Advances in the treatment of prediabetes.

Type 2 diabetes mellitus (T2DM) is epidemic in most developed and many developing countries. Owing to the associated morbidity, mortality and high costs of care, T2DM is an important global public health challenge and target for prevention. Patients at high risk for T2DM (referred to as having prediabetes) can be easily identified based on fasting glucose levels or responses to an oral glucose tolerance test (OGTT). More recently, glycosylated hemoglobin (i.e. HbA1c, which is also termed A1C in the US) has also been introduced as a diagnostic tool for both prediabetes and diabetes. Such patients are also at risk for cardiovascular disease (CVD). Since obesity and physical inactivity are important risk factors for T2DM, lifestyle interventions, emphasizing modest weight loss and increases in physical activity, should be recommended for most patients with prediabetes. Such interventions are safe and effective and also reduce risk factors for CVD. A number of oral antidiabetic agents have been shown to be effective at delaying onset of T2DM in patients with prediabetes. Thiazolidinediones (TZDs) are the most effective, reducing incident diabetes by up to 80%. Metformin, acarbose and orlistat also reduce incident diabetes, but their efficacy is much lower than the TZDs. Pharmacologic interventions may be appropriate for patients at particular risk for developing diabetes, but the benefits of treatment need to be balanced against the safety and tolerability of the intervention. If pharmacologic treatment is warranted, metformin should be considered first because of its favorable overall safety, tolerability, efficacy and cost profile.