64, 1.05] and 0.84 [95% CI 0.61, 1.15], respectively), the differences were not statistically significant. The ACEI/ARB benefit over placebo was significant for all outcomes except microalbuminuria. A network meta-analysis detected significant treatment effects across all outcomes for both active drugs and placebo comparisons. Conclusions/interpretation: Our review suggests a consistent reno-protective effect of ACEI/ARB over other antihypertensive drugs, mainly CCBs, and placebo in type 2 diabetes. The lack of any differences in BP decrease between ACEI/ARB and active comparators suggest this benefit is not due simply to the antihypertensive effect. © 2011 The Author(s).