Trial of an Oral Hypoglycaemic Agent in Diabetes
Authors: F. W. Wolff, G. A. Stewart, M. F. Crowley, A. Bloom
Journal: BMJ (1956)

During an investigation in man of the chemotherapeutic properties of some new sulphonamides, Franke and Fuchs (1955) reported that one, N-butyl-N'-sulphanilylurea (BZ 55), produced hypoglycaemia.Following this observation the compound was examined clinically in diabetics by Franke and Fuchs and by Bertram, Bendfeldt, and Otto (1955).Pharmacological observations were described by Achelis and Hardebeck (1955).Subsequently, another hypoglycaemic agent, N-(4methyl-benzosulphonyt)-N'-butyl-urea (D 860) was dis- covered, on which joint clinical and pharmacological studies were described by Bander et al. (1956).This preparation is not a sulphonamide and has no bacterio- static activity, but its hypoglycaemic properties are similar to those of BZ 55.It was evident from German data that these compounds successfully controlled hyperglycaemia and glycosuria in some diabetics, many of whom were over- weight.This latter fact suggested to us that in this country some of their successful cases might have been treated by diet alone.In view of this we decided to undertake a detailed inpatient study on a group of 45 diabetics, from which we attempted to obtain information on the effect of stopping insulin under conditions of constant diet.If hyperglycaemia and glycosuria persisted BZ 55 was administered orally to ascertain its value as a substitute for injected insulin.In addition, information was sought on the possibility of establishing a short-term test which might enable us to predict the usefulness of this drug in long-term therapy.Studies of free and conjugated sulphonamides in blood and urine were undertaken in an attempt to find correlation between these levels and therapeutic activity.Methods Selection of Cases.-Although an attempt was made to get a representative cross-section of the diabetics attending the hospital clinic, numbering just over a thousand, the necessity of spending two weeks in the wards meant a preponderance of middle-aged or elderly female diabetics in those who were admitted.The majority (34) were out-patients already re- ceiving insulin, the need for which had previously been established.Eleven others had not been receiving insulin.Seven of these were newlv diagnosed diabetics who would normally have received insulin.Four others have had diabetes for several years, controlled by diet alone; but increasing glycosuria, hyperglycaemia, and loss of weight had latterly suggested their need for insulin.A group of six young and brittle diabetics were admitted for a few days only and took part in a short-term test.Design, of Trial.-Onadmission each patient was given a diet suitable for his or her physique and metabolic needs, prepared in a diet kitchen.For out-patients of long stand- ing this was a continuation of the diet to which they were accustomed.These diets have been maintained since the patients were discharged.Apart from the group of young diabetics, patients were kept under observation in the wards for at least two weeks, and were then followed up twice weekly in a special out-patient clinic.For the first five days after admission patients were maintained without insulin on diet alone.Once the initial control period had been completed, a two-day test was performed.On these