Does Tight Glycemic Control Prevent Cardiovascular Events in Type 2 Diabetic Patients?

Contrary to popular belief, evidence that intensive glucose-lowering therapy improves macrovascular outcomes in patients with type 2 diabetes is limited. In two new randomized trials, researchers address this issue.

The NIH-sponsored ACCORD study involved 10,251 type 2 diabetic patients (mean age, 62; median glycosylated hemoglobin [HbA_1c], 8.1%) with known cardiovascular disease or at least two additional risk factors. Patients received either intensive therapy (target HbA_1c, 6%, with antidiabetic regimens individualized by clinicians) or standard therapy (target HbA_1c, 7%–7.9%). Although glycemic control was significantly better with intensive treatment than with standard treatment throughout the trial (median HbA_1c, 6.4% vs. 7.5%), the trial was stopped after an average follow-up of 3.5 years, because mortality was higher in the intensive-treatment group than in the standard-treatment group (5% vs. 4%; P=0.04). Moreover, the groups did not differ significantly in the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (6.9% vs. 7.2%). Severe hypoglycemia and weight gain were more common in the intensive treatment group, but the factors mediating the higher mortality with intensive treatment were unclear.

The second study — the ADVANCE trial — involved 11,140 patients (mean age, 66; median HbA_1c, 7.2%). The intensively treated group received the sulfonylurea gliclazide as initial therapy (with other drugs added as required to reach target HbA_1c of 6.5%), and the standard-treatment group received any drugs except gliclazide (with no specified target HbA_1c). Although HbA_1c averaged 6.5% with intensive treatment and 7.3% with standard treatment during 5 years of follow-up, no significant difference was noted between groups for the primary endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (10.0% vs. 10.6%) or for all-cause mortality. The microvascular outcome of new or worsening nephropathy occurred significantly less often in the intensive-treatment group (4.1% vs. 5.2%), but severe hypoglycemia was more common with intensive treatment. This study was supported by the maker of gliclazide.