Management of Type 2 Diabetes Mellitus: Is It Time for a Paradigm Shift?

Type 2 diabetes mellitus is a multi-organ disease that results from the combination of insulin resistance and a beta-cell secretory defect. The worldwide prevalence of type 2 diabetes has increased substantially during the past decade, and patients with this disease continue to experience a high incidence of morbidity and mortality. Because the complications associated with this disease affect multiple organ systems and have a dramatic impact on daily life, the importance of lowering glycosylated hemoglobin (HbA(1c)) levels to within the normal range cannot be overemphasized. The introduction in the past decade of several new classes of pharmacological agents to treat patients with type 2 diabetes now provides the opportunity to focus therapy on treating the underlying disease process instead of just reacting to the blood glucose levels. The thiazolidinediones are unique in their ability to modulate free fatty acid metabolism and to improve insulin sensitivity. These agents also exert numerous non-glycemic effects on the vasculature and lipid metabolism and may improve many of the risk factors associated with metabolic syndrome. Data from the United Kingdom Prospective Diabetes Study (UKPDS) group showed that conventional methods of managing type 2 diabetes, including the use of sulfonylureas or biguanides, do not provide long-term glycemic control. Consequently, new treatment paradigms stressing the earlier use of thiazolidinediones, either alone or in combination with metformin, may lead to more durable glycemic control, thus facilitating the reduction of complications in patients with type 2 diabetes.