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Metformin
Systematic (IUPAC) name
N,N-dimethylimidodicarbonimidic diamide
Identifiers
CAS number 657-24-9
ATC code A10BA02
A10BD02 (with sulfonylureas)
A10BD03 (with rosiglitazone)
A10BD05 (with pioglitazone)
A10BD07 (with sitagliptin)
A10BD08 (with vildagliptin)
PubChem 4091
DrugBank APRD01099
Chemical data
Formula C4H11N5 
Mol. mass 129.164 g/mol (free)
165.63 g/mol (HCl)
Synonyms 1,1-dimethylbiguanide
Pharmacokinetic data
Bioavailability 50 to 60% under fasting conditions
Metabolism None
Half life 6.2 hours
Excretion Active renal tubular excretion by OCT2
Therapeutic considerations
Licence data
Pregnancy cat. C(AU) B(US)
Legal status POM (UK) -only (US)
Routes Oral
 Yes check.svgY(what is this?)  (verify)
.Metformin (INN) (pronounced /mɛtˈfɔrmɪn/; originally sold as Glucophage) is an oral anti-diabetic drug.^ Metformin is an anti-diabetic .
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^ Categories : Anti-diabetic drugs .
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^ Metformin is an oral antihyperglycemic drug used in the management of type 2 diabetes.
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.It is the first-line drug of choice for the treatment of type 2 diabetes, particularly in overweight and obese people and those with normal kidney function.^ It is first-line pharmacotherapy in overweight and obese patients with type 2 diabetes.
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^ Metformin is currently recommended as an agent of choice for the treatment of type 2 diabetes, particularly in obese patients.
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^ What’s different is that ours is a first-line diabetes drug.
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[1][2][3] .Evidence is also mounting for its efficacy in gestational diabetes, although safety concerns still preclude its widespread use in this setting.^ Metformin may be useful in gestational diabetes.
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^ Although metformin is used for type 2 diabetes.
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^ This is a recommendation from the National Institute for Clinical Excellence (NICE) 2008 guidance on treating diabetes in pregnancy, which states that there is strong evidence for the safety and effectiveness of using metformin during pregnancy.
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.It is also used in the treatment of polycystic ovary syndrome and has been investigated for other diseases where insulin resistance may be an important factor.^ Acbay O, Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome?
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^ Metformin (Glucophage) for polycystic ovary syndrome .
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^ Insulin-lowering therapeutic modalities for polycystic ovary syndrome.
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.When prescribed appropriately, metformin causes few adverse effects—the most common is gastrointestinal upset—and, unlike many other anti-diabetic drugs, does not cause hypoglycemia if used alone.^ Do not use metformin for a condition for which it was not prescribed.
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^ Metformin is not used to treat type 1 diabetes (condition in which the body does not ...
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^ Unlike the other most-commonly prescribed oral diabetes drugs, the sulfonylureas , metformin monotherapy will not induce hypoglycemia .

.Lactic acidosis (a buildup of lactate in the blood) can be a serious concern in overdose and when it is prescribed to people with contraindications, but otherwise, there is no significant risk.^ The most significant risk associated with metformin is that of lactic acidosis.
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^ Are there other risk factors for lactic acidosis?
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^ Lactic acidosis is caused by a buildup of lactic acid in the blood.
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.Metformin helps reduce LDL cholesterol and triglyceride levels and is not associated with weight gain, and is the only anti-diabetic drug that has been conclusively shown to prevent the cardiovascular complications of diabetes.^ Metformin and a healthy weight also improve cholesterol levels.

^ Stopped Metformin - rapid weight gain help!
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^ Metformin is an anti-diabetic .
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.As of 2009, metformin is one of only two oral anti-diabetics in the World Health Organization Model List of Essential Medicines (the other being glibenclamide).^ Metformin is an anti-diabetic .
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^ Mary Metformin is an anti-diabetic drug.
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^ As of 2007, it is one of only two oral anti-diabetics in the World Health Organization Model List of Essential Medicines (the other being glibenclamide ).
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[4]
.First synthesized and found to reduce blood sugar in the 1920s, metformin was forgotten for the next two decades as research shifted to insulin and other anti-diabetic drugs.^ What is metformin effects on androgens and insulin with low blood sugar?
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^ He's taking Metformin too for blood sugar, so with the blood sugar problem ...
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^ Metformin is an anti-diabetic .
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.Interest in metformin was rekindled in the late 1940s after several reports that it could reduce blood sugar levels in people, and in 1957, French physician Jean Sterne published the first clinical trial of metformin as a treatment for diabetes.^ Metformin also reduced hemoglobin A1C levels, a blood measurement of glycosylation.
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^ It is used to control blood glucose (blood sugar) for people with type 2 diabetes.
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^ Overall, metformin reduces blood sugar levels both between and directly after meals.
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.It was introduced to the United Kingdom in 1958, Canada in 1972, and the United States in 1995. Metformin is now believed to be the most widely prescribed anti-diabetic drug in the world; in the United States alone, more than 40 million prescriptions were filled in 2008 for its generic formulations.^ Recently, more doctors are prescribing the drug metformin to help with this.
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^ Metformin is the most popular anti-diabetic drug in the United States and one of the most prescribed drugs overall, with nearly 35 million prescriptions filled in 2006 for generic metformin alone.

^ Metformin is a drug that is prescribed to treat type 2 diabetes.

[5][6]

Contents

History

.The biguanide class of anti-diabetic drugs, which also includes the withdrawn agents phenformin and buformin, originates from the French lilac (Galega officinalis), a plant used in folk medicine for several centuries.^ Metformin is an antidiabetic agent that belongs to a class of drugs called biguanides.
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^ Metformin is an antidiabetic agent that belongs to a class of drugs called biguanides .

^ Categories : Anti-diabetic drugs .
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[7]
.Metformin was first described in the scientific literature in 1922, by Emil Werner and James Bell, as a side product in the synthesis of N,N-dimethylguanidine.^ Metformin was first described in the scientific literature in 1957.
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^ DATA SYNTHESIS: Metformin is first-line pharmacotherapy in the treatment of overweight or obese patients with type 2 diabetes, with beneficial effects on weight in this population.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]

^ The optimal period of first-line metformin monotherapy for fertility is debatable given its theoretical safer side effect profile (fewer risks compared with clomiphene).
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[8] .In 1929, Slotta and Tschesche discovered its sugar-lowering action in rabbits, noting that it was the most potent of the biguanide analogs they studied.^ They lower blood sugar by: .
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^ However, it is important to note that most of the studies had low numbers of participants (only 4 studies had a sample size [n] > 50, 3 studies with n > 100).
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^ In addition, studies of people with Type 1 diabetes find that metformin will lower the amount of insulin they need to use.
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[9] .This result was completely forgotten as other guanidine analogs, such as the synthalins, took over, and were themselves soon overshadowed by insulin.^ There is also emerging support for the use of other insulin-sensitising agents, such as thiazolidenediones, 6 but that is beyond the scope of this review.
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^ Rosiglitazone may be used alone or in combination with other types of anti-diabetic drugs such as metformin or sulfonylureas as well as insulin.
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^ Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing's syndrome.
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[10]
.Interest in metformin, however, picked up at the end of the 1940s.^ Dec 13, 2009 12:10AM To: Andrea and others I remember going to the clinic to pick up the Metformin.
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^ I did try metformin about 1.5 years ago, however I gave up on it very quickly, and I was hardly eating.

