The heterogeneous pathogenesis and progressive natural history of type 2 diabetes mellitus (T2DM) contrive a formidable therapeutic challenge. Dual endocrine deficits of impaired insulin action (insulin resistance) and inadequate insulin secretion create an environment of chronic hyperglycaemia and general metabolic disarray. This inflicts a heavy burden of morbidity and premature mortality from cardiovascular diseases, microvascular disorders (e.g. retinopathy and nephropathy) and neuropathic conditions. Improving glycaemic control delays the onset and reduces the severity of these long-term complications. However, even with intensive use of current antidiabetic agents more than 50% of T2DM patients suffer poor glycaemic control and 18% develop serious complications within six years of diagnosis. Clearly, there is a need for new antidiabetic agents.