ADVANCE: Breaking new ground in type 2 diabetes

John Chalmers, Vlado Perkovic, Rohina Joshi, Anushka Patel

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


OBJECTIVE AND RATIONALE: ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation) is a large-scale trial designed to investigate the benefits of blood pressure lowering and intensive glucose control in patients with type 2 diabetes, and to address a number of unresolved issues: whether blood pressure-lowering therapy and intensive glucose control therapy will reduce the risk of major vascular disease regardless of initial blood pressure or glucose concentration; whether more intensive glucose control targeting a haemoglobin A1c (HbA1c) level of 6.5% or less will confer greater protection against microvascular disease; and whether the benefits of the two interventions are additive. DESIGN AND METHODS: ADVANCE is a 2 x 2 factorial randomized clinical trial evaluating the risks and benefits of the low-dose fixed combination of perindopril and indapamide versus placebo to lower blood pressure and of an intensive gliclazide-MR-based glucose control regimen, targeting an HbA1c of 6.5% or less versus standard guidelines based therapy for glucose control. There are two primary outcomes: a composite macrovascular endpoint and a composite microvascular endpoint. RESULTS: A total of 12 878 participants from 215 centres in 20 countries entered a 6-week run-in phase between June 2001 and January 2003, and 11 140 patients were randomly assigned by March 2003. The average (SD) systolic and diastolic blood pressure fell from 145 (22)/81 (11) to 137 (20)/78 (10) mmHg during the 6-week run-in phase, during which participants received one tablet of open-labelled perindopril 2 mg/indapamide 0.625 mg. Of the 12 878 patients who entered the run-in, only 3.6% withdrew because of suspected intolerance to perindopril/indapamide. The study is half way through follow-up and both the study medications (perindopril 2 mg/indapamide 0.625 mg and gliclazide-MR) continue to be well tolerated. Completion is expected in 2007. CONCLUSION: Safe and effective blood pressure lowering with the fixed low-dose combination of perindopril and indapamide was confirmed during the run-in phase in 11 140 patients with type 2 diabetes, who were subsequently randomly assigned. Post-randomization study treatments have been well tolerated, and the completion of follow-up is scheduled in 2007.

Original languageEnglish
Pages (from-to)S22-S28
Number of pages7
JournalJournal of Hypertension
Issue numberSUPPL. 5
Publication statusPublished - Aug 2006
Externally publishedYes


  • Blood pressure lowering
  • Diamicron-MR
  • Intensive glucose control
  • Macrovascular disease
  • Microvascular disease
  • Perindoprilindapamide combination
  • Type 2 diabetes


Dive into the research topics of 'ADVANCE: Breaking new ground in type 2 diabetes'. Together they form a unique fingerprint.

Cite this