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September 1960

Oral Hypoglycemic Agents

Author Affiliations


From the Medical Service, VA Research Hospital and the Department of Medicine, North-western University Medical School.

Arch Intern Med. 1960;106(3):345-353. doi:10.1001/archinte.1960.03820030033007

In early 1942 while investigating the effect of isopropylthiodiazole (2254 RP) in typhoid fever, M. Janbon and co-workers in the Infectious Disease Clinic at Montpellier Medical School in France found that this sulfanilamide derivative produced signs and symptoms resembling hypoglycemia. This was confirmed by the finding of low blood glucose concentrations, and in some persons the administration of intravenous glucose resulted in alleviation of symptoms. A. Loubatieres of the Laboratory of Applied Physiology of the same school was consulted and in June of 1942 commenced the first of a number of studies of these compounds. It soon became apparent that 2254 RP was the first of a number of sulfonylurea derivatives that produced hypoglycemia.

In the 17 years since Janbon's observations, five compounds have been studied extensively and received clinical trial. These compounds are carbutamide, tolbutamide, chlorpropamide, metahexamide, and phenformin hydroxide (N'-β-phenethylbiguanide). Their formulas are given in the Figure. Two