Abstract

Objective- To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long standing type 2 diabetes.

Research Design And Methods- Multi-centre, factorial randomized trial of perindopril-indapamide versus placebo (double blind comparison), and intensive glucose control with a gliclazide MR-based regimen (target hemoglobin A1c≤6.5%) versus standard glucose control (open comparison) in 11,140 participants with type 2 diabetes who participated in the ADVANCE trial. Annual event rates and risks of major macrovascular and microvascular events considered jointly and separately, renal events and death during an average 4.3-years of follow-up were assessed, using Cox proportional hazards models.

Results- There was no interaction between the effects of the routine blood pressure lowering and intensive glucose control for any of the pre-specified clinical outcomes (all p>0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. When compared to neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% confidence interval [CI 12-50%, p=0.005), new onset macroalbuminuria by 54% (CI 35-68%, p<0.0001) and new onset microalbuminuria by 26% (CI 17-34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (CI 1-32%, p=0.04).

Conclusions- The effects of routine blood pressure lowering and intensive glucose control were independent of one another and when combined produced additional reductions in clinically relevant outcomes.