Pharmacological Studies of a New Oral Hypoglycemic Drug

Ungar, Georges; Freedman, Louis; Shapiro, Seymour L.

doi:10.3181/00379727-95-23163

Cited by 152 publications

(60 citation statements)

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“…During the 1950s, other groups investigated guanidine derivatives, and the glucose-lowering properties of phenformin were rediscovered and published in 1957 by Ungar and colleagues (based in the USA) [32]. This was followed by reports .…”

Section: The Biguanide Opportunitymentioning

confidence: 99%

“…However, the mono-and diguanidine derivatives proved to be too toxic for continued clinical use, while phenformin and buformin were discontinued in most countries because of increased risk of lactic acidosis; only metformin is widely approved for use as a glucose-lowering agent in the management of type 2 diabetes of buformin's ability to reduce blood sugar levels in 1958, by A. Beringer (Germany) [32,33]. A vast selection of guanidine derivatives was then synthesised and evaluated, but enthusiasm was dampened by their lesser glucose-lowering efficacy in non-diabetic animals compared with agents that stimulate insulin secretion [34,35].…”

Section: The Biguanide Opportunitymentioning

confidence: 99%

“…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. 2), were also shown to lower blood glucose in animals [6][7][8][9][10].…”

Section: Herbal Historymentioning

confidence: 99%

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Metformin: historical overview

2017

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Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications.

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Section: The Biguanide Opportunitymentioning

confidence: 99%

Section: The Biguanide Opportunitymentioning

confidence: 99%

Section: Herbal Historymentioning

confidence: 99%

See 1 more Smart Citation

Metformin: historical overview

2017

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“…Guanidine compounds however, were too toxic for clinical use (Muller & Rheinwein, 1927). Through a series of testing and research, biguanides were then developed and shown to retain the antidiabetic effects of the guanidine like compounds yet safer to use clinically (Hesse & Taubmann, 1929;Mehnert & Seitz, 1958;Slotta & Tsesche, 1929;Sterne, 1957;Ungar et al, 1957).…”

Section: Efficacy Of Traditional Herbal Medicines Used To Treat Diabementioning

confidence: 99%

Mechanisms of Action of Traditional Herbal Medicines Used in the Management of Diabetes Mellitus: A Review of the Literature

Japhet¹,

Ngcobo²,

Gomo³

2017

Afr J Tradit Complement Altern Med

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Background: The prevalence of diabetes mellitus is increasing rapidly in both developed and developing countries. There are various conventional medicines used for the management of the disease, but there is also increased interest in the use of traditional herbal medicines. Although the concepts of illness and diseases in traditional medicine may differ from conventional medicine the outcomes are similar. The antihyperglycemic effects of various herbal medicines prescribed by traditional healers in the management of diabetes mellitus have been proven scientifically using several in-vitro and in-vivo models as well as clinical studies in humans. Materials and methods: Literature search was done in several databases. Firstly, the search was conducted using the key terms: diabetes mellitus and traditional medicine, diabetes mellitus and herbs, diabetes mellitus and plants, traditional concepts of health and sickness and diabetes mellitus. After identifying the herbs or plants used in diabetes a search was then conducted by name of herb and efficacy in management of diabetes mellitus. Results: This review highlights the similarities and differences in mechanisms of action of various traditional herbal medicines and conventional medicines. The major observation is that, herbal medicines often have multiple mechanisms of action ideally making them combination therapies. The review further highlights the need to develop an algorithm of a minimum battery of in-vitro and animal studies that can provide solid evidence of the potential of traditional medicines as anti-diabetic treatments. Conclusion: Traditional herbal medicines often have multiple phytoconstituents and hence multiple mechanisms of action ideally making them combination therapies.

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“…Though this compound proved too toxic for clinical use, alkyl diguanides were synthesized from it in the 1920s. In 1957, two independent research teams discovered that biguanidines, a third generation of guanidine derivatives, were efficacious as a new class of antidiabetic agents [11,12]. Derived from a prototypic molecule found in a plant with a long history of medicinal use, metformin exemplifies an efficacious drug the development of which was based on a use of a plant to treat diabetes.…”

Section: Plants Used To Treat Diabetesmentioning

confidence: 99%