It is difficult to treat obese non-insulin-dependent diabetic patients (NIDDs) whose glycaemic control remains poor despite maximal oral antidiabetic therapy. We studied the effect of a continuous subcutaneous insulin infusion (CSII) associated with a low-calorie diet and metformin 1,700 mg/day on glycaemic control and basal and stimulated insulin secretion in a series of 82 overweight NIDD before (T1), during CSII (T2), and after CSII withdrawal (T3). Patients were treated for 8 to 23 days with a mean amount of 0.50 +/- 0.02 IU/kg/day. Glycaemic control was very good after 3-5 days of CSII and remained good at T3. At T2, fasting and postprandial plasma C peptide levels decreased significantly. At T3, fasting C peptide was very similar to T1, and postprandial C peptide was significantly higher than at T1. The molar fasting and postprandial plasma C peptide/glycaemia ratios increased significantly at T3. After glucagon injection, the molar delta C peptide/glycaemia ratio was significantly increased at T2 and even higher at T3. At T2, as at T1 and T3, there were significant correlations between fasting and postprandial C peptide levels and between the glucagon-induced C peptide peak and fasting and postprandial C peptide levels. Between T1 and T3 weight changes correlated significantly with the molar fasting C peptide/glycaemia ratio at T1. Twenty-nine of the 30 patients for whom this ratio was > 6.6 x 10(-8) lost weight. The length of CSII treatment did not correlate with weight changes or other biological parameters. This study shows that CSII with moderate amounts of insulin associated with a low-calorie diet and metformin provided rapid glycaemic control, led to weight loss, maintained regulation of insulin secretion and seemed to improve insulin secretion and sensitivity. These results were obtained in only 8 to 10 days.