Effects of Tolazamide and Exogenous Insulin on Insulin Action in Patients with Non-Insulin-Dependent Diabetes Mellitus

To determine whether sulfonylureas and exogenous insulin have different effects on insulin action, we studied eight patients with non-insulin-dependent diabetes mellitus before and after three months of treatment with tolazamide and exogenous semisynthetic human insulin, using a randomized crossover design. Therapy with tolazamide and therapy with insulin resulted in similar improvement of glycemic control, as measured by a decrease in mean glycosylated hemoglobin (±SEM) from 9.4±0.7 percent to 7.7±0.5 percent with tolazamide and to 7.1±0.2 percent with exogenous insulin (P<0.01 for both comparisons). Therapy with either tolazamide or exogenous insulin resulted in a similar lowering (P<0.05) of postabsorptive glucose-production rates (from 2.3±0.1 to 2.0±0.2 and 1.8±0.1 mg per kilogram of body weight per minute, respectively) but not to normal (1.5±0.1 mg per kilogram per minute). Both tolazamide and exogenous insulin increased (P<0.05) glucose utilization at supraphysiologic insulin concentrations (from 6.2±0.7 to 7.7±0.6 mg per kilogram per minute with tolazamide and to 7.8±0.6 mg per kilogram per minute with exogenous insulin) to nondiabetic rates (7.9±0.5 mg per kilogram per minute). Neither agent altered erythrocyte insulin binding at physiologic insulin concentrations. We conclude that treatment with sulfonylureas or exogenous insulin results in equivalent improvement in insulin action in patients with non-insulin-dependent diabetes mellitus. Therefore, the choice between these agents should be based on considerations other than their ability to ameliorate insulin resistance. (N Engl J Med 1986; 314:1280–6.), CHOOSING the appropriate therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) remains difficult. A proper diet is the cornerstone of treatment. However, it is uncertain whether the next therapeutic step in patients with persistent hyperglycemia should be the administration of oral sulfonylureas or of exogenous insulin.¹ Although both these agents are capable of raising circulating insulin concentrations, they do so by distinctly different mechanisms. Oral sulfonylureas stimulate the release of endogenous insulin,^2,3 thereby maintaining a portal-peripheral venous insulin gradient. In contrast, treatment with exogenous insulin presumably raises peripheral venous and portal venous insulin concentrations proportionately, producing relative peripheral hyperinsulinemia.⁴ Because…