^ Store METFORMIN at work on Friday and picked METFORMIN up in your blood sugar to drop to normal with oral treatments, but METFORMIN is causally marred in putsch with postscript.
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.In 1950, metformin, unlike some other similar compounds, was found not to decrease blood pressure and heart rate in animals.^ Unlike the other side effects from metformin .
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^ Metformin interacts with few other drugs, but a relevant interaction is its competitive inhibition for renal tubular secretion by cimetidine, resulting in decreased metformin renal clearance ( 5 ).
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^ Some dangers and problems associated with Metformin may be reduced by simply asking your doctor to lower the dosage or by switching to a similar medicine.
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[11] .That same year, a prominent Philippine physician, Eusebio Y. Garcia,[12] used metformin (he named it Fluamine) to treat influenza; he noted that the drug "lowered the blood sugar to minimum physiological limit" in treated patients and was non-toxic.^ How much does Metformin lower blood sugar concentrations?
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^ They lower blood sugar by: .
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^ He's taking Metformin too for blood sugar, so with the blood sugar problem ...
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Garcia also believed metformin to have bacteriostatic, antiviral, antimalarial, antipyretic and analgesic actions.[13] .In a series of articles in 1954, Polish pharmacologist Janusz Supniewski[14] was unable to confirm most of these effects, including lowered blood sugar; he did, however, observe some antiviral effects in humans.^ They lower blood sugar by: .
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^ Metformin lowers blood sugar levels by: .
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^ These actions lower the level of sugar in the blood.
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[15][16]
.While training at the Hôpital de la Pitié, French diabetologist Jean Sterne studied the antihyperglycemic properties of galegine, an alkaloid isolated from Galega officinalis, which is structurally related to metformin and had seen brief use as an anti-diabetic before the synthalins were developed.^ Before using Metformin : .
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^ Metformin is an anti-diabetic .
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^ Metformin is an oral antihyperglycemic drug used in the management of type 2 diabetes.
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[5] .Later, working at Laboratoires Aron in Paris, he was prompted by Garcia's report to re-investigate the blood sugar lowering activity of metformin and several biguanide analogs.^ How much does Metformin lower blood sugar concentrations?
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^ They lower blood sugar by: .
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^ He's taking Metformin too for blood sugar, so with the blood sugar problem ...
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Sterne was the first to try metformin on humans for the treatment of diabetes; he coined the name "Glucophage" (glucose eater) for the drug and published his results in 1957.[5][10]
.Metformin became available in the British National Formulary in 1958. It was sold in the UK by a small Aron subsidiary called Rona.^ Also, metformin is available as part of combination products with two different sulfonylureas (glyburide and glipizide), called Glucovance and Metaglip, respectively.
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^ A liquid version of metformin, called Riomet , is also available.

^ Long-acting metformin 1000 mg tablets are also available and are sold under the brand names of Fortamet and Glumetza .

[17]
.Broad interest in metformin was not rekindled until the withdrawal of the other biguanides in the 1970s.^ Glucophage, Fortamet, Riomet, Glumetza) Metformin is an anti-diabetic drug from the biguanide class (its other members are the withdrawn agents phenformin and buformin).
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^ Do not take ARROW - METFORMIN if you are allergic to medicines containing metformin or other biguanides, or any of the ingredients listed at the end of this leaflet.
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^ In the 1960s and early 1970s, other biguanides (phenformin and buformin) were available to treat type 2 diabetes.
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.Metformin was approved in Canada in 1972,[18] but did not receive approval by the U.S. Food and Drug Administration (FDA) for Type 2 diabetes until 1994.[19] Produced under license by Bristol-Myers Squibb, Glucophage was the first branded formulation of metformin to be marketed in the United States, beginning on March 3, 1995.[20] Generic formulations are now available in several countries, and metformin is believed to have become the most widely prescribed anti-diabetic drug in the world.^ Metformin (Generic Glucophage) is used to treat type 2 diabetes that is not controlled on diet alone.
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^ Metformin is the most popular anti-diabetic drug in the United States and one of the most prescribed drugs overall, with nearly 35 million prescriptions filled in 2006 for generic metformin alone.

^ But, I'm considering going with the brand Glucophage instead of doing the generic Metformin.
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[5]

Treatment of diabetes

.The main use for metformin is in the treatment of diabetes mellitus type 2, especially in overweight people.^ Metformin is not used to treat type 1 diabetes (condition in which the body does not ...
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^ Metformin can also be used to treat people with type 2 diabetes who need to take insulin.
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^ It is used to control blood glucose (blood sugar) for people with type 2 diabetes.
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.In this group, over 10 years of treatment, metformin reduced diabetes complications and overall mortality by about 30% when compared with insulin and sulfonylureas (glibenclamide and chlorpropamide) and by about 40% when compared with the group only given dietary advice.^ Diabetes, Type 2 : I was given metformin for borderline type 2 diabetes.
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^ A Trial in Progress: Gestational Diabetes: Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial).
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^ Fig 4 Metformin compared with placebo or no treatment—fasting insulin .
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[21] .This difference held in the patients who were followed for 5–10 years after the study.^ The study included 401 patients, average age 56, with type 2 diabetes and advanced systolic heart failure who were followed for 14 years in a heart-failure management program.
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^ However, on the basis of this new study, I think trying it again for patients who are stuck on an atypical antipsychotic may be warranted.
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^ In the recent 10 year follow-up of the UKPDS, however, treatment with insulin secretagogues or insulin reduced cardiovascular events and mortality in a combined group of non-obese and obese patients with type 2 diabetes.
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[22] .In addition, metformin had no effect on body weight: over the 10-year treatment period, the metformin group gained about 1 kg, the same as the dietary advice group, while the sulfonylureas group gained 3 kg, and the insulin group, 6 kg.^ There was no additive effect of metformin and insulin ( P > 0.2).
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^ Fig 4 Metformin compared with placebo or no treatment—fasting insulin .
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^ Unlike insulin, metformin exerts no effect on Abeta degradation.
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[21][23] .As metformin affords a similar level of blood sugar control to insulin and sulfonylureas, it appears to decrease mortality primarily through decreasing heart attacks, strokes and other cardiovascular complications.^ What is metformin effects on androgens and insulin with low blood sugar?
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^ Metformin Metformin is an oral diabetes medicine that helps control blood sugar levels.

^ Fortamet Metformin is an oral diabetes medicine that helps control blood sugar levels.

.Unlike the other most-commonly prescribed class of oral diabetes drugs, the sulfonylureas, metformin does not induce hypoglycemia when taken alone and used at recommended dosages.^ Metformin is not used to treat type 1 diabetes (condition in which the body does not ...
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^ Unlike the other most-commonly prescribed oral diabetes drugs, the sulfonylureas , metformin monotherapy will not induce hypoglycemia .

^ Metformin hydrochloride, USP is an oral antihyperglycemic drug used in the management of type 2 diabetes.
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[24][25] .Hypoglycemia during intense exercise has been documented, but is extremely rare.^ Hypoglycemia during intense exercise has been documented, but is extremely rare.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ When transferring from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.
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^ Side-effects of the drugs were "rare and mild", and he noted that any babies' hypoglycemia is preventable by using continuous insulin infusion during delivery.

[26] .It is also not associated with weight gain, and modestly reduces LDL and triglyceride levels.^ Metformin also modestly reduces LDL and triglyceride levels.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ As a serum creatinine levels over 80 years of age all exercise and weight gain associated with Glucophage.
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^ Hopefully it will help reduce my weight as well as my insulin levels.
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[24][25]
.Several epidemiological and case-controlled studies found that diabetics using metformin may have lower cancer risk in comparison to those using other sugar-lowering medications.^ But this increase in the use of metformin is not without risk.
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^ Metformin was started at risk for type 2 diabetics.
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^ It is used to control blood glucose (blood sugar) for people with type 2 diabetes.
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.The causes of this phenomenon are unclear, and the results require confirmation in controlled studies.^ The U.S. Food and Drug Administration (FDA) required large safety studies of metformin, the results of which demonstrated that the development of lactic acidosis as a result of metformin therapy is very rare.

