Early and intensive therapy for management of hyperglycemia and cardiovascular risk factors in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) results in significant morbidity and mortality. Results of recent randomized controlled trials demonstrated the ability of early and intensive therapy to reduce the risk of microvascular complications. However, controversy surrounds the ability of such therapy to reduce the risk for macrovascular complications.

OBJECTIVES: This article reviews results from recent clinical trials in patients with T2DM as well as extended follow-up of earlier trials to determine if early, intensive, and individualized therapy aimed at the underlying pathogenesis of the disease could decrease the risk for long-term complications, including cardiovascular disease (CVD).

METHODS: Information was obtained by a search of the PUBMED and EMBASE databases using the search terms type 2 diabetes mellitus, glycosylated hemoglobin, pathophysiology of type 2 diabetes, glycemic control, early intervention, multifactorial intervention, cardiovascular disease, β-cell function, and antidiabetes therapy for the period between 1995 and 2010. Articles dealing with outcomes trials, impact of therapy on microvascular and macrovascular complications, effects of therapeutic agents on the pathophysiology of T2DM, and the impact of agents on CV risk factors were then preferentially selected for in-depth review.

RESULTS: Large-scale clinical trials in patients with T2DM, although largely negative at 5 years for macrovascular end points, suggested benefit for patients with a shorter duration of T2DM (ie, <10 years) and still supported a treatment strategy of early, intensive, and individualized therapy to prevent long-term complications of the disease. In Steno-2, after 13 years of follow-up, early, intensive, multifactorial therapy was associated with a 56% lower risk of all-cause death (P = 0.02) and a 57% lower risk of death from CVD (P = 0.04). In the 10-year follow-up to the United Kingdom Prospective Diabetes Study, intensive therapy was associated with a significant 15% reduction in the risk of myocardial infarction (P = 0.01) and a significant 13% reduction in the risk of death from any cause (P = 0.007). Therapy should be aimed at correcting underlying pathophysiologic defects, including β-cell failure and insulin resistance, and should also correct underlying risk factors for CVD whenever possible.

CONCLUSIONS: Early and intensive antidiabetes treatment was recommended in patients with T2DM, particularly those with a shorter duration of disease and without a history of CVD. The goal was to safely lower glycosylated hemoglobin to <7%, therefore providing beneficial effects on the risk for complications. Hypoglycemia should be avoided. In addition, less aggressive treatment might be suitable for older patients with longstanding diabetes and a history of CVD events. Clinical trial results also provided support for a second important aspect of individualized treatment for patients with T2DM-multifactorial intervention aimed at controlling CVD risk factors.