über Synthetisch Dargestellte Körper mit Insulinartiger Wirkung Auf den Normalen und Diabetischen Organismus

Metformin: historical overview

“…2), especially the immature seed pods [6]. In 1918, guanidine was Galega officinalis used to treat symptoms of diabetes (Hill) [3] 1844-1861 Identification and synthesis of guanidine (Strecker) [6] 1878-1879 Synthesis of biguanide (Rathke) [6] 1918 Guanidine lowers blood glucose in animals (Watanabe) [7] 1922 Synthesis of dimethylbiguanide (Werner and Bell) [17] 1926-1928 Galegine and synthalin lower blood glucose in animals and humans [8][9][10][11][12][13] 1929 Metformin and other biguanides lower blood glucose in animals (Hesse and Taubmann; Slotta and Tschesche) [18,19] 1930s Use of guanidine derivatives to treat diabetes initially grows then declines due to toxicity and also availability of insulin [6] 1944-1947 Guanidine-based antimalarial agent, proguanil (Paludrine), lowers blood glucose in animals [20, 21] 1949-1950 Dimethylbiguanide (flumamine) tested as potential antimalarial agent and used to treat influenza in Philippines. Also found to potentially lower blood glucose (Garcia) [22] 1956 Jan Aron encourages Jean Sterne and Denise Duval to study guanidine-based glucose-lowering agents [6] 1957 Jean Sterne publishes use of metformin to treat diabetes [24] 1957-1959 Phenformin and buformin reported as treatments for diabetes [32,33,37,38] 1958 Metformin introduced to treat diabetes in the UK and other European countries [6] 1958 reported to reduce blood glucose in animals, and during the 1920s several mono-guanidine derivatives, notably galegine (isoamylene guanidine) and diguanidines, such as synthalin (two guanidines separated by a methylene chain; see Fig.…”

“…Also found to potentially lower blood glucose (Garcia) [22] 1956 Jan Aron encourages Jean Sterne and Denise Duval to study guanidine-based glucose-lowering agents [6] 1957 Jean Sterne publishes use of metformin to treat diabetes [24] 1957-1959 Phenformin and buformin reported as treatments for diabetes [32,33,37,38] 1958 Metformin introduced to treat diabetes in the UK and other European countries [6] 1958 reported to reduce blood glucose in animals, and during the 1920s several mono-guanidine derivatives, notably galegine (isoamylene guanidine) and diguanidines, such as synthalin (two guanidines separated by a methylene chain; see Fig. 2), were also shown to lower blood glucose in animals [6][7][8][9][10]. This led to the introduction of galegine and the more potent synthalin in diabetes treatment.…”

A Brief History of the Development of Diabetes Medications

“…7 In the early 20th century, the antihyperglycemic moiety in this plant, guanidine, was isolated. Frank et al 8 synthesized a guanidine compound called Synthalin in Germany and used it to treat diabetes during the 1920s. 3 Homologs of guanidine (e.g., Synthalin) were used for a short period but were hepatotoxic, and the use of these compounds all but ended with the discovery and proliferation of insulin.…”

Familial Hypoglycemia Precipitated by Amino Acids

“…This effect must be distinguished from the toxic actions of the diamidines which cause hypoglycemia after initial hyperglycemia by depletion of liver glycogen stores (44,45). Since leucine is always present in the blood it may be partly responsible for the low fasting blood sugar levels of these patients.…”