^ Additional studies will be required to further elucidate precise mechanism(s) by which metformin-stimulated AMPK activation could result in inhibition of hepatic glucose production.
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

^ Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study.
  • Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial -- Lund et al. 339: b4324 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

[27]

Off-label use

.Metformin is also being used increasingly in polycystic ovary syndrome (PCOS),[28] non-alcoholic fatty liver disease (NAFLD)[29] and premature puberty,[30] three other diseases that feature insulin resistance; these indications are still considered experimental.^ Acbay O, Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome?
  • eMJA: Norman et al, Metformin and intervention in polycystic ovary syndrome 16 January 2010 3:50 UTC www.mja.com.au [Source type: Academic]

^ Metformin (Glucophage) for polycystic ovary syndrome .
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^ Insulin-lowering therapeutic modalities for polycystic ovary syndrome.
  • Metformin for PCOS & Pregnancy - Fertility Plus 16 January 2010 3:50 UTC www.fertilityplus.org [Source type: Academic]

.The benefit of metformin in NAFLD has not been extensively studied and may be only temporary;[31] although some randomized controlled trials have found significant improvement with its use, the evidence is still insufficient.^ Study Design A double-blind, placebo-controlled randomized design was used.
  • Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study -- Wu et al. 165 (3): 352 -- Am J Psychiatry 16 January 2010 3:50 UTC ajp.psychiatryonline.org [Source type: Academic]

^ The benefit of metformin in NAFLD has not been extensively studied and may be only temporary.
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^ Metformin/TZDs are used, but what about the evidence?
  • Metformin & glitazones: Do they really help PCOS patients? — The Journal of Family Practice 16 January 2010 3:50 UTC www.jfponline.com [Source type: Academic]

[32][33]

Prediabetes

.Metformin treatment of people at risk for type 2 diabetes may decrease their chances of developing the disease, although intensive physical exercise and dieting work significantly better for this purpose.^ Treatment is combined with a balanced diet and exercise.
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^ Metformin was started at risk for type 2 diabetics.
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^ Are there any prescription treatments for type 2 diabetes?
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.In a large U.S. study known as the Diabetes Prevention Program, participants were divided into groups and given either placebo, metformin, or lifestyle intervention, and followed for an average of three years.^ About 5 percent of the lifestyle intervention group developed diabetes each year during the study period, compared with 11 percent of those in the placebo group.

^ Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]
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^ Diabetes, Type 2 : I was given metformin for borderline type 2 diabetes.
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.The intensive program of lifestyle modifications included a 16-lesson training on dieting and exercise followed by monthly individualized sessions with the goals to decrease the body weight by 7% and engage in a physical activity for at least 150 minutes per week.^ The first group, called the lifestyle intervention group, received intensive training in diet, physical activity, and behavior modification.

^ Intensive lifestyle consisted of reduction of at least 7% of body weight, low-calorie and low-fat diet, and moderate physical activity at least 150 minutes weekly ...
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^ All subjects were instructed to follow their usual diet and physical activity.
  • Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome -- Palomba et al. 21 (2): 457 -- Human Reproduction 16 January 2010 3:50 UTC humrep.oxfordjournals.org [Source type: Academic]

.The incidence of diabetes was 58% lower in the lifestyle group and 31% lower in those given metformin.^ Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]
  • Journal of Clinical Investigation -- Pharmacogenetics of metformin response: a step in the path toward personalized medicine 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]
  • Metformin therapy and clinical uses -- Scarpello and Howlett 5 (3): 157 -- Diabetes and Vascular Disease Research 16 January 2010 3:50 UTC www.dvdres.com [Source type: Academic]

^ Diabetes, Type 2 : I was given metformin for borderline type 2 diabetes.
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^ Metformin has been proven in clinical trials to lower glucose levels amongst children between 10-16 years of age suffering from type 2 diabetes.
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.Among people under 44 years of age and those with a body mass index greater than 35, lifestyle modification was no more effective than metformin, and for those older than 60, metformin was no better than placebo in preventing diabetes.^ Metformin was effective for both men and women, but it was least effective in people aged 45 and older.

^ The potential of metformin for diabetes prevention - Diabetes Metab.
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^ Metformin was most effective in people 25 to 44 years old and in those with a body mass index of 35 or higher, meaning they were at least 60 pounds overweight.

[34] .After ten years, the incidence of diabetes was 34% lower in the group of participants given diet and exercise and 18% lower in those given metformin.^ It is used along with diet and exercise to control high blood sugar in individuals with type 2 diabetes .
  • Glyburide and Metformin - OrganizedWisdom Health 16 January 2010 3:50 UTC organizedwisdom.com [Source type: General]

^ Metformin has been proven in clinical trials to lower glucose levels amongst children between 10-16 years of age suffering from type 2 diabetes.
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^ Two significant factors were noted: 1) Those also using insulin and other anti-diabetic medications (without metformin) actually had a dramatic increase in pancreatic cancer risk (2.5 - 5 times the risk); 2) Exercising, controlling blood sugar, dieting and quitting smoking did not seem to improve the benefits of metformin.

[35] .It is unclear whether metformin slowed down the progression of pre-diabetes to diabetes (true preventive effect), or the decrease of diabetes in the treated population was simply due to its blood-lowering action (treatment effect).^ The potential of metformin for diabetes prevention - Diabetes Metab.
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^ Diabetic pre-coma (due to ketoacidosis in severe and inadequately treated diabetes).
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^ Metformin lowers blood sugar levels by: .
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[36]

Polycystic ovary syndrome

.Antidiabetic therapy has been proposed as a treatment for polycystic ovary syndrome, a condition frequently associated with insulin resistance, since the late 1980s.^ Acbay O, Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome?
  • eMJA: Norman et al, Metformin and intervention in polycystic ovary syndrome 16 January 2010 3:50 UTC www.mja.com.au [Source type: Academic]

^ Metformin (Glucophage) for polycystic ovary syndrome .
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^ Insulin-lowering therapeutic modalities for polycystic ovary syndrome.
  • Metformin for PCOS & Pregnancy - Fertility Plus 16 January 2010 3:50 UTC www.fertilityplus.org [Source type: Academic]

[37] .The use of metformin in PCOS was first reported in 1994, in a small study conducted at the University of the Andes, Venezuela.^ Published studies on metformin in PCOS .
  • eMJA: Norman et al, Metformin and intervention in polycystic ovary syndrome 16 January 2010 3:50 UTC www.mja.com.au [Source type: Academic]

^ This trial did not show evidence of benefit for metformin compared with clomifene in our analysis when odds ratios were used, although it did in the original report.
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Historically, the first study on metformin in PCOS to be published was an uncontrolled study (10) in 1994, where 26 obese women with PCOS were treated with metformin at a dose of 500 mg three times daily for 8 weeks.
  • ROLE OF METFORMIN IN THE TREATMENT OF INFERTILITY IN PCOS 16 January 2010 3:50 UTC www.pcos.i8.com [Source type: Academic]

[38][39] .The United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin for anovulation and infertility when other therapy has failed to produce results.^ Metformin failed to work for 27 of these women and were given other therapy.

^ Although metformin is not licensed for use in PCOS , the United Kingdom's ...
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^ Results of the United Kingdom Prospective Diabetes Study showed that metformin: .
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[40] .However, two large clinical studies completed in 2006–2007 returned mostly negative results, with metformin being no better than placebo and metformin-clomifene combination no better than clomifene alone.^ Fig 2 Metformin combined with clomifene compared with clomifene alone—ovulation rate .
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Twenty-two women completed the study.
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^ There was no clinically significant change with metformin in any of the parameters we studied .
  • Metformin & glitazones: Do they really help PCOS patients? — The Journal of Family Practice 16 January 2010 3:50 UTC www.jfponline.com [Source type: Academic]

[41][42] .Reflecting this, subsequent reviews noted that large randomized control trials have in general not shown the promise suggested by the early small studies.^ A randomized, controlled trial.
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  • Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial -- Lund et al. 339: b4324 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Although antioxidant treatments can show benefits in animal models of diabetes, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating complications.
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^ Publication Types: Clinical trial Randomized controlled trial .
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.U.K. and international clinical practice guidelines do not recommend metformin as a first-line treatment[43] or do not recommend it at all, except for women with glucose intolerance.^ Two women ovulated after metformin treatment.
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  • Metformin treatment reduces ovarian cytochrome P-450c17{alpha} response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome -- la Marca et al. 15 (1): 21 -- Human Reproduction 16 January 2010 3:50 UTC humrep.oxfordjournals.org [Source type: Academic]

