METABOLIC EFFECTS OF SULFONYLUREAS IN NORMAL MEN and IN VARIOUS TYPES OF DIABETIC PATIENTS

Abstract

The studies described in this report were initiated in an effort to elucidate the mechanism of action of the sulfonylurea compounds. It seemed to us that a broad clinical investigative approach, involving the study of a large number of conditions in which the metabolism of carbohydrate is disturbed, was most likely to eliminate quickly a number of possible modeg of action and to define more sharply the areas upon which further effort should be concentrated. Thus, extensive metabolic-balance studies and numerous individual testing procedures have been performed before, during, and following the administration of carbutamide (BZ-55) and/or tolbutamide (Orinasei) in the following subjects: (1) healthy young men; (2) three middle-aged, obese, stable diabetics; ( 3 ) an unstable diabetic of normal weight; (4) a patient with lipo-atrophic diabetes; ( 5 ) a totally depancreatized woman; (6) patients with coexisting diabetes mellitus and Addison’s disease, familial diabetes and Cushing’s syndrome, and diabetes and panhypopituitarism; and (7) an acromegalic with mild diabetes. Although the data reported below do not define a specific mode of action of the sulfonylurea compounds, they eliminate from consideration a number of important possibilities. Results