Biguanide - Revision history

Fire at 10:03, 23 April 2024

2024-04-23T10:03:24Z

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 {{short description|Chemical compound}}
 {{Pathnav|medication|diabetes medication|frame=1}}
 {{chembox
 | Watchedfields = changed

Fire: Marked this version for translation

2024-04-23T09:53:55Z

Marked this version for translation

← Older revision		Revision as of 18:53, 23 April 2024
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	'''Biguanide''' ({{IPAc-en\|b\|aɪ\|ˈ\|g\|w\|ɒ\|n\|aɪ\|d}}) is the organic compound with the formula HN(C(NH)NH<sub>2</sub>)<sub>2</sub>. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to [[ammonia]] and [[urea]].		'''Biguanide''' ({{IPAc-en\|b\|aɪ\|ˈ\|g\|w\|ɒ\|n\|aɪ\|d}}) is the organic compound with the formula HN(C(NH)NH<sub>2</sub>)<sub>2</sub>. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to [[ammonia]] and [[urea]].

	~~==Synthesis==~~ <!--T:3-->		<!--T:3-->
			==Synthesis==
	Biguanide can be obtained from the reaction of [[dicyandiamide]] with [[ammonia]], via a [[pinner reaction\|Pinner]]-type process.		Biguanide can be obtained from the reaction of [[dicyandiamide]] with [[ammonia]], via a [[pinner reaction\|Pinner]]-type process.

Line 58:		Line 59:
	Biguanide was first synthesized by [[Bernhard Rathke]] in 1879.		Biguanide was first synthesized by [[Bernhard Rathke]] in 1879.

	~~==Biguanidine drugs==~~ <!--T:6-->		<!--T:6-->
			==Biguanidine drugs==
	A variety of [[derivative (chemistry)\|derivatives]] of biguanide are used as pharmaceutical drugs.		A variety of [[derivative (chemistry)\|derivatives]] of biguanide are used as pharmaceutical drugs.

	~~===Antihyperglycemic agents===~~ <!--T:7-->		<!--T:7-->
			===Antihyperglycemic agents===
	The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic [[drug]]s used for [[diabetes mellitus]] or [[prediabetes]] treatment.		The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic [[drug]]s used for [[diabetes mellitus]] or [[prediabetes]] treatment.

Line 77:		Line 80:
	</gallery>		</gallery>

	~~====History====~~ <!--T:10-->		<!--T:10-->
			====History====
	{{details\|metformin#History}}		{{details\|metformin#History}}
	''[[Galega officinalis]]'' (French lilac) was used in diabetes treatment for centuries. 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). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.		''[[Galega officinalis]]'' (French lilac) was used in diabetes treatment for centuries. 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). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.

	====Mechanism of action==== ~~<!--T:11-->~~		<!--T:11-->
			====Mechanism of action====
	The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.		The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.

Line 96:		Line 101:
	Biguanides have been shown to interact with copper, specifically in mitochondria, where they interfere with cell metabolism by chelating Copper in its 2+ oxidation state (Cu(II)).		Biguanides have been shown to interact with copper, specifically in mitochondria, where they interfere with cell metabolism by chelating Copper in its 2+ oxidation state (Cu(II)).

	====Side effects and toxicity==== ~~<!--T:16-->~~		<!--T:16-->
			====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 advanced [[chronic kidney disease]]. Kidney function 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.		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 advanced [[chronic kidney disease]]. Kidney function 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===~~ <!--T:17-->		<!--T:17-->
			===Antimalarial===
	During WWII a British team led by [[Frank Rose (chemist)\|Frank Rose]] discovered (see details there) that some biguanides are useful as [[antimalarial drug]]s. Much later it was demonstrated that they are prodrugs metabolised into active [[dihydrotriazine]] derivatives which, until recently, were believed to work by [[Dihydrofolate reductase inhibitor\|inhibiting]] [[dihydrofolate reductase]]. Examples include:		During WWII a British team led by [[Frank Rose (chemist)\|Frank Rose]] discovered (see details there) that some biguanides are useful as [[antimalarial drug]]s. Much later it was demonstrated that they are prodrugs metabolised into active [[dihydrotriazine]] derivatives which, until recently, were believed to work by [[Dihydrofolate reductase inhibitor\|inhibiting]] [[dihydrofolate reductase]]. Examples include:
	* [[Proguanil]] (>[[cycloguanil]])		* [[Proguanil]] (>[[cycloguanil]])
	* [[Chlorproguanil]]		* [[Chlorproguanil]]

	~~===Disinfectants===~~ <!--T:18-->		<!--T:18-->
			===Disinfectants===
	{{see also\|Bisbiguanide}}		{{see also\|Bisbiguanide}}
	The disinfectants [[chlorhexidine]], [[polyaminopropyl biguanide]] (PAPB), [[polihexanide]], and [[alexidine]] feature biguanide [[functional group]]s.		The disinfectants [[chlorhexidine]], [[polyaminopropyl biguanide]] (PAPB), [[polihexanide]], and [[alexidine]] feature biguanide [[functional group]]s.