^ Context According to package inserts, metformin is contraindicated in diabetic patients receiving drug treatment for heart failure therapy, and thiazolidinediones are not recommended in diabetic patients with symptoms of advanced heart failure.
  • JAMA -- Abstract: Metformin and Thiazolidinedione Use in Medicare Patients With Heart Failure, July 2, 2003, Masoudi et al. 290 (1): 81 16 January 2010 3:50 UTC jama.ama-assn.org [Source type: Academic]

^ There is no evidence to support the routine use of either metformin or a TZD as first-line therapy for the treatment of PCOS, based on a meta-analysis of randomized controlled clinical trials (strength of recommendation [SOR]: C ).
  • Metformin & glitazones: Do they really help PCOS patients? — The Journal of Family Practice 16 January 2010 3:50 UTC www.jfponline.com [Source type: Academic]

[44] .The guidelines suggest clomiphene as the first medication option and emphasize lifestyle modification independently from the drug treatment.^ Obesity, polycystic ovary syndrome, infertility treatment: Lifestyle modification is paramount.
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ These treatment effects were achieved despite similar glycaemic regulation with both drugs and were independent of known CVD. .
  • Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes -- Lund et al. 158 (5): 631 -- European Journal of Endocrinology 16 January 2010 3:50 UTC www.eje-online.org [Source type: Academic]

^ Compared with metformin, also known as Glucophage, single-drug treatment with first- and second-generation sulfonylureas was associated with up to a 61% increased risk for death.
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.In a dissenting opinion, a systematic review of four head-to-head comparative trials of metformin and clomifene found them equally effective for infertility.^ Comment A systematic review and meta-analysis of data from controlled trials found that pre-conception use of metformin for polycystic ovary syndrome was not associated with any significant increase in risk of spontaneous ...

^ This trial did not show evidence of benefit for metformin compared with clomifene in our analysis when odds ratios were used, although it did in the original report.
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Whether metformin has equal potency on potentially important CVD biomarkers when compared with an insulin secretagogue in non-obese patients with T2DM is unknown.
  • Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes -- Lund et al. 158 (5): 631 -- European Journal of Endocrinology 16 January 2010 3:50 UTC www.eje-online.org [Source type: Academic]

[45] .A BMJ editorial noted that four positive studies of metformin were in patients who did not respond to clomifene, while the population in the negative studies was drug-naive or uncontrolled for the previous treatment.^ Context According to package inserts, metformin is contraindicated in diabetic patients receiving drug treatment for heart failure therapy, and thiazolidinediones are not recommended in diabetic patients with symptoms of advanced heart failure.
  • JAMA -- Abstract: Metformin and Thiazolidinedione Use in Medicare Patients With Heart Failure, July 2, 2003, Masoudi et al. 290 (1): 81 16 January 2010 3:50 UTC jama.ama-assn.org [Source type: Academic]

^ January 2010 23:57 A new study has shown that metformin, a drug often used in the treatment of diabetes mellitus, is safe for use in treating patients who have both diabetes and advanced heart failure.

^ This trial did not show evidence of benefit for metformin compared with clomifene in our analysis when odds ratios were used, although it did in the original report.
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

.The editorial suggested that metformin should be used as a second-line drug if clomifene treatment fails.^ How should I use Apo-Metformin?
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^ Metformin should not be used by women who: .
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^ How should Metformin be used?
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[46] .Another review recommended metformin unreservedly as a first-line treatment option because it has positive effects not only on anovulation but also on insulin resistance, hirsutism, and obesity often associated with PCOS.[47] A large Cochrane Collaboration review of 27 randomized clinical trials found that metformin improves ovulation and pregnancy rates, particularly when combined with clomifene, but is not associated with any increase in the number of live births.^ PCOS is very often associated with insulin resistance (IR) and hyperinsulinemia (hyper I).
  • Metformin for PCOS & Pregnancy - Fertility Plus 16 January 2010 3:50 UTC www.fertilityplus.org [Source type: Academic]

^ Fig 2 Metformin combined with clomifene compared with clomifene alone—ovulation rate .
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Fig 1 Metformin compared with placebo or no treatment—ovulation rate .
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

[48]
.The design of the negative trials may be one of the explanations for the contradictory results.^ Clinically meaningful results from this trial are questionable due to the open-label design and the lack of a placebo group.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]

.For example, using live birth rate instead of pregnancy as the end point may have biased some trials against metformin, which works slower than clomifene.^ Metformin users may be dismayed to find it not working like it used to.

^ Recently, a slow release form of metformin (metformin XR) given once a day, has become available in North America (currently not available in the UK) and its effectiveness is being evaluated in a multicenter-randomised trial comparing the effect of clomiphene, metformin and combined clomiphene and metformin o n live birth rates in women with PCOS .
  • ROLE OF METFORMIN IN THE TREATMENT OF INFERTILITY IN PCOS 16 January 2010 3:50 UTC www.pcos.i8.com [Source type: Academic]

^ The degree of mitochondrial inhibition by metformin may be less than that by the other biguanides, but the most important factor that accounts for metformin's relative safety is that, in contrast to phenformin, it does not require hepatic metabolism and instead is excreted unchanged by the kidney.
  • Metformin's contraindications: needed for now -- Fantus 173 (5): 505 -- Canadian Medical Association Journal 16 January 2010 3:50 UTC www.cmaj.ca [Source type: Academic]

[49] .Another explanation may be different efficacy of metformin in different populations of patients.^ Note that when you buy Metformin online internationally, there may be cosmetic differences such as color of pill, packaging, etc.
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^ The riskof lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin.
  • Metformin Hydrochloride (Tablet, Film Coated) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

^ DATA SYNTHESIS: Metformin is first-line pharmacotherapy in the treatment of overweight or obese patients with type 2 diabetes, with beneficial effects on weight in this population.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]

.The negative trials contained large percent of obese and previously untreated patients whose response to metformin may be weaker.^ Metformin was chosen if the patient was obese.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ Metformin is gastrointestinal upset can cause a decrease recent reports of randomized clinical trial of metformin on complications in patients below hydrate and swell.

^ The riskof lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin.
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[49]

Gestational diabetes

.Several observational studies and randomized controlled trials have found that metformin is as effective and safe as insulin for the management of gestational diabetes,[50][51][52] and a small case-control study has suggested that the children of women given metformin instead of insulin may be healthier in the neonatal period.^ Hemodialysis may be effective for the removal of metformin.

^ A Trial in Progress: Gestational Diabetes: Treatment with metformin compared with insulin (the Metformin in Gestational Diabetes [MiG] trial).
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Metformin controls diabetes but does not cure it.
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[53] .Nonetheless, several concerns have been raised regarding studies published thus far, and evidence on the long-term safety of metformin for both mother and child is still lacking.^ Published studies on metformin in PCOS .
  • eMJA: Norman et al, Metformin and intervention in polycystic ovary syndrome 16 January 2010 3:50 UTC www.mja.com.au [Source type: Academic]

^ So does the research on long-term safety and METFORMIN is needed.
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^ Lactic acidosis is a rare but serious side effect in diabetes, but has not been described in PCOS. Given the present lack of long-term safety data and demonstrable efficacy in a large number of patients, we recommend that metformin use be supervised by an endocrinologist or physician with expertise in the area.
  • eMJA: Norman et al, Metformin and intervention in polycystic ovary syndrome 16 January 2010 3:50 UTC www.mja.com.au [Source type: Academic]

[54]

Investigational findings

.A large case-control study conducted at M.D. Anderson Cancer Center has suggested that metformin may protect against pancreatic cancer.^ Sulphonylureas and cancer: a case-control study.
  • Metformin in the treatment of diabetes mellitus 16 January 2010 3:50 UTC www.uptodate.com [Source type: Academic]

