Twenty non-insulin-dependent diabetic patients on insulin therapy for more than 2 months due to secondary failure to oral hypoglycemic agents (OHA) were additionally treated with gliclazide, 80 mg b.i.d., for 1 month and 160 mg b.i.d. for a further 2 months, while reducing insulin dose gradually according to glycemic control. At the end of the first month, fasting blood glucose had decreased from 12.8 +/- 0.7 to 9 +/- 0.8 mM (mean +/- standard error; P < 0.005) and thereafter remained stable. Insulin requirements decreased from 34.2 +/- 2.5 to 18.3 +/- 3.2 U/day (P < 0.001). Three patients were able to cease insulin treatment altogether. A direct correlation was found between final insulin dose and previous duration of infusion monotherapy (r = 0.52; P < 0.05). C-peptide/glucose score (fasting C-peptide/fasting BG x 100) increased from 0.11 +/- 0.03 to 0.21 +/- 0.05 (P < 0.05). We conclude that combined therapy reduces insulin requirement by increasing endogenous secretion, which may mainly affect hepatic glucose production as indicated by greater improvement in fasting vs. post-prandial blood glucose. This therapy could avoid hyperinsulinemia, which has been reported to be involved in macrovascular complications, and the additional haemovascular properties of gliclazide could make it more effective in such a combination.