Combination therapy for type 2 diabetes.

Abstract

OBJECTIVE: To discuss a rational approach to improvement of glycemic control in patients with type 2 diabetes mellitus with use of combination therapy. METHODS: We review the mechanisms of action and clinical applications for the various antidiabetic agents alone and in various combinations. Relevant studies in the literature are reviewed. RESULTS: Although diet and exercise remain the cornerstones of treatment, in most patients with type 2 diabetes, pharmacologic agents are needed to achieve optimal glycemic control and likely reduce the incidence of microvascular and possibly macrovascular complications as well. Sulfonylureas have long been the foundation of oral pharmacologic therapy and provide adequate glycemic control for most patients for 5 to 10 years or longer. In the past, when treatment with sulfonylureas was no longer effective, insulin therapy was inevitable. With the approval of several new pharmacologic agents for the treatment of type 2 diabetes, however, the addition of one or more orally administered agents to sulfonylurea therapy or use of other oral combination therapy is rapidly evolving as a means of optimizing glycemic control. In many patients, combination therapy can delay the need to add or switch to insulin, or it can enhance glycemic control in patients already receiving insulin. In selected patients treated solely with insulin, discontinuation of insulin treatment and reinitiation of oral therapy may even be possible. CONCLUSION: Currently, four classes of orally administered antidiabetic agents are available for use in patients with type 2 diabetes: insulin secretagogues, biguanides, a-glucosidase inhibitors, and thiazolidinediones. By taking advantage of differing mechanisms of action, combination therapy is evolving as a means of optimizing glycemic control in patients in whom a single agent or insulin is inadequate. Combinations of orally administered agents can often delay the need for insulin or in combination with insulin aid in achieving glycemic goals. Continuing research will help optimize combination therapies even further.