Type II diabetes mellitus is a heterogeneous disease. Selection of either insulin or a sulfonylurea agent in addition to diet is usually made empirically. In patients who fail to respond to either agent alone, the potential benefit of combined insulin and sulfonylurea therapy is unclear. We therefore evaluated nine poorly controlled insulin treated type II diabetic patients after addition of a sulfonylurea agent--glyburide--for four weeks. Glycosylated hemoglobin (HbA1c), serum glucose, and C-peptide responses to oral glucose were evaluated. Based on a reduction of at least 50 mg/dl in the fasting serum glucose (FSG) at the end of the first week of the combination therapy or a FSG of less than 140 mg/dl, two groups were arbitrarily identified: responders (n = 5) and nonresponders (n = 4). Clinical characteristics including mean age, weight, duration of diabetes, daily dose of insulin, and duration of insulin treatment were not statistically different between the two groups. Mean baseline FSG and HbA1c levels were also not statistically different in both groups. An improvement in mean FSG and glucose tolerance occurred in the responders at the end of four weeks of combined therapy (FSG: 291 +/- 25 vs. 189 +/- 6 mg/dl, p less than 0.05; HbA1c 10.76 +/- 0.80 vs. 9.40 +/- 0.21%, p = NS). The nonresponders had no change in glucose tolerance. The mean fasting and stimulated serum C-peptide levels were significantly higher in the responders at week 4 compared with that of the nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)