Objective To describe treatment regimens in youth with type 2 diabetes and examine associations between regimens, demographic and clinical characteristics, and glycemic control. Research Design And Methods This report includes 474 youth with a clinical diagnosis of type 2 diabetes who completed a SEARCH for Diabetes in Youth study visit. Diabetes treatment regimen was categorized as lifestyle alone, metformin monotherapy, any oral hypoglycemic agent (OHA) other than metformin or two or more OHAs, insulin monotherapy, and insulin plus any OHA(s). Association of treatment with demographic and clinical characteristics (fasting C-peptide [FCP], diabetes duration, and self-monitoring of blood glucose [SMBG]), and A1C was assessed by x2 and ANOVA. Multiple linear regression models were used to evaluate independent associations of treatment regimens and A1C, adjusting for demographics, diabetes duration, FCP, and SMBG. Results Over 50% of participants reported treatment with metformin alone or lifestyle. Of the autoantibody-negative youth, 40% were onmetformin alone, while 33% were on insulin-containing regimens. Participants on metformin alone had a lower A1C (7.0±2.0%, 53±22mmol/mol) than those on insulin alone (9.2±2.7%, 77± 30 mmol/mol) or insulin plus OHA (8.6 ± 2.6%, 70 ± 28 mmol/mol) (P < 0.001). These differences remained significant after adjustment (7.5 ± 0.3%, 58 ± 3 mmol/mol; 9.1±0.4%, 76±4mmol/mol; and 8.6±0.4%, 70±4mmol/mol) (P < 0.001) andweremore striking in those with diabetes for ‡2 years (7.9±2.8, 9.±6 2.8, and 9.8 ± 2.6%). Over one-half of those on insulin-containing therapies still experience treatment failure (A1C ‡8%, ±4 mmol/mol). Conclusions Approximately half of youth with type 2 diabetes were managed with lifestyle or metformin alone and had better glycemic control than individuals using other therapies. Those with longer diabetes duration in particular commonly experienced treatment failures, andmore effective management strategies are needed.