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

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Abstract
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.