Type II diabetic subjects with secondary failure: treatment with prebreakfast mixed ultralente and regular insulin...

Combination therapy with sulfonylurea and insulin is reported to be effective in several recent reports on the management of non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea. Most of these studies used insulin twice daily, however, and hence failed to offer a significant practical advantage over insulin therapy alone. Since a subcutaneous injection of Ultralente insulin exerts its peak effect between 16 and 18 hours after injection, its prebreakfast administration is likely to inhibit overnight hepatic glucose production, which is a primary modulator of fasting plasma glucose, a major determinant of diurnal glycemia in NIDDM: Moreover, the simultaneous administration of regular insulin tends to improve glycemia during the premeal and immediate postmeal period before the onset of sulfonylurea-induced insulin secretion.

We assessed the efficacy of a prebreakfast subcutaneous injection of mixed Ultralente and regular insulin in conjunction with prior sulfonylurea therapy in 20 NIDDM subjects after precise documentation of secondary failure to these agents initially for the period of 3 months, followed by a long-term evaluation for up to 2 years.

Metabolic control improved significantly as reflected by a decline in fasting plasma glucose (FPG) and HbA1c concentrations (FPG, 14.4 mmol/L +/- 0.4 vs 79 mmol/L +/- 0.3 mM/L; HbA1c, 11.7% +/- 0.3% vs 8.8% +/- 0.1%; P less than .001 for both comparisons). Serum cholesterol and triglycerides decreased as well, although the change was significant for triglycerides alone. Body weights and blood pressure remained unaltered. Furthermore, metabolic control appeared to remain in the same range during the long-term follow-up period.

Adjuvant therapy with sulfonylurea and a single prebreakfast subcutaneous injection of mixed Ultralente and regular insulin may be an effective and practical therapeutic option in the management of NIDDM with secondary failure to sulfonylurea.