Sulfonylureas alone are ineffective in the therapy of insulin-independent diabetes mellitus (IDDM). These agents, however, might serve as an adjunct to insulin treatment if they directly affect insulin binding to its receptor. We studied 11 patients with IDDM to determine whether chlorpropamide acts directly on the insulin receptor and whether it could augment the effect of insulin on glycemic control. Mean tracer insulin binding to both peripheral monocytes and erythrocytes in 11 poorly controlled patients was normal. Optimization of glucose control by continuous subcutaneous insulin infusion for 7–10 days did not alter insulin binding to either cell type. Addition of chlorpropamide, 250–500 mg/day for another 7–10 days did not affect any aspect of insulin binding (tracer binding, number of receptor sites, insulin sensitivity, or affinity) in either cell type. Insulin binding was not changed in one patient after 3 days of 250 mg/day of the drug and in another after 500 mg/day over 3 mo. The sulfonylurea, in addition, provides no additive effect with insulin on blood glucose levels or insulin doses required to maintain euglycemia.

We conclude that short-term use of chlorpropamide in addition to insulin in IDDM does not alter insulin binding to circulating monocytes or erythrocytes. In addition, we were unable to show that this agent is a clinically useful adjunct to insulin in IDDM.

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