Matching treatment to pathophysiology in type 2 diabetes

Abstract

Background: Because type 2 diabetes is a progressive condition, > 50% of all patients whose disease is initially controlled with diet and exercise will eventually need single or multiple pharmacologic agents to maintain adequate glycemic control. Although current treatment standards require that combination therapy be instituted only after the failure of monotherapy, the results of the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study suggest that aggressive initial treatment is crucial to slowing the evolution of long-term complications associated with this disease. Objectives: This article reviews the diagnosis and classification of type 2 diabetes, describes the multiple defects in glucose metabolism associated with the disease, and discusses the various pharmacologic options for achieving glycemic control in these patients. Methods: The information in this review was compiled through a search of MEDLINE®. Search terms included but were not limited to type 2 diabetes and antihyperglycemic agents. In addition, abstracts were identified using the Web sites of diabetes-related professional organizations. Results: Two pathophysiologic mechanisms, insulin resistance and impaired insulin secretion, are usually present at diagnosis in type 2 diabetes. Several studies have shown that combination therapy with antihyperglycemic agents having different mechanisms of action provides greater efficacy than treatment with single agents. Conclusions: Current research suggests that early aggressive treatment with combination therapy achieves glycemic control at lower doses and with fewer side effects than monotherapy with either component.