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Evidence summaries

Intensive Glucose Lowering in Type 2 Diabetes

Intensive glucose lowering by means of combining several drugs including insulin may prevent some cardiovascular events, but it may even increase mortality. Level of evidence: "C"

An RCT 1 including a total of 10251 patients (mean age 62.2 years) with a median glycated hemoglobin level of 8.1% compared intensive therapy (targeting a HbA1c below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). 35% of the patients had a previous cardiovascular event. During 3.5 years of follow up, the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes occurred in 352 patients in the intensive therapy group and in 371 patients in the standard therapy group (HR 0.90, 95% CI 0.78 to 1.04). 257 patients in the intensive therapy group and 203 patients in the standard therapy group died (HR 1.22, 95% CI 1.91 to 1.46). Hypoglycemia needing assistance and weight gain of more than 10 kg were more frequent in the intensive therapy group.

An RCT 2 including 11140 patients with type 2 diabetes compared intensive glucose control defined as the use of gliclazide plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. After a median of 5 years of follow- up, the mean glycated hemoglobin level was lower in the intensive control group (6.5%) than in the standard control group (7.3%). The primary composite endpoint of major macrovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular event was reached by 18.1% of the patients in the intensive control group and 20.0% in the standard control group (HR 0.90, 95% CI 0.82 to 0.98), mainly because of a relative 21% reduction in nephropathy. Death from any cause did not differ (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28).

Comment: The quality of evidence is downgraded by inconsistency of results and by heterogeneity of interventions (differing use of insulin in the trials).

References

  • The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-2559.
  • The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-2572.

Primary/Secondary Keywords