Does Glycemic Control Offer Similar Benefits Among Patients With Diabetes in Different Regions of the World?

Results from the ADVANCE trial

  1. John Chalmers, MD, PHD1
  1. 1The George Institute, University of Sydney, Sydney, Australia
  2. 2Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
  3. 3School of Public Health, Monash University, Australia
  4. 4Chinese Hypertension League Institute, Beijing, China
  5. 5Chinese People’s Liberation Army General Hospital, Beijing, China
  6. 6Imperial College, London, U.K.
  7. 7Institute of Cardiology, Warsaw, Poland
  8. 8All India Institute of Medical Sciences, Delhi, India
  9. 9Government Medical College, Nagpur, India
  10. 10Sheffield Northern Hospital, Sheffield, U.K.
  1. Corresponding author: Mark Woodward, mwoodward{at}


OBJECTIVE Participants in ADVANCE were drawn from many countries. We examined whether the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia, established market economies (EMEs), and eastern Europe.

RESEARCH DESIGN AND METHODS ADVANCE was a clinical trial of 11,140 patients with type 2 diabetes, lasting a median of 5 years. Demographic and clinical characteristics were compared across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified release–based intensive glucose control regimen, targeting an HbAlc of ≤6.5%, were compared across regions using Cox proportional hazards models.

RESULTS When differences in baseline variables were allowed for, the risks of primary outcomes (major macrovascular or microvascular disease) were highest in Asia (joint hazard ratio 1.33 [95% CI 1.17–1.50]), whereas macrovascular disease was more common (1.19 [1.00–1.42]) and microvascular disease less common (0.77 [0.62–0.94]) in eastern Europe than in EMEs. Risks of death and cardiovascular death were highest in eastern Europe, and the mean difference in glycosylated hemoglobin between the intensive and standard groups was lowest in EMEs. Despite these and other differences, the effects of intensive glycemic control were not significantly different (P ≥ 0.23) between regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes.

CONCLUSIONS Irrespective of absolute risk, the effects of intensive glycemic control with the gliclazide MR-based regimen used in ADVANCE were similar across Asia, EMEs, and eastern Europe. This regimen can safely be recommended for patients with type 2 diabetes in all of these regions.


  • Received April 21, 2011.
  • Accepted August 28, 2011.

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  1. Diabetes Care vol. 34 no. 12 2491-2495
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