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) less than 150 mg/dl and
HbA1 levels less than 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 greater than 150 mg/dl and
HbA1 greater than 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.