Rethinking the use of oral agents in the treatment of type 2 diabetes mellitus

Objective: To present an approach to the management of type 2 diabetes mellitus, focusing on the optimal incorporation of newer oral antidiabetic agents into the management plan. Data Sources: A MEDLINE search (January 1990-December 1997) was conducted for English-language clinical study reports, abstracts, and review articles pertaining to the pathophysiology and management of type 2 diabetes. Reference lists from the publications were searched for other original articles, and other sources were reviewed. Data Extraction: The majority of clinical studies synthesized in this article were double-blind studies. Data and recommendations of the American Diabetes Association and other authoritative groups were also included. Data Synthesis: Impaired pancreatic insulin secretion; resistance of peripheral tissues, particularly skeletal muscle, to the action of insulin; increased hepatic production of glucose; and excessive food intake contribute to hyperglycemia in type 2 diabetes. Oral antidiabetic agents that permit an attack on all four factors are now available. Controlling the blood glucose concentration helps to reduce the morbidity and mortality associated with the microvascular, neurologic, and macrovascular complications of diabetes. Conclusions: Therapeutic agents that target the specific pathophysiologic aspects of type 2 diabetes are now available. These newer agents can be used alone or in combination with each other, older agents, or insulin. This expanded armamentarium should help to improve glycemic control in many patients and to reduce the mortality and morbidity due to this disease.