Über Biguanide, II.: Die blutzucker‐senkende Wirkung der Biguanide

Slotta, K. H.; Tschesche, Rudolf

doi:10.1002/cber.19290620605

Cited by 67 publications

(34 citation statements)

References 11 publications

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“…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.…”

Section: Herbal Historymentioning

confidence: 99%

“…These developments provide the background for the synthesis of metformin (dimethylbiguanide) by Werner and Bell in 1922 [17]. Despite structural proximity to the glucose-lowering mono-and diguanidines, it was not until 1929 that metformin and other biguanides were reported to lower blood glucose levels in animals (rabbits and dogs) by Hesse and Taubmann and Slotta and Tschesche [18,19]. Importantly, biguanides were deemed to be less toxic than mono-and diguanidines and, of the various methyl biguanides tested, metformin exerted the least toxicity [19].…”

Section: From Galega To Biguanidesmentioning

confidence: 99%

“…Despite structural proximity to the glucose-lowering mono-and diguanidines, it was not until 1929 that metformin and other biguanides were reported to lower blood glucose levels in animals (rabbits and dogs) by Hesse and Taubmann and Slotta and Tschesche [18,19]. Importantly, biguanides were deemed to be less toxic than mono-and diguanidines and, of the various methyl biguanides tested, metformin exerted the least toxicity [19]. However, the real potential of these agents was underappreciated at the time because of the high doses required to achieve modest glucose-lowering effects in non-diabetic animals (compared with subsequent evidence in models of diabetes).…”

Section: From Galega To Biguanidesmentioning

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: Herbal Historymentioning

confidence: 99%

Section: From Galega To Biguanidesmentioning

confidence: 99%

Section: From Galega To Biguanidesmentioning

confidence: 99%

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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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“…15,16 These were non-toxic in animals but were not tested in humans. During the 1940s the antimalarial agent chloroguanidine hydrochloride was found to have a weak glucose-lowering effect, 17 and in 1949 a preparation of dimethylbiguanide (known as flumamine) was used against influenza in the Philippines.…”

Section: Early Biguanidesmentioning

confidence: 99%

Metformin: its botanical background

Bailey¹,

Day²

2004

Pract Diab Int

280

172

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This article traces the roots of the antihyperglycaemic biguanide metformin from the use of Galega officinalis (goat's rue or French lilac) as a herbal treatment for the symptoms of diabetes. G. officinalis was found to be rich in guanidine, a substance with blood glucose-lowering activity that formed the chemical basis of metformin. This insulin sensitising drug was introduced in 1957. Copyright Many biguanides and related guanidine derivatives have been examined as potential antidiabetic agents, 11,29 although much of this work pre-dates the availability of present models of insulin resistance. However, the multiple mechanisms of action and unique pharmacokinetic and pharmacodynamic properties of metformin confer a favourable risk-benefit ratio that has established metformin as a leading treatment for patients with type 2 diabetes. 30,31 Postscript of ironiesThere are several ironies about metformin. In our high-tech era of drug discovery and development this firstline treatment for type 2 diabetes is little removed from a herbal remedy of the middle ages. Despite its chemical simplicity and detailed investigation, metformin continues to evade a complete exposé of its cellular activity. While endless pharmacovigilance has monitored the safety profile of metformin, its natural ancestor, G. officinalis (known as Professor Weed in the USA) is a Class A Federal Noxious Weed in 35 states of America, and appears on the database of poisonous plants. 32 SHORT REPORTMetformin: its botanical background

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Über Biguanide, II.: Die blutzucker‐senkende Wirkung der Biguanide

Cited by 67 publications

References 11 publications

Metformin: historical overview

Metformin: historical overview

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

Metformin: its botanical background

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