Combination blood pressure lowering therapy in patients with type 2 diabetes: messages from the ADVANCE trial

The Action in Diabetes and Vascular disease: preterAx and diamicroN Controlled Evaluation (ADVANCE) trial investigated the effects of intensive blood pressure (BP) lowering using a fixed combination of perindopril-indapamide versus placebo in type 2 diabetes (T2D). The study showed that combination perindopril-indapamide had significant benefits in reducing cardiovascular, renal, and mortality events, with consistent relative risk reductions across different patient subgroups. Secondary analyses of ADVANCE have identified novel risk markers in T2D including cessation of BP lowering therapy, absent peripheral pulses and cardiac biomarkers to name a few. ADVANCE also shed light on practical aspects of hypertension management, including the limitations of office BP, tolerability of combination BP lowering therapy across the range of BP levels and the interpretation of changes in serum creatinine after treatment initiation. This review article summarizes the findings of ADVANCE and its subsequent substudies, which have been foundational in our understanding of BP management and the use of combination BP lowering therapy in T2D.