Fire at 09:52, 23 April 2024

2024-04-23T09:52:53Z

← Older revision		Revision as of 18:52, 23 April 2024
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	<!--T:1-->		<!--T:1-->
	{{short description\|Chemical compound}}		{{short description\|Chemical compound}}
			{{Pathnav\|medication\|diabetes medication\|frame=1}}
	{{chembox		{{chembox
	\| Watchedfields = changed		\| Watchedfields = changed

Fire: Marked this version for translation

2024-03-12T08:12:57Z

Marked this version for translation

← Older revision		Revision as of 17:12, 12 March 2024
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	<languages />		<languages />
	<translate>		<translate>
			<!--T:1-->
	{{short description\|Chemical compound}}		{{short description\|Chemical compound}}
	{{chembox		{{chembox
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	}}		}}

			<!--T:2-->
	'''Biguanide''' ({{IPAc-en\|b\|aɪ\|ˈ\|g\|w\|ɒ\|n\|aɪ\|d}}) is the organic compound with the formula HN(C(NH)NH<sub>2</sub>)<sub>2</sub>. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to [[ammonia]] and [[urea]].		'''Biguanide''' ({{IPAc-en\|b\|aɪ\|ˈ\|g\|w\|ɒ\|n\|aɪ\|d}}) is the organic compound with the formula HN(C(NH)NH<sub>2</sub>)<sub>2</sub>. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to [[ammonia]] and [[urea]].

	==Synthesis==		==Synthesis== <!--T:3-->
	Biguanide can be obtained from the reaction of [[dicyandiamide]] with [[ammonia]], via a [[pinner reaction\|Pinner]]-type process.		Biguanide can be obtained from the reaction of [[dicyandiamide]] with [[ammonia]], via a [[pinner reaction\|Pinner]]-type process.

			<!--T:4-->
	:<math>\mathrm{C_2H_4N_4 + NH_3 \longrightarrow C_2H_7N_5}</math>		:<math>\mathrm{C_2H_4N_4 + NH_3 \longrightarrow C_2H_7N_5}</math>

			<!--T:5-->
	Biguanide was first synthesized by [[Bernhard Rathke]] in 1879.		Biguanide was first synthesized by [[Bernhard Rathke]] in 1879.

	==Biguanidine drugs==		==Biguanidine drugs== <!--T:6-->
	A variety of [[derivative (chemistry)\|derivatives]] of biguanide are used as pharmaceutical drugs.		A variety of [[derivative (chemistry)\|derivatives]] of biguanide are used as pharmaceutical drugs.

	===Antihyperglycemic agents===		===Antihyperglycemic agents=== <!--T:7-->
	The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic [[drug]]s used for [[diabetes mellitus]] or [[prediabetes]] treatment.		The term "biguanidine" often refers specifically to a class of drugs that function as oral antihyperglycemic [[drug]]s used for [[diabetes mellitus]] or [[prediabetes]] treatment.

			<!--T:8-->
	Examples include:		Examples include:
	* [[Metformin]] - widely used in treatment of [[diabetes mellitus type 2]]		* [[Metformin]] - widely used in treatment of [[diabetes mellitus type 2]]
Line 64:		Line 69:
	* [[Buformin]] - withdrawn from the market due to toxic effects		* [[Buformin]] - withdrawn from the market due to toxic effects

			<!--T:9-->
	<gallery caption="bioactive biguanidines" widths="180px" heights="120px" perrow="3">		<gallery caption="bioactive biguanidines" widths="180px" heights="120px" perrow="3">
	File:Metformin.svg\|[[Metformin]], could be referred to as asymmetric dimethylbiguanidine		File:Metformin.svg\|[[Metformin]], could be referred to as asymmetric dimethylbiguanidine
Line 70:		Line 76:
	</gallery>		</gallery>

	====History====		====History==== <!--T:10-->
	{{details\|metformin#History}}		{{details\|metformin#History}}
	''[[Galega officinalis]]'' (French lilac) was used in diabetes treatment for centuries. 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). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.		''[[Galega officinalis]]'' (French lilac) was used in diabetes treatment for centuries. 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). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.

	====Mechanism of action====		====Mechanism of action==== <!--T:11-->
	The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.		The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.

			<!--T:12-->
	Biguanides do not affect the output of insulin, unlike other [[hypoglycemic agent]]s such as [[sulfonylurea]]s and [[meglitinide]]s. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.		Biguanides do not affect the output of insulin, unlike other [[hypoglycemic agent]]s such as [[sulfonylurea]]s and [[meglitinide]]s. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.

