Pharmacotherapy of type 2 diabetes mellitus

OBJECTIVE: To review the drug treatments and some of the popular, nontradit ional remedies now available for type 2 diabetes mellitus, as well as selec ted investigational agents; to describe each medication's place in the over all approach to treatment. DATA SOURCES: English-language journals, abstracts, review articles,and new spaper accounts. DATA SYNTHESIS: In the pat five years, there has been tremendous progress i n the pharmacotherapy of diabetes, particularly type 2 diabetes. Several ne w agents have entered the clinical arena, and many more are in the late sta ges of investigation leading to approval. Sulfonylureas stimulate the produ ction 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 req uire the presence of glucose to close the adenosine triphosphate-sensitive potassium channels and induce calcium influx. Metformin reduces hepatic glu cose production in some patients and increases peripheral glucose utilizati on, but its use is hampered by a high percentage of adverse reactions. Disa ccharidase inhibitors effectively compensate for the defective early-phase insulin release by slowing the production of sugars from carbohydrates. Thi azolidine diones appear to activate peroxisome proliferator-activated recep tor gamma, which is involved in the metabolism of lipids. Short-acting insu lin and the role of weight-loss agents are also discussed. CONCLUSIONS: 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 treatmen t will have on the diabetic community. The best choice for a patient remain s controversial.