Metformin lowers blood glucose by reducing hepatic glucose output and improving insulin sensitivity without requiring an increase in circulating insulin concentration. We hypothesized that metformin could be used adjunctively with insulin to improve glycemic control in type 1 diabetes mellitus (DM). We conducted a 6-month open-label pilot study in 10 adolescents and young adults with type 1 DM, 19.1 +/- 3.4 years, 4 males, 6 females, and body mass index 26.3 +/- 3.1 kg/m2. Patients started metformin at a dose of 250 mg b.i.d.; the dose was increased until blood glucose was within an optimal target range or a maximum of 2,500 mg/d was reached. Insulin dose was reduced as needed to prevent hypoglycemia. Seven patients had an average decrease in HbA(1c) of 11% from pretreatment. These responders had no change in insulin dose, BMI or lipid levels during the study. Three patients had no improvement of HbA(1c) on therapy. We conclude that some patients with type 1 DM will have improved glycemic control on adjunctive metformin therapy. Evaluation of the long-term benefit and safety of adjunctive therapy in patients with type 1 DM is warranted.