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There are few biomarkers of glycemic response among youth with T2D, despite increasing disease prevalence and suboptimal response to approved therapies. We hypothesized that plasma metabolites may predict glycemic outcomes in youth-onset T2D. We measured 480 metabolites in fasting plasma samples in the Treatment options for T2D in Adolescents and Youth (TODAY) study (n= 391), in which youth with T2D aged 10-17 years were randomized to metformin alone, metformin+ rosiglitazone, or metformin+ intensive lifestyle intervention. Metabolite associations with loss of glycemic control (defined as HbA1c≥ 8% for 6 months or need for insulin therapy) were modeled using Cox proportional hazards regression adjusted for baseline age, sex, race/ethnicity, BMI, treatment group, and fasting glucose. Loss of glycemic control was observed in 150 of 391 youth (mean 2.6 years). Baseline levels of 11 …