^ In women with gestational diabetes, glyburide is more effective than metformin for achieving glycemic control, according to a study in the January issue of Obstetrics & Gynecology .
  • Metformin (generic), Glucophage News - Topix 16 January 2010 3:50 UTC www.topix.com [Source type: General]

^ These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment.
  • Metformin Is an AMP Kinase-Dependent Growth Inhibitor for Breast Cancer Cells -- Zakikhani et al. 66 (21): 10269 -- Cancer Research 16 January 2010 3:50 UTC cancerres.aacrjournals.org [Source type: Academic]

.The risk of pancreatic cancer in study participants who took metformin was found to be 62% lower than in participants who had never taken it, whereas participants who had used insulin or secretagogues (such as the sulfonylureas) were found to have a 5-fold and 2.5-fold higher risk of pancreatic cancer, respectively, compared to participants that had been treated with neither.^ Metformin can also be used to treat people with type 2 diabetes who need to take insulin.
  • Health: Biguanides for type 2 diabetes; Biguanides do not cause low blood sugar ... 16 January 2010 3:50 UTC www.maimonidesmed.org [Source type: FILTERED WITH BAYES]
  • CIGNA - Biguanides for type 2 diabetes 16 January 2010 3:50 UTC www.cigna.com [Source type: FILTERED WITH BAYES]

^ Metformin should not be taken by anyone who: .
  • Apo-Metformin - Uses, Side Effects, Interactions - Drugs - Medbroadcast 16 January 2010 3:50 UTC www.medbroadcast.com [Source type: FILTERED WITH BAYES]

^ A 4 year population study of over 1,800 participants (973 with pancreatic adenocarcinoma and 863 without) found that diabetics who were using metformin exhibited a 62% reduced risk of pancreatic cancer.

[55] .The study had several limitations, however, and the reason for this risk reduction is still unclear.^ In the United Kingdom Prospective Diabetes Study (UKPDS) a reduction of HbA 1c significantly decreased the risk for the development of microvascular complications in patients with type 2 diabetes (16).
  • Chapter 14. Oral Pharmacological Agents for Type 2 Diabetes: Sulfonylureas, Meglitinides, Metformin, Thiazolidinediones, α-Glucosidase Inhibitors, and Emerging Approaches 16 January 2010 3:50 UTC www.endotext.org [Source type: Academic]

^ However, the trial was limited by a high drop-out rate, and longer-term effects of the drug will require further study.
  • Chapter 14. Oral Pharmacological Agents for Type 2 Diabetes: Sulfonylureas, Meglitinides, Metformin, Thiazolidinediones, α-Glucosidase Inhibitors, and Emerging Approaches 16 January 2010 3:50 UTC www.endotext.org [Source type: Academic]

^ Weight reduction was significant in 5 of the 6 adolescent trials; similarly, these studies were limited by weak study design and small patient population.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]

[55] .Observational studies conducted by the University of Dundee have shown a decrease of 25–37% in cancer cases in diabetics taking metformin.^ Sulphonylureas and cancer: a case-control study.
  • Metformin in the treatment of diabetes mellitus 16 January 2010 3:50 UTC www.uptodate.com [Source type: Academic]

^ Studies show that more than half of patients currently taking medication to manage their type 2 diabetes are still not reaching blood glucose goals[1].
  • Eucreas®, a single-tablet combination of Galvus® and metformin, set for launch in first EU countries as new treatment for type 2 diabetes 16 January 2010 3:50 UTC www.novartis.com [Source type: Academic]

^ Comment Metformin is a biguanide anti-diabetic that works by decreasing the amount of sugar that the liver produces and the intestines absorb.

[56][57]
.A single randomized controlled trial suggested that metformin may reduce weight gain in patients taking atypical antipsychotics, particularly when combined with lifestyle interventions (education, dieting, and exercise).^ Treatment is combined with a balanced diet and exercise.
  • Metformin 16 January 2010 3:50 UTC metformin.biz [Source type: FILTERED WITH BAYES]

^ Some people taking metformin may lose weight.
  • Health: Biguanides for type 2 diabetes; Biguanides do not cause low blood sugar ... 16 January 2010 3:50 UTC www.maimonidesmed.org [Source type: FILTERED WITH BAYES]

^ For those of you that are taking Metformin for weight loss, what is you diet like?
  • Metformin and weight loss - Weight Loss Alternatives - MedHelp 16 January 2010 3:50 UTC www.medhelp.org [Source type: General]

[58]

Formulations

Metformin 500 mg tablets
.Metformin is sold under several trade names, including Glucophage XR, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex, and Diaformin.^ Fortamet™ Glucophage® Glucophage® XR Glumetza® Metformin Riomet™ Metformin Hydrochloride Modified-release tablet .
  • Metformin 16 January 2010 3:50 UTC www.stjohn.org [Source type: General]

^ Metformin ( INN ; trade names Glucophage , Diabex , Diaformin , Fortamet , Riomet , Glumetza and others) is an anti-diabetic drug from the biguanide class of oral antihyperglycemic agents.

^ Metformin is also sold under the brand names Glucophage and Glucophage XR, and is found in pills...
  • Metformin - Kosmix : Reference, Videos, Images, News, Shopping and more... 16 January 2010 3:50 UTC www.kosmix.com [Source type: General]

Metformin IR (immediate release) is available in 500 mg, 850 mg, and 1000 mg tablets, all now generic in the US.
.Metformin SR (slow release) or XR (extended release) was introduced in 2004, in 500 mg and 750 mg strengths, mainly to counteract the most common gastrointestinal side effects, as well as to increase patient compliance by reducing pill burden.^ The most common side effects of metformin are: .
  • Health: Biguanides for type 2 diabetes; Biguanides do not cause low blood sugar ... 16 January 2010 3:50 UTC www.maimonidesmed.org [Source type: FILTERED WITH BAYES]
  • Evansville,IN Metformin (Glucophage) for polycystic ovary syndrome; ... 16 January 2010 3:50 UTC www.stmarys.org [Source type: Academic]
  • Exempla Healthcare Online Library 16 January 2010 3:50 UTC www.exempla.org [Source type: Academic]
  • Citizens Health Information 16 January 2010 3:50 UTC www.citizensmemorial.com [Source type: Academic]
  • CIGNA - Biguanides for type 2 diabetes 16 January 2010 3:50 UTC www.cigna.com [Source type: FILTERED WITH BAYES]

^ Does Metformin Oral have any side effects?
  • Metformin Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD 16 January 2010 3:50 UTC www.webmd.com [Source type: General]

^ Glyburide 2.5 mg and metformin hydrochloride 500 mg .
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

.No difference in effectiveness exists between the two preparations.^ No difference in effectiveness exists between the two preparations.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ There was no difference between metformin- and nonmetformin-treated patients in mortality, cardiac, renal, or neurologic morbidity ( Table 5 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ A single-blind crossover study showed no difference in insulin resistance between the placebo and metformin arms of the trial after treatment.
  • eMJA: Norman et al, Metformin and intervention in polycystic ovary syndrome 16 January 2010 3:50 UTC www.mja.com.au [Source type: Academic]

Combinations with other drugs

.Metformin is sometimes prescribed to type 2 diabetes patients in combination with rosiglitazone.^ Metformin is often prescribed to type 2 diabetes patients in combination with rosiglitazone .
  • Metformin 16 January 2010 3:50 UTC www.diabetesdaily.com [Source type: Academic]
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Metformin should not be prescribed for patients with: .
  • Chapter 14. Oral Pharmacological Agents for Type 2 Diabetes: Sulfonylureas, Meglitinides, Metformin, Thiazolidinediones, α-Glucosidase Inhibitors, and Emerging Approaches 16 January 2010 3:50 UTC www.endotext.org [Source type: Academic]

^ Metformin monotherapy for type 2 diabetes mellitus.
  • Metformin (generic), Glucophage News - Topix 16 January 2010 3:50 UTC www.topix.com [Source type: General]

