Combining sulfonylureas and other oral agents.

Type 2 diabetes mellitus is a progressive disorder, and although oral monotherapy is often initially successful, it is associated with a high secondary failure rate, which contributes to the development of long-term diabetes complications resulting from persistent hyperglycemia. For patients not taking insulin, accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. Low-dose combination therapy may be associated with fewer side effects than higher-dose monotherapy and may achieve similar or better glycemic control. The best-studied combination is that of sulfonylurea compounds plus metformin, a therapeutic approach that addresses both underlying defects in the disorder: insulin deficiency and insulin resistance. Other multidrug regimens under investigation are sulfonylurea compounds plus either alpha-glucosidase inhibitors or thiazolidinediones, and combinations of various insulin-sensitizing agents. For many patients, combination oral therapy may be used appropriately as primary management early in the course of type 2 diabetes, along with diet modification and exercise. Later in the course of the disease, the use of combinations of oral agents may delay the need for insulin while maintaining glycemic control, thus making aggressive oral treatment more acceptable for many patients.