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Background: Type 2 diabetes mellitus (T2DM) is a leading cause of morbidity and mortality that places a substantial economic and health burden on the public. Successful management of T2DM requires strict control of glycemia as well as other risk factors to prevent disease progression. Despite the availability of multiple classes of oral antidiabetic drugs and insulin, the majority of patients fail to attain or maintain tight glycemic control over time, raising their risk of serious microvascular and macrovascular complications.Scope: This review briefly outlines current standards of diabetes treatment and explores several new and investigational approaches. It is based on MEDLINE literature searches (1966–August 2006) and on abstracts from the American Diabetes Association Scientific Sessions (2002–2006) and the European Association for the Study of Diabetes Annual Meetings (1998–2006). Articles concerning basic science, preclinical, and clinical trial results were selected for this review based on their originality and relevance.Findings: Medical professional societies and other specialist groups have proposed a series of practical steps to enable more patients with T2DM to reach treatment goals. Among their most important recommendations is a call for new drugs to stabilize or reverse the progressive pancreatic islet-cell dysfunction that characterizes the disease. New modalities, such as incretin mimetics and DPP-4 inhibitors, are now emerging from clinical development and will provide patients with more treatment options.Conclusions: It appears likely that early and aggressive treatment with multiple drug combinations will become more common in the management of T2DM. The new treatment modalities discussed here offer hope for improved outcomes and for meeting the considerable public health challenges posed by this complex condition. However, long-term studies are needed to determine durability of treatment effects, as well as the ultimate role of these new agents in the management of patients with T2DM. [ABSTRACT FROM AUTHOR]