Glycemic management in diabetes and the associated cardiovascular risk: are we helping or hurting our patients?

Diabetes, which is a metabolic disorder with multiple comorbidities, increases the risk of cardiovascular disease. Although it was once assumed that controlling plasma glucose levels would reduce diabetes-related morbidity and mortality, recent trials have demonstrated that this is not consistently the case. Data from large, well-designed trials suggest that intensive glycemic therapy may be useful in preventing cardiovascular events if initiated early in the disease course, but may be harmful or not useful if applied to high-risk patients with a longer history of diabetes. Furthermore, the cardiovascular safety of existing individual antihyperglycemic agents remains largely unknown. We review the relationship between glycemic control targets and cardiovascular outcomes, as well as the current understanding of the cardiovascular effects of existing glucose-lowering therapies. This information has affected recommendations for diabetes care in Japan and the United States differently, and supports a more comprehensive and prospective approach to cardiovascular safety assessments of diabetes therapies in the future. Results from ongoing cardiovascular outcomes trials of diabetes medications may help to define optimal glucose-lowering strategies for patients at high risk of cardiovascular complications. Until then, glycemic control targets and the medications used to achieve them should be individualized according to each patient's age, duration of diabetes, risk of hypoglycemia, risk of cardiovascular complications, and life expectancy.