Metformin is often continued when basal insulin is added, with studies demonstrating less weight gain when the two are used together ( 95 ). Insulin secretagogues do not seem to provide for additional HbA 1c reduction or prevention of hypoglycemia or weight gain after insulin is started, especially after the dose is titrated and stabilized. When basal insulin is used, continuing the secretagogue may minimize initial deterioration of glycemic control. However, secretagogues should be avoided once prandial insulin regimens are employed. TZDs should be reduced in dose (or stopped) to avoid edema and excessive weight gain, although in certain individuals with large insulin requirements from severe insulin resistance, these insulin sensitizers may be very helpful in lowering HbA 1c and minimizing the required insulin dose ( 96 ). Data concerning the glycemic benefits of incretin-based therapy combined with basal insulin are accumulating; combination with GLP-1 receptor agonists may be helpful in some patients ( 97 , 98 ). Once again, the costs of these more elaborate combined regimens must be carefully considered.