BACKGROUND To search for the mechanisms of secondary oral hypoglycemic agent (OHA) failure in non-insulin-dependent diabetic (NIDD) and to identify the effects of insulin therapy on these patients, we observed their pancreatic beta-cell function and metabolic parameters. METHODS The clinical characteristics and C-peptide responses to glucagon were analyzed in 37 NIDD with secondary OHA failure. All patients received insulin therapy and we measured their fasting plasma glucose (FPG), body mass index (BMI) and glycohemoglobin (HbA1C) levels at 3 months, their serum triglyceride and cholesterol levels at 6-12 months and performed glucagon tests at 0.5-29 months. RESULTS Poor beta-cell function was observed in 11 (29.7%) patients (Group A) and fair beta-cell function in 26 (70.3%) patients (Group B). The mean age at diagnosis, the number of years since diagnosis of diabetes, FPG levels and HbA1C levels were similar in both groups. However, the patients in Group A had a lower average BMI (18.9 +/- 0.7 vs 22.1 +/- 0.6 kg/m2, p = 0.006) than those of Group B. After insulin therapy, the FPG levels (215 +/- 14 vs 282 +/- 12 mg/dL, p < 0.001) and HbA1C levels 9.2 +/- 0.5 vs 11.6 +/- 0.5%, p < 0.001) of both groups decreased but the BMI (23.1 +/- 0.7 vs 21.6 +/- 0.7 kg/m2, p < 0.001) increased significantly. However, the blood lipid levels and beta-cell function did not change. The beta-cell function was still poor in 5 out of 6 patients in Group A, but it was unchanged in all patients in Group B. CONCLUSIONS About 1/3 of NIDD with secondary OHA failure are permanently insulin deficient and need long-term insulin treatment.