Different Amounts of Insulin Secretion Following an Equal Total Decrease of Blood Glucose as an Indication of Possible Extrapancreatic Activities of Different Sulfonylurea Drugs

Equipotent doses of the sulfonylurea drugs tolbutamide, glibornuride, and glibenclamide were determined for normal persons and for dogs by means of a maximum blood glucose reduction of 30% or 23%, respectively, as a criterion of drug potency. In individuals and experimental animals the hypoglycemic effects of different sulfonylurea drugs in equipotent doses were identical with respect to the maximum percent blood glucose reduction, as well as to the integrated area of the percent decrease of blood glucose. The difference observed between the sulfonylurea compounds described, concerned their insulin-stimulating effects. Thus, tolbutamide induced a lower peripheral insulin level than glibenclamide to obtain the same blood glucose decrease. Glibornuride and tolbutamide had similar effects. In individuals and experimental animals, the ratios of the integrated areas of blood glucose reduction/insulin increase were identical for each of the sulfonylurea drugs, in spite of the differences between blood glucose reduction and insulin increase. There were marked variations, however, between the different sulfonylurea drugs, in special with regard to the time periods at which maximum increments in insulin secretion were established: the rapidly exhibited insulin secretion in response to both tolbutamide and glibornuride on the one hand and the delay in the insulin secretion following glibenclamide.