THE PRIMARY dysfunction that determines the degree of hypoglycemia in type 2 diabetes mellitus, ie, progressive loss of β-cell function, clearly dictates that insulin treatment will ultimately prove necessary to preserve glycemic control in patients with long-standing disease. Soon after the initial diagnosis of type 2 diabetes, during the period of retained but lessened β-cell function, insulin monotherapy may only be appropriate in special circumstances, eg, in patients with extreme hyperglycemia, glucose toxicity, islet cell antibodies, a history of ketoacidosis, or pregnancy. However, the evidence-based literature is clear that combination therapy of oral agents with insulin is superior to insulin therapy alone in most moderate to advanced cases of type 2 diabetes.1- 3 Combination therapy with insulin and oral agents can limit weight gain and insulin dosage, and provide benefits that insulin alone cannot provide, such as reducing high triglyceride and very-low-density lipoprotein cholesterol levels, which are markers for diabetic complications. In all studies, combination therapy produced better glycemic control than insulin monotherapy. Although my colleagues suggest that there is no ceiling for insulin dosage, it is also true that high dosages of insulin increase the risk of severe hypoglycemia. Hypoglycemia is a barrier to glycemic control, and a burden to the patient and the health care system. Despite the reduced risk of hypoglycemia associated with new analogue insulin formulations, hypoglycemia continues to be a complication of therapy that must be addressed.