Exaggerated insulin resistance during puberty may contribute to poor metabolic control in adolescents with type 1 diabetes (T1D). The objective of this study was to determine if the addition of pioglitazone to usual insulin therapy leads to improved glycemic control (HbA1c) in pubertal T1D patients. We conducted a randomized, placebo-controlled, double-blind 6 month trial of 30 mg pioglitazone versus placebo in 35 adolescents with T1D, high insulin dose (>0.9U/kg/day) and suboptimal glycemic control (HbA1c > 7.5%). After 6 months both groups had improved metabolic control (p < 0.05); (mean change in HbA1c in Pioglitazone group -0.4 +/- 0.9 versus -0.5 +/- 1.2% in Placebo group). There were no significant differences between the two groups at 6 months in either HbA1c or insulin dose. BMI SDS increased by 0.3 in the Pioglitazone group, and remained unchanged in the Placebo group (p = 0.01). The Pioglitazone group had a small, but significant improvement in cholesterol and LDL compared to the Placebo. We conclude that adjunctive pioglitazone therapy was not effective in improving glycemic control in adolescents with T1D.