Near-Normalization of Glucose and Microvascular Diabetes Complications: Data from ACCORD and ADVANCE.

OBJECTIVE: To compare results of clinical trials that assessed the impact of near-normalization of glucose on microvascular complications in type 2 diabetes.

METHODS: ACCORD (N = 10,234) and ADVANCE (N = 11,140) tested the hypothesis that near-normalization of glucose reduces microvascular complications in adults with established type 2 diabetes. Differences in incidence rates (intensive versus standard glucose control) for specific microvascular complications are expressed as 'number needed to treat' (NNT) to prevent one microvascular complication. The impact of blood pressure (BP) control and fenofibrate use on microvascular complications was also assessed.

RESULTS: In ADVANCE, near-normalization of glucose reduced new or worsening nephropathy (NNT = 77 for 5 years to prevent one occurrence), but not eye or foot complications. In ACCORD, near-normalization of glucose did not reduce prespecified composite measures of advanced microvascular complications, and impact on secondary microvascular outcomes was mixed. The ancillary ACCORD Eye Study found reduced progression in retinopathy with near-normalization of glucose (NNT = 32 for 4 years), and with blinded fenofibrate therapy (NNT = 27 for 4 years), but neither intervention reduced vision loss. ADVANCE showed a benefit of intensive BP control (mean BP 133/70 mmHg) on microvascular complications, independent of glucose control.

CONCLUSIONS: End-stage microvascular complications were not altered by near-normalization of glucose. Some early manifestations of microvascular complications were reduced, with inconsistencies across studies in which were affected. These early and inconsistent micro-vascular effects must be weighed against significantly increased severe hypoglycemia, weight gain, and (in ACCORD) increased total mortality (NNT = 94 for 3.5 years for one excess death) consistently found in all prespecified patient subgroups. Alternative clinical strategies, such as moderate BP control or fenofibrate treatment may reduce microvascular complications independent of glucose control. The data strongly support personalized glucose control goals based on clinical factors and patient preferences for outcomes.