Glycemic control and cardiovascular disease: what's a doctor to do?

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in individuals with diabetes mellitus. Moreover, rates of CVD mortality are two to four times higher in diabetes than in those without diabetes. It was conventional thinking that achieving near-normoglycemia would help reduce CVD risk and overall mortality in type 2 diabetes mellitus. Several recent large trials attempted to answer this question using a randomized control trial design with a conventional therapy and an intensive control arm. Surprisingly, these trials did not demonstrate neither mortality nor a CVD advantage with intensive glycemic control. Moreover, some studies (e.g., the ACCORD [Action to Control Cardiovascular Risk in Diabetes] study) showed increased mortality in the intensive control arm. In this review, our goal is to summarize the findings of the major trials in this field and to explore the potential reasons for why these trials had largely negative results. We conclude with some lessons that may be applied to the clinical management of patients with diabetes.