Adjuvant Therapy with Tolazamide and Insulin Improves Metabolic Control in Type I Diabetes Mellitus

Sulfonylurea agents have been well documented to be effective in type II diabetes mellitus by increasing insulin secretion as well as by enhancing cellular binding of endogenous insulin. We have examined in 20 type I diabetic subjects the efficacy of tolazamide, a common sulfonylurea agent, as adjuvant therapy in combination with an appropriate diet and insulin. This regimen decreased the insulin dose while continuing to maintain adequate metabolic control, as reflected by fasting plasma glucose (FPG) <150 mg/dl and HbA₁ levels <9%, and reduced number of hypoglycemic episodes to almost nil in a group of subjects with adequate metabolic control before institution of combination therapy. In subjects in whom metabolic control was inadequate (FPG > 150 mg/dl and HbA¹ > 9%) with insulin alone, the adjuvant therapy with tolazamide improved or normalized hyperglycemia and HbA¹. In 13 subjects in whom adequate metabolic control was achieved with combination therapy, metabolic control worsened on withdrawal of tolazamide while continuing insulin in the same dosage and adequate metabolic control promptly returned on reinstitution of combination therapy with insulin and tolazamide. In the remaining seven subjects, metabolic control remained adequate with combination therapy during the 4–10-mo follow-up period. This study therefore demonstrates that combination therapy with sulfonylurea agent and insulin may be beneficial in management of type I diabetes. Furthermore, this regimen may be helpful in prevention of extreme plasma glucose excursions observed in brittle diabetic individuals. A larger, long-term clinical trial with this regimen in type I diabetic subjects must be undertaken to establish this preliminary finding.