Preliminary Clinical and Experimental Studies With Chlorpropamide in Diabetes Mellitus

Abstract

The purpose of this communication is to describe our experiences in the clinical management of sixty diabetic patients who have been treated with chlorpropamide for periods varying from a few weeks to six months. In addition, the results of some comparative experiments on the action of tolbutamide and chlorpropamide ilz vitro are given. These suggest that the mode of action of the two drugs upon hepatic enzyme systems is similar, but there seems to be a quantitative difference between them.Clinical observations have been made on sixty adult diabetic patients: twenty-one males and thirty-nine females. In view of earlier experiences with tolbutamide and carbutamide, no attempt has been made to treat any juvenile patient; with few exceptions, the persons included in this series have been middle-aged or elderly. Within these limits a random selection has heen made from patients attending the routine practice of the diabetic service of this hospital.In contrast with earlier clinical trials conducted in the Diabetic and Metabolic Unit of the Alfred Hospital,', many of the patients in this series were not admitted to hospital for continuous observation. I t was felt that experience gained during the past three years was sufficient to enable us to assess the efficacy of chlorpropamide without the need for hospitalization. In consequence, a number of patients were instructed to present the results of urine tests taken a t regular times each day, and spot blood sugar estimations were made at frequent intervals. Subsequent interrogation enabled us to detect the incidence of side effects and the degree of control achieved. A significant number of patients were closely observed, and laboratory investigations were undertaken for evidence of hepatic, renal, and hematological abnormalities. Patients transferred from maintenance doses of insulin were instructed to report daily either in person or by telephone and to present the results of urinalyses performed four times each day.Almost without exception the loading dosage prescribed was 1.0 gm. per day and the maintenance dose 0.5 gm. per day, given in divided doses of 0.25 gm. morning and evening. I n any case that failed to respond, the dosage was raised gradually to 0.75 gm. per day and, in a few instances, to 1.5 gm. per day. Dosage for 1 case was raised to 3 gm. per day for a short time. FIGURE 1 shows the duration of treatment of the patients considered in this series and indicates the number responding to treatment and the number failing to do so. The relatively large number not responding within the first 4 weeks of treatment can be related to several such factors as inappropriate selection of patients, and attempts to transfer cases from insulin therapy. TABLE 1 shows the distribution of the patients by age and sex 810

Studies on oral glucose intolerance in fish

“…The mechanism whereby sulphonylureas exert their hypoglycaemic action in mammals may be absent in fish. The increase in blood amino acids in response to tolbutamide administration to trout may be mediated by sulphonylurea inhibition of gluconeogenesis (Downie et al, 1959). The pre-spawning phase in the female trout is evidently associated with a dramatic change in the endocrine status.…”