			<!--T:13-->
	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.		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.

			<!--T:14-->
	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 bloodstream, and there again reducing the level of glucose in the plasma.		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 bloodstream, and there again reducing the level of glucose in the plasma.

			<!--T:15-->
	Biguanides have been shown to interact with copper, specifically in mitochondria, where they interfere with cell metabolism by chelating Copper in its 2+ oxidation state (Cu(II)).		Biguanides have been shown to interact with copper, specifically in mitochondria, where they interfere with cell metabolism by chelating Copper in its 2+ oxidation state (Cu(II)).

	====Side effects and toxicity====		====Side effects and toxicity==== <!--T:16-->
	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 advanced [[chronic kidney disease]]. Kidney function 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.		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 advanced [[chronic kidney disease]]. Kidney function 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===		===Antimalarial=== <!--T:17-->
	During WWII a British team led by [[Frank Rose (chemist)\|Frank Rose]] discovered (see details there) that some biguanides are useful as [[antimalarial drug]]s. Much later it was demonstrated that they are prodrugs metabolised into active [[dihydrotriazine]] derivatives which, until recently, were believed to work by [[Dihydrofolate reductase inhibitor\|inhibiting]] [[dihydrofolate reductase]]. Examples include:		During WWII a British team led by [[Frank Rose (chemist)\|Frank Rose]] discovered (see details there) that some biguanides are useful as [[antimalarial drug]]s. Much later it was demonstrated that they are prodrugs metabolised into active [[dihydrotriazine]] derivatives which, until recently, were believed to work by [[Dihydrofolate reductase inhibitor\|inhibiting]] [[dihydrofolate reductase]]. Examples include:
	* [[Proguanil]] (>[[cycloguanil]])		* [[Proguanil]] (>[[cycloguanil]])
	* [[Chlorproguanil]]		* [[Chlorproguanil]]

	===Disinfectants===		===Disinfectants=== <!--T:18-->
	{{see also\|Bisbiguanide}}		{{see also\|Bisbiguanide}}
	The disinfectants [[chlorhexidine]], [[polyaminopropyl biguanide]] (PAPB), [[polihexanide]], and [[alexidine]] feature biguanide [[functional group]]s.		The disinfectants [[chlorhexidine]], [[polyaminopropyl biguanide]] (PAPB), [[polihexanide]], and [[alexidine]] feature biguanide [[functional group]]s.

			<!--T:19-->
	{{oral hypoglycemics}}		{{oral hypoglycemics}}
	{{antimalarials}}		{{antimalarials}}

			<!--T:20-->
	{{二次利用\|date=13 January 2024}}		{{二次利用\|date=13 January 2024}}
	[[Category:Biguanides\| ]]		[[Category:Biguanides\| ]]

Fire at 08:12, 12 March 2024

2024-03-12T08:12:45Z

← Older revision		Revision as of 17:12, 12 March 2024
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			<languages />
			<translate>
	{{short description\|Chemical compound}}		{{short description\|Chemical compound}}
	{{chembox		{{chembox
Line 75:		Line 77:
	The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.		The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.

	Biguanides do not affect the output of insulin, unlike other [[hypoglycemic agent]]s such as [[sulfonylurea]]s and [[meglitinide]]s. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.~~{{cn\|date=January 2024}}~~		Biguanides do not affect the output of insulin, unlike other [[hypoglycemic agent]]s such as [[sulfonylurea]]s and [[meglitinide]]s. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.

	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.~~{{cn\|date=January 2024}}~~		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 bloodstream, and there again reducing the level of glucose in the plasma.		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 bloodstream, and there again reducing the level of glucose in the plasma.
Line 102:		Line 104:
	[[Category:Guanidines]]		[[Category:Guanidines]]
	[[Category:Substances discovered in the 19th century]]		[[Category:Substances discovered in the 19th century]]
			</translate>

Fire: Created page with "{{short description|Chemical compound}} {{chembox | Watchedfields = changed | verifiedrevid = 444387711 | ImageFile = Biguanide.svg | ImageFile_Ref = {{chemboximage|correct|??}} | ImageSize = 160 | ImageName = Skeletal formula of biguanide | ImageFile1 = Biguanide-from-xtal-3D-bs-17.png | ImageFile1_Ref = {{chemboximage|correct|??}} | ImageSize1 = 160 | ImageName1 = Ball and stick model of biguanide | PIN = Imidodicarbonimidic diamide |Section1={{Chembox Identifiers | CA..."

