Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes

Abstract: Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the pediatric population, there is limited information about the relative effectiveness of treatment approaches. This article describes the rationale and design of a National Institutes of Health-sponsored multi-site, randomized, parallel group clinical trial designed to test the hypothesis that aggressive reduction in insulin resistance early in the course of T2DM is beneficial for prolongation of glycemic control, as well as improvement in associated abnormalities and risk factors. Specifically, the trial compares treatment with metformin with two alternate approaches, one pharmacologic (combining metformin treatment with rosiglitazone) and one combining metformin with an intensive lifestyle intervention program. The in Adolescents and Youth (TODAY) study recruits 800 patients over a 4-yr period and follows them for a minimum of 2 yr and maximum of 6 yr. Patients are 10–17 yr of age, within 2 yr of diagnosis of diabetes at the time of randomization, lack evidence of autoimmunity, and have sustained C-peptide secretion. The primary outcome is time to loss of glycemic control, defined as a hemoglobin A1c >8% for 6 consecutive months. Secondary outcomes include the effect of the alternative treatments on insulin secretion and resistance, body composition, nutrition, physical activity and fitness, cardiovascular risk monitoring, microvascular complications, quality of life, depression, eating pathology, and resource utilization. TODAY is the first large-scale, systematic study of treatment effectiveness for T2DM in youth. When successfully completed, this study will provide critical new information regarding the natural history of T2DM in youth, the benefits of initiating early aggressive treatment in these patients, and the efficacy of delivering an intensive and sustained lifestyle intervention to children with T2DM.