Pharmacotherapy of type 2 diabetes mellitus

To review the drug treatments and some of the popular, nontraditional remedies now available for type 2 diabetes mellitus, as well as selected investigational agents; to describe each medication's place in the overall approach to treatment.

English-language journals, abstracts, review articles, and newspaper accounts.

In the past five years, there has been tremendous progress in the pharmacotherapy of diabetes, particularly type 2 diabetes. Several new agents have entered the clinical arena, and many more are in the late stages of investigation leading to approval. Sulfonylureas stimulate the production and release of insulin; these drugs must be used in patients with an intact pancreas. The meglitinides are nonsulfonylurea agents that are also insulin secretagogues. Unlike the sulfonylureas, repaglinide appears to require the presence of glucose to close the adenosine triphosphate-sensitive potassium channels and induce calcium influx. Metformin reduces hepatic glucose production in some patients and increases peripheral glucose utilization, but its use is hampered by a high percentage of adverse reactions. Disaccharidase inhibitors effectively compensate for the defective early-phase insulin release by slowing the production of sugars from carbohydrates. Thiazolidinediones appear to activate peroxisome proliferator-activated receptor gamma, which is involved in the metabolism of lipids. Short-acting insulin and the role of weight-loss agents are also discussed.

The availability of new options for diabetes therapy provides a chance for successful therapy in a larger number of patients. However, it is important to consider how much true benefit these new forms of treatment will have on the diabetic community. The best choice for a patient remains controversial.