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Biguanide is the organic compound with the formula HN(C(NH)NH₂)₂. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea.^[1]

Biguanidine drugs

A variety of derivatives of biguanide are used as pharmaceutical drugs.

Antihyperglycemic agents

The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic drugs used for diabetes mellitus or prediabetes treatment.^[2]

Examples include:

Metformin - widely used in treatment of diabetes mellitus type 2
Phenformin - withdrawn from the market in most countries due to toxic effects
Buformin - withdrawn from the market due to toxic effects

bioactive biguanidines
Metformin, an "unsym"-dimethylbiguanidine
Buformin. A butyl derivative of biguanidine.
Phenformin. A phenethylated biguanidine.

History

Galega officinalis (French lilac) was used in diabetes treatment for centuries.^{[citation needed]} In the 1920s, guanidine compounds were discovered in Galega extracts. Animal studies showed that these compounds lowered blood glucose levels. Some less toxic derivatives, synthalin A and synthalin B, were used for diabetes treatment, but after the discovery of insulin, their use declined. Biguanides were reintroduced into Type 2 diabetes treatment in the late 1950s. Initially phenformin was widely used, but its potential for sometimes fatal lactic acidosis resulted in its withdrawal from most pharmacopeias (in the U.S. in 1978).^[3] Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.

Mechanistic aspects

Biguanides do not affect the output of insulin, unlike other hypoglycemic agents such as sulfonylureas and meglitinides. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.

The mechanism of action of biguanides is not fully understood. Mainly used in Type II Diabetes, metformin is considered to increase insulin sensitivity in vivo, resulting in reduced plasma glucose concentrations, increased glucose uptake, and decreased gluconeogenesis.

However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reduce gluconeogenesis in the liver, and, as a result, reduce the level of glucose in the blood. Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and there again reducing the level of glucose in the plasma.

Side effects and toxicity

The most common side effect is diarrhea and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is lactic acidosis, therefore metformin is contraindicated in renal insufficiency. Renal functions should be assessed before starting metformin. Phenformin and buformin are more prone to cause acidosis than metformin; therefore they have been practically replaced by it. However, when metformin is combined with other drugs (combination therapy), hypoglycemia and other side effects are possible.

Antimalarial

Some biguanides are also used as antimalarial drugs. Examples include:

Proguanil
Chlorproguanil

Disinfectants

The disinfectants chlorhexidine, polyaminopropyl biguanide (PAPB), polihexanide, and alexidine feature biguanide functional groups.

References

^ Thomas Güthner, Bernd Mertschenk and Bernd Schulz "Guanidine and Derivatives" in Ullmann's Encyclopedia of Industrial Chemistry, 2006, Wiley-VCH, Weinheim. doi:10.1002/14356007.a12_545.pub2
^ Rang; et al. (2003). Pharmacology (5th ed.). p. 388.
^ Tonascia, Susan; Meinert, Curtis L. (1986). Clinical trials: design, conduct, and analysis. Oxford [Oxfordshire]: Oxford University Press. pp. 53–54, 59. ISBN 0-19-503568-2.

UpToDate Contents

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1. 成人の2型糖尿病治療におけるメトホルミン metformin in the treatment of adults with type 2 diabetes mellitus
2. メトホルミン中毒 metformin poisoning
3. 糖尿病の治療におけるチアゾリジン thiazolidinediones in the treatment of diabetes mellitus
4. 乳酸アシドーシスの原因 causes of lactic acidosis
5. 成人の2型糖尿病における血糖の初期マネージメント initial management of blood glucose in adults with type 2 diabetes mellitus

English Journal

Biguanide related compounds in traditional antidiabetic functional foods.

Perla V, Jayanty SS.SourceSan Luis Valley Research Center, Department of Horticulture and Landscape Architecture, Colorado State University, 0249 East County Road 9N, Center, CO 81125, USA. venu.perla@colostate.edu
Food chemistry.Food Chem.2013 Jun 1;138(2-3):1574-80. doi: 10.1016/j.foodchem.2012.09.125. Epub 2012 Nov 23.
Biguanides such as metformin are widely used worldwide for the treatment of type-2 diabetes. The identification of guanidine and related compounds in French lilac plant (Galega officinalis L.) led to the development of biguanides. Despite of their plant origin, biguanides have not been reported in p
PMID 23411283

Increased peritoneal dialysis exit site infections using topical antiseptic polyhexamethylene biguanide compared to mupirocin: results of a safety interim analysis of an open-label prospective randomized study.

Findlay A, Serrano C, Punzalan S, Fan SL.SourceDepartment of Renal Medicine and Transplantation, Barts Health NHS Trust, London, United Kingdom.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 May;57(5):2026-8. doi: 10.1128/AAC.02079-12. Epub 2013 Feb 12.
Prophylactic mupirocin for peritoneal catheter exit sites reduces exit site infection (ESI) risk but engenders antibiotic resistance. We present early interim safety analysis of an open-label randomized study comparing polyhexamethylene biguanide (PHMB) and mupirocin. A total of 106 patients randomi
PMID 23403425

Japanese Journal

Tokushima Hypertension・Diabetes Study 2011 : Current status of hypertension and diabetes treatment in Tokushima

西内健,長瀬教夫,小松まち子
四国医学雑誌 = Shikoku acta medica 68(3・4), 111-118, 2012-08-25
… Frequency of use of biguanide increasedcompared with２００４. …
NAID 40019424313

心血管イベント予防 : 再評価されるビグアナイド : メトホルミン (特集インスリン抵抗性と心血管疾患)

渡邉隆宏,田村好史,綿田裕孝
循環器内科 71(5), 453-459, 2012-05
NAID 40019343168

Related Pictures

★リンクテーブル★

リンク元	「ビグアナイド系薬物」「メトホルミン」
拡張検索	「polyhexamethylene biguanide」「phenylbiguanide」「hypoglycemic of biguanide derivative」
関連記事	「biguanides」

「ビグアナイド系薬物」

Biguanide
Identifiers
CAS Registry Number	56-03-1
Beilstein Reference	507183
ChEBI	CHEBI:3095
ChemSpider	5726
EC number	200-251-8
Gmelin Reference	240093
	InChI InChI=1S/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7) ; Key: XNCOSPRUTUOJCJ-UHFFFAOYSA-N ;
Jmol-3D images	Image; Image
KEGG	C07672
PubChem	5939
	SMILES [nH]:c(:[nH2]):[nH]:c(:[nH]):[nH2] ; NC(=N)NC(N)=N ;
Properties
Chemical formula	C2H7N5
Molar mass	101.11 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

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英: biguanide,(総称)biguanides, hypoglycemic of biguanide derivative
関: 糖尿病治療薬、薬理学