Matching treatment to pathophysiology in type 2 diabetes

Background: Because type 2 diabetes: is a progressive condition, > 50% of a ll patients: whose disease is initially controlled with diet and exercise w ill eventually need single or multiple pharmacologic agents to maintain ade quate glycemic control. Although current treatment standards require that c ombination therapy be instituted only after the failure of monotherapy, the results of the Diabetes Control and Complications Trial and the United Kin gdom Prospective Diabetes Study suggest that aggressive initial treatment i s crucial to slowing the evolution of long-term complications associated wi th this disease. Objectives: This article reviews the diagnosis and classification of typo 2 diabetes, describes the multiple defects in glucose metabolism associated with the disease, and discusses the various pharmacologic options for achie ving glycemic control in these patients. Methods: The information in this: review was compiled through a search of M EDLINE(R). Search terms included but were not limited to type 2 diabetes an d antihyperglycemic agents. In addition, abstracts were identified using th e Web sites of diabetes-related professional organizations. Results: Two pathophysiologic mechanisms, insulin resistance and impaired i nsulin secretion, are usually present at diagnosis in type 2 diabetes. Seve ral studies have shown that combination therapy with antihyperglycemic agen ts having different mechanisms of action provides greater efficacy than tre atment with single agents. Conclusions: Current research suggests that early aggressive treatment with combination therapy achieves glycemic control at lower doses and with fewe r side effects than monotherapy with either component.