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Biguanide (/baɪˈɡwɒnaɪd/) 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Phenformin - withdrawn from the market in most countries due to toxic effects
Buformin - withdrawn from the market due to toxic effects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, anassymetric dimethylbiguanidine
Buformin. A butyl derivative of biguanidine.
Phenformin. A phenethylated biguanidine.

History

Galega officinalis (French lilac) was used in diabetes treatment for centuries.^[3] 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).^[4] 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, and many mechanisms have been proposed for metformin.

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.^[5]

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.
^ Witters L. The blooming of the French lilac. J Clin Invest. 2001;108(8):1105–7. doi:10.1172/JCI14178. PMID 11602616. PMC 209536.
^ 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.
^ Tanzer JM, Slee AM, Kamay BA (1977). "Structural requirements of guanide, biguanide, and bisbiguanide agents for antiplaque activity". Antimicrob. Agents Chemother. 12 (6): 721–9. PMC 430011 . PMID 931371. doi:10.1128/aac.12.6.721.

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. 乳酸アシドーシスの原因 causes of lactic acidosis
4. 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
5. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus

English Journal

Risk of Cause-Specific Death in Individuals with Cancer-Modifying Role Diabetes, Statins and Metformin.

Haukka J1, Niskanen L2, Auvinen A3.
International journal of cancer.Int J Cancer.2017 Dec 15;141(12):2437-2449. doi: 10.1002/ijc.31016. Epub 2017 Sep 4.
PMID 28840596

Metformin attenuates albumin-induced alterations in renal tubular cells in vitro.

Allouch S1, Munusamy S1.
Journal of cellular physiology.J Cell Physiol.2017 Dec;232(12):3652-3663. doi: 10.1002/jcp.25838. Epub 2017 Apr 13.
PMID 28158902

Management of Diabetes in Children and Adolescents.

Levesque C1.
The Nursing clinics of North America.Nurs Clin North Am.2017 Dec;52(4):589-603. doi: 10.1016/j.cnur.2017.07.008. Epub 2017 Oct 5.
PMID 29080580

Japanese Journal

へき地医療機関における糖尿病診療の横断研究:HbA1c値, 使用薬剤の割合, 若手医師が診療で感じる困難さ

中嶋裕,福田吉治,原田昌範,中森芳宜
An Official Journal of the Japan Primary Care Association 35(3), 204-208, 2012
要旨目的 : へき地医療機関にて糖尿病患者におけるHbA1c値, 使用薬剤割合, 若手医師が診療で感じる困難さを明らかにする. 方法 : デザインは横断研究, 調査期間は2011年5月23日∼2011年6月17日, 対象施設は山口県のへき地医療機関, 対象者は糖尿病治療薬内服中の患者, 調査参加医師は対象施設に勤務する糖尿病非専門医, 診療情報は診療録から抽出, 医師へは …
NAID 130001935436

2型糖尿病の血糖降下薬のエビデンス

佐倉宏,岩本安彦
東京女子医科大学雑誌 81(E2), E89-E93, 2011-03-31
2型糖尿病の治療の基本は食事・運動療法であるが、血糖コントロールが十分に改善しない場合は、スルホニル尿素薬、ビグアナイド薬、α-グルコシダーゼ阻害薬、チアゾリジン薬、速効型インスリン分泌促進薬、DPP-4阻害薬の6系統のいずれかの経口血糖降下薬を用いた治療が開始されることが多い。作用機序の観点からは、インスリン抵抗性改善系のビグアナイド薬とチアゾリジン薬、インスリン分泌促進系のスルホニル尿素薬、速 …
NAID 110008441450

糖尿病が主体のメタボリックシンドロームの薬物療法ビグアナイド系薬 (メタボリックシンドローム(第2版)--基礎・臨床の最新知見) -- (予防・管理・治療)

高橋友乃,小田原雅人
日本臨床 69(-), 632-635, 2011-01-00
NAID 40018269714

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関連記事	「biguanide」

「biguanide」

Biguanide
Identifiers
CAS Number	56-03-1 ;
3D model (JSmol)	Interactive image; Interactive image;
Beilstein Reference	507183
ChEBI	CHEBI:3095 ;
ChemSpider	5726 ;
ECHA InfoCard	100.000.229
EC Number	200-251-8
Gmelin Reference	240093
KEGG	C07672 ;
PubChem CID	5939;
	InChI InChI=1S/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7) Key: XNCOSPRUTUOJCJ-UHFFFAOYSA-N ;
	SMILES [nH]:c(:[nH2]):[nH]:c(:[nH]):[nH2] ; NC(=N)NC(N)=N ;
Properties
Chemical formula	C2H7N5
Molar mass	101.11 g·mol−1
Acidity (pKa)	3.07, 13.25
	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

　　[★] ビグアナイド系薬物

[Ullmann-1] 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

[2] Rang; et al. (2003). Pharmacology (5th ed.). p. 388.

[Witters-3] Witters L. The blooming of the French lilac. J Clin Invest. 2001;108(8):1105–7. doi:10.1172/JCI14178. PMID 11602616. PMC 209536.

[Tonascia1986-4] 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.

[5] Tanzer JM, Slee AM, Kamay BA (1977). "Structural requirements of guanide, biguanide, and bisbiguanide agents for antiplaque activity". Antimicrob. Agents Chemother. 12 (6): 721–9. PMC 430011 . PMID 931371. doi:10.1128/aac.12.6.721.

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biguanides