New insights from ADVANCE

J Hypertens Suppl. 2007 Jun;25(1):S23-30. doi: 10.1097/01.hjh.0000271506.69949.46.


Objectives: ADVANCE (Action in Diabetes and Vascular Disease - PreterAx and DiamicroN MR Controlled Evaluation) is a large-scale clinical trial designed to investigate the benefits of blood pressure lowering and intensive glucose control in patients with type 2 diabetes mellitus.

Methods and participants: ADVANCE is a 2 x 2 factorial randomized trial evaluating the benefits of the low-dose fixed combination of perindopril and indapamide versus placebo to lower blood pressure and of an intensive gliclazide-MR-based regimen, targeting glycosylated haemoglobin (HbA1c) levels of 6.5% or less versus standard therapy to lower blood glucose. The two primary outcomes, taken separately and jointly, are a composite macrovascular endpoint and a composite microvascular endpoint.

Results: A total of 11 140 participants were randomized between July 2001 and March 2003 from among 12 878 individuals with type 2 diabetes recruited from 215 centres in 20 countries, who entered a 6-week run-in phase. The average (SD) baseline blood pressure of 145(22)/81 (11) mmHg fell by 8/3 mmHg during the run-in phase during which participants received one tablet of open-labelled perindopril 2 mg-indapamide 0.625 mg. Only 3.6% of the 12 878 patients who entered the run-in phase withdrew because of suspected intolerance to perindopril-indapamide. With over 4 years of follow-up on average so far, over 80% of participants are still adhering to randomized therapy. Follow-up of the blood pressure arm will be completed during 2007.

Conclusion: The safety and efficacy of perindopril-indapamide in lowering blood pressure and of a gliclazide-MR-based regimen in lowering blood glucose have been established with the completion of a 6-week run-in phase and of more than 4 years of post-randomization follow-up. It is anticipated that ADVANCE will provide many new insights including: whether blood pressure lowering with perindopril-indapamide reduces the risk of both macrovascular and microvascular events irrespective of baseline blood pressure; whether more intensive blood pressure lowering with a gliclazide-MR-based regimen targeting on HbA1c levels of 6.5% or less reduces these two outcomes compared with standard guidelines therapy; and finally whether the separate benefits of these two treatment regimens are additive.

Publication types

  • Review

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Therapy, Combination
  • Gliclazide / therapeutic use*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Hypertension / physiopathology
  • Hypoglycemic Agents / therapeutic use*
  • Indapamide / therapeutic use
  • Internationality
  • Middle Aged
  • Multicenter Studies as Topic
  • Perindopril / therapeutic use
  • Randomized Controlled Trials as Topic


  • Antihypertensive Agents
  • Blood Glucose
  • Drug Combinations
  • Hypoglycemic Agents
  • Indapamide
  • Gliclazide
  • Perindopril