Summary

Combined oral agent therapy offers superior efficacy and an opportunity to minimize side effects. In selecting oral combinations, an important objective is minimizing the number of tablets needed and their cost, and this practical imperative has led to various formulations, including several with two agents in a single tablet. Early use of combination therapy is recommended in consensus algorithms (67). Combining oral agents even with the addition of incretin mimetics may delay the need for insulin injections, but when insulin is needed it should be promptly started. Continuing oral agents while starting a single evening injection of insulin is a simple and reliable way to make the transition to insulin therapy (68). Use of inhaled insulin and incretin mimetics may represent a reasonable alternative for some patients for a while. Poor glycemic control with a single injection plus a secretagogue, insulin-assisting agents, or both, may signal a decline of endogenous insulin and call for further daily injections often to control prandial hyperglycemia (69); at this point secretagogues are usually stopped. Similarly, poor glycemic control with two or more injections of insulin alone may call for addition of an insulin-assisting agent, such as metformin or a thiazolidinedione. The glycemic and non-glycemic benefits, as well as risks, of combining insulin-assisting agents while intensifying insulin therapy must be better defined. It seems likely that such combinations will be necessary for most patients with type 2 diabetes to achieve the currently recommended minimum glycemic target (< 7% HbA1c), and especially the more ambitious targets that have been proposed (< 6.5% or 6% HbA1c). Additional oral or injected agents, such as pramlintide and incretin mimetics, are becoming available and offer further options for combination therapy to achieve the glycemic targets of the future.

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