Blood Sugar Lowering Effects of Chlorpropamide and Tolbutamide: A Double Blind Cooperative Study

Hypoglycemic and other effects of tolbutamide, chlorpropamide and placebo administration have been studied in 121 ketoacidosis-resistant diabetic males selected from an initial group of 3,493 patients in eleven Veterans Administration hospitals. A randomized double-blind technic of drug administration was employed. The effects of the drugs on fasting blood sugar (FBS) levels were determined and analyzed statistically. The administration of placebo produced a satisfactory fall in FBS levels in 26 per cent of the patients when used as the initial medication. Tolbutamide was successful in 60 per cent of the trials and chlorpropamide in 83 per cent. When a patient failed to respond to one sulfonylurea drug, he was tried on the other. Under these circumstances, chlorpropamide was more often effective than tolbutamide. Its greater effectiveness was further confirmed by the fact that, compared to tolbutamide, fewer patients required the maximal dosage of chlorpropamide. Primary drug failure with each of these sulfonylurea drugs was 16 per cent. There was no correlation between response and either pretreatment FBS levels or blood drug levels. Blood drug levels were higher for chlorpropamide than for tolbutamide at all levels of dosage. Toxic reactions occurred in less than 3 per cent of the patients, all on chlorpropamide. Secondary failures occurred in less than 10 per cent of the patients. Both of the sulfonylurea drugs studied are effective hypoglycemic agents. The hypoglycemic effect of placebo in one-fourth of the trials necessitates its inclusion in any study of the effectiveness of a therapeutic agent.