2024-03-12T07:51:21Z

Created page with "{{short description|Chemical compound}} {{chembox | Watchedfields = changed | verifiedrevid = 444387711 | ImageFile = Biguanide.svg | ImageFile_Ref = {{chemboximage|correct|??}} | ImageSize = 160 | ImageName = Skeletal formula of biguanide | ImageFile1 = Biguanide-from-xtal-3D-bs-17.png | ImageFile1_Ref = {{chemboximage|correct|??}} | ImageSize1 = 160 | ImageName1 = Ball and stick model of biguanide | PIN = Imidodicarbonimidic diamide |Section1={{Chembox Identifiers | CA..."

New page

{{short description|Chemical compound}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 444387711
| ImageFile = Biguanide.svg
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageSize = 160
| ImageName = Skeletal formula of biguanide
| ImageFile1 = Biguanide-from-xtal-3D-bs-17.png
| ImageFile1_Ref = {{chemboximage|correct|??}}
| ImageSize1 = 160
| ImageName1 = Ball and stick model of biguanide
| PIN = Imidodicarbonimidic diamide
|Section1={{Chembox Identifiers
| CASNo = 56-03-1
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = FB4Q52I9K2
| PubChem = 5939
| ChemSpiderID = 5726
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| EINECS = 200-251-8
| KEGG = C07672
| KEGG_Ref = {{keggcite|correct|kegg}}
| ChEBI = 3095
| ChEBI_Ref = {{ebicite|correct|EBI}}
| Beilstein = 507183
| Gmelin = 240093
| SMILES = N=C(N)NC(=N)N
| StdInChI = 1S/C2H7N5/c3-1(4)7-2(5)6/h(H7,3,4,5,6,7)
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XNCOSPRUTUOJCJ-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
}}
|Section2={{Chembox Properties
| C=2 | H=7 | N=5
| pKa = 3.07, 13.25
}}
|Section3={{Chembox Related
| OtherCompounds =
}}
}}

'''Biguanide''' ({{IPAc-en|b|aɪ|ˈ|g|w|ɒ|n|aɪ|d}}) is the organic compound with the formula HN(C(NH)NH<sub>2</sub>)<sub>2</sub>. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to [[ammonia]] and [[urea]].

==Synthesis==
Biguanide can be obtained from the reaction of [[dicyandiamide]] with [[ammonia]], via a [[pinner reaction|Pinner]]-type process.

:<math>\mathrm{C_2H_4N_4 + NH_3 \longrightarrow C_2H_7N_5}</math>

Biguanide was first synthesized by [[Bernhard Rathke]] in 1879.

==Biguanidine drugs==
A variety of [[derivative (chemistry)|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 [[drug]]s used for [[diabetes mellitus]] or [[prediabetes]] treatment.

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

<gallery caption="bioactive biguanidines" widths="180px" heights="120px" perrow="3">
File:Metformin.svg|[[Metformin]], could be referred to as asymmetric dimethylbiguanidine
File:Buformin.svg|[[Buformin]]. A [[butyl]] derivative of biguanidine.
File:Phenformin.svg|[[Phenformin]]. A phenethylated biguanidine.
</gallery>

====History====
{{details|metformin#History}}
''[[Galega officinalis]]'' (French lilac) was used in diabetes treatment for centuries. 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). Metformin has a much better safety profile, and it is the principal biguanide drug used in pharmacotherapy worldwide.

====Mechanism of action====
The [[mechanism of action]] of biguanides is not fully understood, and many mechanisms have been proposed for metformin.

Biguanides do not affect the output of insulin, unlike other [[hypoglycemic agent]]s such as [[sulfonylurea]]s and [[meglitinide]]s. Therefore, they are effective in Type 2 diabetics; and in Type 1 diabetes when used in conjunction with insulin therapy.{{cn|date=January 2024}}

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.{{cn|date=January 2024}}

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 bloodstream, and there again reducing the level of glucose in the plasma.

Biguanides have been shown to interact with copper, specifically in mitochondria, where they interfere with cell metabolism by chelating Copper in its 2+ oxidation state (Cu(II)).

====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 advanced [[chronic kidney disease]]. Kidney function 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===
During WWII a British team led by [[Frank Rose (chemist)|Frank Rose]] discovered (see details there) that some biguanides are useful as [[antimalarial drug]]s. Much later it was demonstrated that they are prodrugs metabolised into active [[dihydrotriazine]] derivatives which, until recently, were believed to work by [[Dihydrofolate reductase inhibitor|inhibiting]] [[dihydrofolate reductase]]. Examples include:
* [[Proguanil]] (>[[cycloguanil]])
* [[Chlorproguanil]]

===Disinfectants===
{{see also|Bisbiguanide}}
The disinfectants [[chlorhexidine]], [[polyaminopropyl biguanide]] (PAPB), [[polihexanide]], and [[alexidine]] feature biguanide [[functional group]]s.

{{oral hypoglycemics}}
{{antimalarials}}

{{二次利用|date=13 January 2024}}
[[Category:Biguanides| ]]
[[Category:Guanidines]]
[[Category:Substances discovered in the 19th century]]