.This drug actively reduces insulin resistance, complementing the action of the metformin.^ This drug actively reduces insulin resistance, complementing the action of the metformin.
  • Metformin 16 January 2010 3:50 UTC www.diabetesdaily.com [Source type: Academic]
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Can metformin reduce insulin resistance in polycystic ovary syndrome?
  • Metformin for PCOS & Pregnancy - Fertility Plus 16 January 2010 3:50 UTC www.fertilityplus.org [Source type: Academic]

^ Re: insulin resistance, benefits of metformin .
  • ≡ METFORMIN ≡ meridia - Canada Pharmacy - Wholesale ... ≡ insulin resistance 16 January 2010 3:50 UTC fabar.2trom.com [Source type: FILTERED WITH BAYES]

.In 2002, the two drugs were combined into a single product, Avandamet, marketed by GlaxoSmithKline.^ Brand names of combination products Actoplus Met® (containing Metformin and Pioglitazone) Avandamet® (containing Metformin and Rosiglitazone) Glucovance® (containing Metformin and Glyburide) Janumet® (containing Metformin and Sitagliptin) Metaglip® (containing Metformin and Glipizide) .
  • Metformin :: Buy Metformin (Buy Generic Glucophage) 16 January 2010 3:50 UTC buymetformin.net [Source type: General]

^ Also, metformin is available as part of combination products with two different sulfonylureas (glyburide and glipizide), called Glucovance and Metaglip, respectively.
  • Diabetes Monitor - Diabetes Monitor - Metformin Questions And Answers 16 January 2010 3:50 UTC www.diabetesmonitor.com [Source type: General]

^ Third, these companies receive the large benefit of the marketing and advertising that goes into pushing the innovator drug.
  • Metformin 16 January 2010 3:50 UTC metformin.biz [Source type: FILTERED WITH BAYES]

[59] .In 2005, all current stock of Avandamet was seized by the FDA and removed from the market, after inspections showed the factory where it was produced was violating Good Manufacturing Practices.^ In 2005, all current stock of Avandamet was seized by the FDA and removed from the market, after inspections showed the factory where it was produced was violating Good Manufacturing Practices .
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

[60] .The drug pair continued to be prescribed separately in the absence of Avandamet, which was available again by the end of that year.^ The drug pair continued to be prescribed separately in the absence of Avandamet, which was available again by the end of that year.
  • Metformin 16 January 2010 3:50 UTC www.diabetesdaily.com [Source type: Academic]
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ While this drug may be prescribed for children as young as 10 years of age for selected conditions, precautions do apply.

^ The institutional policy for perioperative administration of oral hypoglycemic medications was to continue the usual prescribed dose of oral hypoglycemic drug until the night before surgery, but not on the day of surgery.
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

.In the United States, metformin is also available in combination with pioglitazone (trade name Actoplus Met), the sulfonylureas glipizide (trade name Metaglip) and glibenclamide (known as glyburide in the United States, trade name Glucovance), the dipeptidyl peptidase-4 inhibitor sitagliptin (trade name Janumet), and the meglitinide repaglinide (PrandiMet).^ My Dr. I start Metformin Metformin Metformin hydrochloride Metformin hydrochloride er Metformin-glipizide Metformin-glyburide Metformin-pioglitazone Metformin-repaglinide Metformin-rosiglitazone Metformin-sitagliptin .
  • Metformin and weight loss - Weight Loss Alternatives - MedHelp 16 January 2010 3:50 UTC www.medhelp.org [Source type: General]

^ Brand names of combination products Actoplus Met® (containing Metformin and Pioglitazone) Avandamet® (containing Metformin and Rosiglitazone) Glucovance® (containing Metformin and Glyburide) Janumet® (containing Metformin and Sitagliptin) Metaglip® (containing Metformin and Glipizide) .
  • Metformin :: Buy Metformin (Buy Generic Glucophage) 16 January 2010 3:50 UTC buymetformin.net [Source type: General]

^ Also, metformin is available as part of combination products with two different sulfonylureas (glyburide and glipizide), called Glucovance and Metaglip, respectively.
  • Diabetes Monitor - Diabetes Monitor - Metformin Questions And Answers 16 January 2010 3:50 UTC www.diabetesmonitor.com [Source type: General]

.Generic formulations of metformin/glipizide and metformin/glibenclamide are available.^ Generic formulations are now available.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Generic metformin tablets are available.
  • Metformin 16 January 2010 3:50 UTC metformin.biz [Source type: FILTERED WITH BAYES]

^ In the United States, metformin is also available in combination with pioglitazone (trade name Actoplus Met ), the sulfonylureas glipizide (trade name Metaglip ) and glibenclamide (trade name Glucovance ), and the dipeptidyl peptidase-4 inhibitor sitagliptin (trade name Janumet ).
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

A generic formulation of metformin/rosiglitazone from Teva has received tentative approval from the FDA, and is expected to reach the market in early 2012.[61]

Contraindications

.Metformin is contraindicated in people with any condition that could increase the risk of lactic acidosis, including kidney disorders (creatinine levels over 150 μmol/l,[62] although this is an arbitrary limit), lung disease and liver disease.^ Many metformin-treated patients have contraindications to therapy with metformin, which theoretically increases risk for lactic acidosis.
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ The most significant risk associated with metformin is that of lactic acidosis.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ Contrast agents: May increase the risk of metformin-induced lactic acidosis.
  • Metformin 16 January 2010 3:50 UTC www.umm.edu [Source type: Academic]
  • Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

.According to the prescribing information, heart failure, in particular, unstable or acute congestive heart failure increases risk of lactic acidosis with metformin.^ The most significant risk associated with metformin is that of lactic acidosis.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ Contrast agents: May increase the risk of metformin-induced lactic acidosis.
  • Metformin 16 January 2010 3:50 UTC www.umm.edu [Source type: Academic]
  • Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis.
  • Metformin Hydrochloride (Tablet, Film Coated) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

[63] .A 2007 systematic review of controlled trials, however, suggested that metformin is the only anti-diabetic drug not associated with any measurable harm in people with heart failure, and that it may reduce mortality in comparison with other anti-diabetic agents.^ Metformin is a useful agent but significant mortality is associated with drug-induced lactic acidosis.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Metformin is an anti-diabetic .
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Mary Metformin is an anti-diabetic drug.
  • METFORMIN - Forum’s Choice Program at ALS TDI - ALS Forum 16 January 2010 3:50 UTC www.als.net [Source type: Academic]

[64]
.It is recommended that metformin be temporarily discontinued before any radiographic study involving iodinated contrast (such as a contrast-enhanced CT scan or angiogram), as contrast dye may temporarily impair kidney function, indirectly leading to lactic acidosis by causing retention of metformin in the body.^ Contrast agents: May increase the risk of metformin-induced lactic acidosis.
  • Metformin 16 January 2010 3:50 UTC www.umm.edu [Source type: Academic]
  • Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ An overdose of metformin is likely to cause lactic acidosis..
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ It is recommended that metformin be temporarily discontinued before any radiographic study involving iodinated contrast (such as a contrast-enhanced CT scan or angiogram ), as contrast dye may temporarily impair kidney function, indirectly leading to lactic acidosis by causing retention of metformin in the body.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

[65][66] .It is recommended that metformin be resumed after two days, assuming kidney function is normal.^ It is recommended that metformin be resumed after two days, assuming kidney function is normal.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ It is recommended that metformin be temporarily discontinued before any radiographic procedure involving iodinated contrast (such as a CT scan or angiogram ) as contrast may temporarily impair kidney function and indirectly lead to lactic acidosis.

