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 less than 0.01 for both comparisons).
Therapy with either
tolazamide or exogenous
insulin resulted in a similar lowering (P less than 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 less than 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.