Action in Diabetes and Vascular Disease - ADVANCE DM


The goal of the trial was to evaluate blood pressure lowering and intensive glucose control for the prevention of vascular disease among high-risk patients with type 2 diabetes; the present summary describes the results of the glycemic control intervention.

Study Design

Patient Populations:

  • Type 2 diabetes
  • Age 55 years or older
  • Elevated risk of vascular disease defined as ≥1 of the following: age ≥65 years, history of major macrovascular or microvascular disease, first diagnosis of diabetes >10 years prior to entry, and other major risk factors

    Patients Enrolled: 11,140
    Mean Follow Up: 4.3 years, 9.9 years
    Mean Patient Age: 66 years
    Female: 43%

Primary Endpoints:

  • Major vascular events defined as a composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or new or worsening nephropathy or retinopathy

Drug/Procedures Used:

Patients were randomized to a gliclazide-based intensive glucose control (glycated hemoglobin <6.5%) or standard glucose control (based on local guidelines).

Principal Findings:

Mean glycated hemoglobin was 7.5% in both groups. The between-group difference in glycated hemoglobin levels (0.67%, p < 0.001) was no longer evident at the first post-trial visit. Approximately two-thirds of patients had a history of hypertension, and 75% were already on blood pressure lowering therapy.

All-cause mortality was similar in the intensive glucose control group versus the standard glucose control group (8.9% vs. 9.6%, p = 0.28).

- Major macrovascular events: 10.0% vs. 10.6% (p = 0.32), respectively
- Major microvascular events: 3.8% vs. 4.4% (p = 0.11), respectively

All-cause mortality as well as major macrovascular and major microvascular events remained similar between treatment groups in long-term follow-up.


Among high-risk patients with type 2 diabetes, use of a blood pressure intervention program with the combination of perindopril and indapamide was associated with a significant reduction in death and vascular events compared with placebo through a mean follow-up of 4.3 years. Benefit persisted late into follow-up, which suggests a memory effect (or carry forward) from active control of blood pressure among type 2 diabetics (see ADVANCE BP trial). However, intensive glycemic control was not associated with a reduction in macrovascular or microvascular events.


Zoungas S, Chalmers J, Neal B, et al., on behalf of the ADVANCE-ON Collaborative Group. Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes. N Engl J Med 2014;Sep 19:[Epub ahead of print].

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