OBJECTIVE: This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period. RESULTS: Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of -4.3 +/- 9.9 units (-7.8 +/- 18%) compared with an increase with placebo treatment of 1.7 +/- 8.3 units (2.8 +/- 12.7%) (P = 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of -2.6 +/- 3.2 units (-7.9 +/- 23.8%) compared with an increase with placebo treatment of 1.9 +/- 5.7 units (8.8 +/- 27.1%) (P = 0.023). HbA(1c) remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (<60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P = 0.04) and LDL cholesterol (P = 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P = 0.069). CONCLUSIONS: Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.