Intensive Glycemic Control and Cardiovascular Outcomes: VADT
The Veterans Affairs Diabetes Trial (VADT) randomized participants with type 2 diabetes uncontrolled on insulin or maximal dose oral agents (median entry A1C 9.4%) to a strategy of intensive glycemic control (goal A1C 6.0%) or standard glycemic control, with a planned A1C separation of at least 1.5%1 Medication treatment algorithms were used to achieve the specified glycemic goals, with a goal of using similar medications in both groups; other CVD risk factors were treated aggressively and equally in both groups Median A1C levels of 6.9 and 8.4% were achieved in the intensive and standard arms, respectively, within the first year of the study; the primary outcome was a composite of CVD events; cumulative primary outcome was nonsignificantly lower in the intensive arm The evidence for a cardiovascular benefit of intensive glycemic control primarily rests on long-term follow-up of study cohorts treated early in the course of type 1 and type 2 diabetes and subset analyses of ACCORD, ADVANCE, and VADT. A recent group-level metaanalysis of the latter three trials suggests that glucose lowering has a modest (9%) but statistically significant reduction in major CVD outcomes, primarily nonfatal MI, with no significant effect on mortality A prespecified subgroup analysis suggested that major CVD outcome reduction occurred in patients without known CVD at baseline (HR 0.84 [95% CI 0.74–0.94]).2 Conversely, the mortality findings in ACCORD and subgroup analyses of VADT suggest that the potential risks of very intensive glycemic control may outweigh its benefits in some patients, such as those with very long duration of diabetes, known history of severe hypoglycemia, advanced atherosclerosis, and advanced age/frailty44References Duckworth W, Abraira C, Moritz T, et al., for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139. Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009;52:2288–2298.