Background: Diabetes mellitus (DM) is a serious, chronic metabolic disease affecting approximately 17 million Americans. The microvascular and macrovascular complications of DM are associated with considerable morbidity and mortality.
Objectives: This article reviews the importance of normalizing blood glucose values to reduce the risk of microvascular and macrovascular complications, discusses available treatment options for type 2 DM, and explores the rationale for combination therapy that includes a thiazolidinedione.
Methods: Relevant articles were selected from published reports and conference presentations from the last 10 years on oral agents for monotherapy and combination therapy for type 2 DM. Other sources were identified from the reference lists of selected articles.
Results: Choices for the pharmacologic treatment of hyperglycemia in patients with type 2 DM include thiazolidinediones, insulin secretagogues, biguanides, and alpha-glucosidase inhibitors. Each of these drug classes is effective in lowering blood glucose concentrations; however, they have distinctly different mechanisms of action that target various pathophysiologic causes of type 2 DM and have different adverse-event profiles. in addition, several of these agents provide unique benefits unrelated to their hypoglycemic effects. Thiazolidinediones offer the therapeutic benefits of increasing insulin sensitivity and perhaps preserving beta-cell function. Use of a thiazolidinedione from the time type 2 DM is diagnosed improves insulin sensitivity, thereby improving glycemic control and minimizing complications. Over time, however, many patients with type 2 DM are unable to maintain adequate glycemic control (ie, glycosylated hemoglobin [HbA(1c)] <7%) with monotherapy. Combination therapy with agents from different classes may be necessary to achieve blood glucose control through an additive reduction in HbA(1c). The combination of a thiazolidinedione and a biguanide reduces hyperglycemia, hyperinsulinemia, and insulin resistance and improves factors that have been implicated in the pathogenesis of cardiovascular complications.
Conclusions: Patients with type 2 DM who are not able to maintain their HbA(1c). <7% with monotherapy should be considered candidates for combination therapy. Appropriate combination therapy includes treatment with 2 or more agents with different, complementary mechanisms of action. For example, the combination of a thiazolidinedione and a biguanide improves insulin sensitivity and lowers blood glucose through complementary pathways, and therefore produces an additive effect.