Update on type 2 diabetes mellitus: understanding changes in the diabetes treatment paradigm.

Type 2 diabetes mellitus, which is increasingly prevalent in the United States and responsible for the bulk of diabetes-related healthcare costs, has not been adequately managed over the long term with the most commonly prescribed oral hypoglycaemic medications. Although there is evidence that successful management of type 2 diabetes must address both beta-cell deficiency and insulin resistance, most oral agents now prescribed do not prevent the progressive loss of beta-cell function that has traditionally continued during treatment. Increasingly aggressive management guidelines have led to the recommendation that metformin therapy be initiated along with lifestyle modification at the time of diagnosis. It seems unlikely, however, that this strategy will impede the progression of beta-cell dysfunction. Treatment paradigms are emerging that combine routinely used drug categories with newer agents based on the incretin pathway to achieve long-term glycaemic control. The current review discusses the clinical implications of these newer therapeutic alternatives, which enhance insulin secretion through glucose-dependent and physiologic mechanisms.