The stringent targets set for HbA1c levels in type 2 diabetes are currently achieved by fewer than half the patients in the United States. Failure to manage hyperglycaemia in the early stages of disease results in progressive loss of β-cell function, which ultimately necessitates the initiation of insulin therapy. At this point, choices have to be made on whether to continue oral anti-diabetic drug therapy and, if so, with which agent(s). Historically, sulfonylureas have been the mainstay of oral anti-diabetic drug therapy; however, their long-term efficacy in patients with depleted β-cell capacity is doubtful, and other classes of oral anti-diabetic drugs, notably the insulin sensitizers, may prove more reliable. These agents (metformin and thiazolidinediones) appear to provide various benefits over and above sustained glycaemic control, which may variably include reduced loss of β-cell function as well as improvements to cardiovascular risk factors, morbidity, and mortality. Metformin also limits weight gain associated with insulin therapy. This manuscript presents the case that when insulin therapy is initiated it should be tailored to individual needs through combination with one or more insulin sensitizers rather than a secretagogue. Copyright © 2007 John Wiley & Sons, Ltd.