The Treat-to-Target Trial and related studies

To describe the rationale for, and the findings of, the Treat-to-Target Trial and to compare its results with those of two subsequent studies based on the same concepts.

The 24-hour pattern of hyperglycemia in type 2 diabetes is presented, and its separate components are identified in an attempt to help optimize therapeutic interventions for diabetes. In addition, the treat-to-target concept, including glycemic outcomes and potential adverse effects, is discussed.

Using a hemoglobin A1c (A1c) value of 7% as a treatment goal based on evidence from interventional studies and a fasting plasma glucose level of 100 mg/dL as a target for titration of dosage of basal insulin, the Treat-to-Target Trial tested two hypotheses. It confirmed that addition of basal insulin to previously unsuccessful oral therapies can, using a simple algorithm, restore glycemic control to 7% A1c or better in most patients with type 2 diabetes. It also confirmed that a long-acting insulin analogue, glargine, causes less hypoglycemia than human NPH insulin when used in this way. Two subsequent studies using similar treatment algorithms showed comparable ability to improve glycemic control but also demonstrated more frequent unwanted effects of insulin treatment when a different comparator regimen was used to initiate therapy than when a glargine-based regimen was used.

Initiation of insulin therapy with structured titration to glycemic targets can frequently, but not always, restore glycemic control in patients with type 2 diabetes when orally administered agents are no longer successful alone. Future trials should include hypoglycemia and weight gain as specific, objectively measured endpoints to assess their importance as adverse effects of titrating insulin dosage to target. Studies are needed to assess ways to control postprandial as well as basal hyperglycemia and thus enable almost all patients with type 2 diabetes to reach A1c targets.