Combined continuous subcutaneous insulin infusion (CSII) and metformin (M) was tested in 10 overweighted insulin requiring diabetic patients (body mass index 27.9 +/- 4.9 kg/m2). They were still poorly controlled (HbA1 9.6 +/- 0.8%) despite large doses of lente insulin (Novo) (51.7 +/- 19.6 IU/24 h) injected once daily. With CSII after two weeks on placebo (P) they were enrolled in a randomized double blind cross-over trial with two successive one month periods of M (2550 mg/day) or P. At the end of the two-weeks period CSII--initial P, the daily regular insulin requirement decreased significantly (40.1 +/- 18.1). During M and P body weight and HbA1 were unchanged (respectively 28.6 +/- 6.0 vs 29.0 +/- 59 kg/m2 and 7.7 +/- 1.1 vs 7.7 +/- 0.8%). With M daily insulin requirements decreased significantly (32.0 +/- 16.8 vs 38.4 +/- 18.2 IU, p less than 0.05). During test-meals, M compared to placebo also reduced peripheral free insulin concentrations (-24.9 +/- 26.0%) while plasma glucose and C peptide remained comparable. In the conditions of this study, combined CSII and M reduced the insulin resistance observed in overweighted insulin requiring diabetic patients.