^ Oral glucose tolerance tests at baseline were comparable in the two groups, while after two doses of metformin, individuals with reduced-function alleles showed slightly higher glucose levels.
  • Journal of Clinical Investigation -- Pharmacogenetics of metformin response: a step in the path toward personalized medicine 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

[65][66]

Adverse effects

.The most common adverse effect of metformin is gastrointestinal upset, including diarrhea, cramps, nausea, vomiting and increased flatulence; metformin is more commonly associated with gastrointestinal side effects than most other anti-diabetic drugs.^ The most common side effects of metformin are: .
  • Exempla Healthcare Online Library 16 January 2010 3:50 UTC www.exempla.org [Source type: Academic]

^ Diabetes, Type 2 : I have been taking Metformin for about a month and have not had any side effects.
  • metformin systemic User Reviews at Drugs.com 16 January 2010 3:50 UTC www.drugs.com [Source type: General]

^ Does Metformin Oral have any side effects?
  • Metformin Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD 16 January 2010 3:50 UTC www.webmd.com [Source type: General]

[25] .The most serious potential side effect of metformin use is lactic acidosis; this complication is very rare, and the vast majority of these cases seem to be related to comorbid conditions such as impaired liver or kidney function, rather than to the metformin itself.^ Do not use metformin for a condition for which it was not prescribed.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

^ The most significant risk associated with metformin is that of lactic acidosis.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ The most serious side effect of metformin is lactic acidosis ; this complication is rare if the contra-indications are followed, as it seems limited to those with impaired liver or kidney function.

[67]
.Metformin has also been reported to reduce the blood levels of thyroid-stimulating hormone in patients with hypothyroidism,[68] and, in men, lutenizing hormone and testosterone.^ Metformin also reduced hemoglobin A1C levels, a blood measurement of glycosylation.
  • LE Magazine, September 2001 - Report: The Multiple Benefits of Metformin 16 January 2010 3:50 UTC www.lef.org [Source type: Academic]

^ Metformin lowers blood sugar levels by: .
  • Exempla Healthcare Online Library 16 January 2010 3:50 UTC www.exempla.org [Source type: Academic]

^ Metformin lowers blood glucose levels by sensitizing target tissues to insulin, inhibits hepatic glucose production, and increases peripheral glucose uptake ( 1 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

[69][70] .The clinical significance of these changes is still unknown.^ The clinical relevance of these decreases is unknown.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

^ There was no clinically significant change with metformin in any of the parameters we studied .
  • Metformin & glitazones: Do they really help PCOS patients? — The Journal of Family Practice 16 January 2010 3:50 UTC www.jfponline.com [Source type: Academic]

^ Diabetic patients often have chronic vascular changes that lead to clinically significant vascular disease.
  • Skyscape Content: Lactic acidosis: Lactic acidosis associated with metformin use in treatment of type 2 diabetes mellitus 16 January 2010 3:50 UTC mediwire.skyscape.com [Source type: Academic]

Gastrointestinal

.In a clinical trial of 286 subjects, 53.2% of the 141 who were given immediate-release metformin (as opposed to placebo) reported diarrhea, versus 11.7% for placebo, and 25.5% reported nausea/vomiting, versus 8.3% for those on placebo.^ Blood pressure Two trials comparing metformin with placebo reported blood pressure.
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ In a clinical trial of 286 subjects, 53.2% of the 141 who were given Metformin IR (as opposed to placebo ) reported diarrhea, versus 11.7% for placebo, and 25.5% reported nausea/vomiting, versus 8.3% for those on placebo.

^ In a clinical trial of 286 subjects, 53.2% of the 141 who were given immediate-release metformin (as opposed to placebo ) reported diarrhea, versus 11.7% for placebo, and 25.5% reported nausea/vomiting, versus 8.3% for those on placebo.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

[71]
.Gastrointestinal upset can cause severe discomfort for patients; it is most common when metformin is first administered, or when the dose is increased.^ The most common, cause of infertility.
  • NSAA : National Ski Areas Association : The GREENROOM 16 January 2010 3:50 UTC www.nsaa.org [Source type: Academic]

^ The most common side effects of metformin are: .
  • Exempla Healthcare Online Library 16 January 2010 3:50 UTC www.exempla.org [Source type: Academic]

^ Gastrointestinal upset can cause severe discomfort for patients; it is most common when metformin is first administered, or when the dose is increased.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

.The discomfort can often be avoided by beginning at a low dose (1 to 1.7 grams per day) and increasing the dose gradually.^ The discomfort can often be avoided by beginning at a low dose (1 to 1.7 grams per day) and increasing the dose gradually.

^ Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

^ However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

.Gastrointestinal upset after prolonged, steady use is less common.^ Gastrointestinal upset after prolonged, steady use is less common.
  • Metformin 16 January 2010 3:50 UTC www.diabetesdaily.com [Source type: Academic]
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ The most common side effect of metformin is gastrointestinal upset, including diarrhea , cramps, nausea and vomiting.

^ Gastrointestinal upset can cause severe discomfort for patients; it is most common when metformin is first administered, or when the dose is increased.
  • Metformin 16 January 2010 3:50 UTC www.diabetesdaily.com [Source type: Academic]
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

.Long-term use of metformin has been associated with increased homocysteine levels[72] and malabsorption of vitamin B12.^ SHBG is increased during metformin use.
  • metformin's effect on testosterone - Mind and Muscle Forums 16 January 2010 3:50 UTC www.mindandmuscle.net [Source type: FILTERED WITH BAYES]

^ "Metformin-associated vitamin B12 deficiency".
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Long-term therapy with metformin is associated with decreased intestinal absorption of vitamin B 12 and folate.
  • Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study -- Wu et al. 165 (3): 352 -- Am J Psychiatry 16 January 2010 3:50 UTC ajp.psychiatryonline.org [Source type: Academic]

[73][74] .Higher doses and prolonged use are associated with increased incidence of B12 deficiency, and some researchers recommend screening or prevention strategies.^ Higher doses and prolonged use are associated with increased incidence of B 12 deficiency, and some researchers recommend screening or prevention strategies.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ The disadvantages are the gastro-intestinal side effects and the potential risk of vitamin B 12 and folic acid deficiency during long-term use.
  • Glucophage/Metformin Info - Professional Muscle 16 January 2010 3:50 UTC www.professionalmuscle.com [Source type: FILTERED WITH BAYES]

^ Glyburide: The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised.
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

[75]

Lactic acidosis

.The most serious potential adverse effect of biguanide use is lactic acidosis.^ Lactic acidosis while using Glucophage.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ This may be a sign of lactic acidosis or another serious side effect.
  • Diabetes Monitor - Diabetes Monitor - Metformin Questions And Answers 16 January 2010 3:50 UTC www.diabetesmonitor.com [Source type: General]

^ A serious-though rare-side effect of metformin is lactic acidosis..
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

.Phenformin, another biguanide, was withdrawn from the market because of an increased risk of lactic acidosis (up to 60 cases per million patient-years).^ Lactic acidosis; 3 cases per 100,000 patient-years of treatment (rare) .
  • Chapter 14. Oral Pharmacological Agents for Type 2 Diabetes: Sulfonylureas, Meglitinides, Metformin, Thiazolidinediones, α-Glucosidase Inhibitors, and Emerging Approaches 16 January 2010 3:50 UTC www.endotext.org [Source type: Academic]

^ The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]
  • Metformin Hydrochloride (Tablet, Film Coated) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

^ The risk of lactic acidosis is increased in any patient with CHF requiring pharmacologic management.
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

.However, metformin is safer than phenformin, and the risk of developing lactic acidosis is not increased by the medication so long as it is not prescribed to known high-risk groups.^ The most significant risk associated with metformin is that of lactic acidosis.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ Contrast agents: May increase the risk of metformin-induced lactic acidosis.
  • Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ Lactic acidosis is a medical emergency .
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

[76]
.Lactate uptake by the liver is diminished with metformin administration because lactate is a substrate for hepatic gluconeogenesis, a process which metformin inhibits.^ Metformin lowers blood glucose levels by sensitizing target tissues to insulin, inhibits hepatic glucose production, and increases peripheral glucose uptake ( 1 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ Metformin decreases hepatic glucose production, decreasing intestinal absorption of glucose, and improves insulin sensitivity (increases peripheral glucose uptake and utilization).

^ Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

.In healthy individuals, this slight excess is simply cleared by other mechanisms (including uptake by the kidneys, when their function is unimpaired), and no significant elevation in blood levels of lactate occurs.^ Metformin lowers blood glucose levels by sensitizing target tissues to insulin, inhibits hepatic glucose production, and increases peripheral glucose uptake ( 1 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ The elevated insulin levels may have gonadotropin-augmenting effects on ovarian function.
  • Metformin & glitazones: Do they really help PCOS patients? — The Journal of Family Practice 16 January 2010 3:50 UTC www.jfponline.com [Source type: Academic]

^ Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems.
  • Metformin Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD 16 January 2010 3:50 UTC www.webmd.com [Source type: General]
  • Glipizide-Metformin Oral Drug information on Uses, Side Effects, Interactions, and User Reviews on RxList 16 January 2010 3:50 UTC fdb.rxlist.com [Source type: General]

[24] .When there is impaired renal function, however, clearance of metformin (and lactate) is reduced and the drug may accumulate, leading to lactic acidosis.^ Metformin lactic acidosis.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Acidosis lactic metformin infertility .
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Acidosis lactic metformin.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

.Because metformin decreases liver uptake of lactate, any condition which may precipitate lactic acidosis is a contraindication to its use.^ Lactic acidosis while using Glucophage.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Metformin lactic acidosis.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Acidosis lactic metformin infertility .
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

.Common causes of increased lactic acid production include alcoholism (due to depletion of NAD+ stores), heart failure, and respiratory disease (due to inadequate oxygenation of tissues); the most common cause of impaired lactic acid excretion is kidney disease.^ The most common contraindication was a history of congestive heart failure.
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ This is caused by a build-up of lactic acid.
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

^ Lactic acidosis is caused by the buildup of lactic acids .
  • Diabetes, Obesity & Metabolism - Abstract: Volume 3(3) June 16 January 2010 3:50 UTC carlowweather.com [Source type: FILTERED WITH BAYES]

[77]
.It has also been suggested that metformin increases production of lactate in the small intestine; this could potentially contribute to lactic acidosis in patients with risk factors.^ Many metformin-treated patients have contraindications to therapy with metformin, which theoretically increases risk for lactic acidosis.
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ The most significant risk associated with metformin is that of lactic acidosis.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ Metformin-associated lactic acidosis in a patient with liver disease.
  • NEJM -- Metformin 16 January 2010 3:50 UTC content.nejm.org [Source type: Academic]

[78] .However, the clinical significance of this is unknown, and the risk of metformin-associated lactic acidosis is most commonly attributed to decreased hepatic uptake rather than increased intestinal production.^ The most significant risk associated with metformin is that of lactic acidosis.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ Incidence of lactic acidosis in Metformin users.
  • Metformin 16 January 2010 3:50 UTC www.phlaunt.com [Source type: Academic]

^ Risk of fatal and nonfatal lactic acidosis with...
  • Metformin (generic), Glucophage Forum - Topix 16 January 2010 3:50 UTC www.topix.com [Source type: General]
  • on metformin for 8 weeks and no periods - Topix 16 January 2010 3:50 UTC www.topix.net [Source type: General]

[24][77][79]

Overdosage

.A review of intentional and accidental metformin overdoses reported to poison control centers over a five-year period found that serious adverse events were rare, though elderly patients appeared to be at greater risk.^ No trial reported any serious adverse events.
  • Metformin in polycystic ovary syndrome: systematic review and meta-analysis -- Lord et al. 327 (7421): 951 -- BMJ 16 January 2010 3:50 UTC www.bmj.com [Source type: Academic]

^ Adult metformin ingestions reported to Texas poison control centers, 2000-2006.
  • NEJM -- Metformin 16 January 2010 3:50 UTC content.nejm.org [Source type: Academic]

^ Our major observations were that diabetics who ever used metformin, especially those with greater than five years of use, had a reduced risk of pancreatic cancer compared to diabetics who had not taken these drugs," said Donghui Li, PhD, of The University of Texas M. D. Anderson Cancer Center and lead author of the study.
  • Metformin associated with reduced risk of pancreatic cancer in diabetics 16 January 2010 3:50 UTC www.news-medical.net [Source type: Academic]

[80] .A similar study where cases were reported to Texas poison control centers between the years 2000 and 2006 found that ingested doses of more than 5,000 mg were more likely to involve serious medical outcomes in adults.^ (Doses above 2,000 milligrams have not been shown to be any more effective than a 2,000-milligram dose.

^ Adult metformin ingestions reported to Texas poison control centers, 2000-2006.
  • NEJM -- Metformin 16 January 2010 3:50 UTC content.nejm.org [Source type: Academic]

^ In women with gestational diabetes, glyburide is more effective than metformin for achieving glycemic control, according to a study in the January issue of Obstetrics & Gynecology .
  • Metformin (generic), Glucophage News - Topix 16 January 2010 3:50 UTC www.topix.com [Source type: General]

[81] .Survival following intentional overdoses with up to 63,000 mg (63 g) of metformin have been reported in the medical literature.^ Nondiabetics using metformin may start off at 500 mg a day and gradually build up to 1000-1500 mg a day.
  • Glucophage (metformin) 16 January 2010 3:50 UTC qualitycounts.com [Source type: Academic]

^ Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions.
  • Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes -- Lund et al. 158 (5): 631 -- European Journal of Endocrinology 16 January 2010 3:50 UTC www.eje-online.org [Source type: Academic]

^ Do not take ARROW - METFORMIN if you have any of the following medical conditions: .
  • Consumer Medicine Information 16 January 2010 3:50 UTC www.medsafe.govt.nz [Source type: General]

[82] .Fatalities following overdose are rare, but do occur.^ Although rare, if lactic acidosis does occur, it can be fatal in up to half the people who develop it.
  • Diabetes Monitor - Diabetes Monitor - Metformin Questions And Answers 16 January 2010 3:50 UTC www.diabetesmonitor.com [Source type: General]

^ Although rare, if lactic acidosis does occur, it can be fatal in up to half the cases.
  • Diabetes Monitor - Diabetes Monitor - Metformin Questions And Answers 16 January 2010 3:50 UTC www.diabetesmonitor.com [Source type: General]

^ WARNINGS: Lactic Acidosis:: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

[83][84][85] .In healthy children, unintentional doses of less than 1,700 mg are unlikely to cause any significant toxic effects.^ Metformin is, however, a low-potency compound that is used at high doses, resulting in only modest net efficacy; in addition, significant side effects can occur ( 2 ).
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

^ Bioavailability: 18% with 2.5 mg glyburide/500 mg metformin dose; 7% with 5 mg glyburide/500 mg metformin dose; bioavailability is greater than that of Micronase brand of glyburide and therefore not bioequivalent .
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ Recommended Dosing Schedule: Adults: In general, clinically significant responses are not seen at doses below 1500 mg per day.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

[86]
.The most common symptoms following overdose appear to include vomiting, diarrhea, abdominal pain, tachycardia, drowsiness, and hyperglycemia.^ Symptoms of overdose may include: extreme tiredness weakness discomfort vomiting upset stomach stomach pain decreased appetite deep, rapid breathing shortness of breath dizziness light-headedness abnormally fast or slow heartbeat flushing of the skin muscle pain feeling cold .
  • Metformin - Kosmix : Reference, Videos, Images, News, Shopping and more... 16 January 2010 3:50 UTC www.kosmix.com [Source type: General]

^ The most common side effects associated with metformin are gastrointestinal in nature: abdominal pain, constipation, distended abdomen, diarrhea, dyspepsia/heartburn, taste disturbance, and flatulence.
  • Polycystic Ovary Syndrome and Pregnancy: Is Metformin the Magic Bullet? — Diabetes Spectrum 16 January 2010 3:50 UTC spectrum.diabetesjournals.org [Source type: Academic]

^ The major side effects of metformin are gastrointestinal and include an increase in the frequency of bowel movements, diarrhea, nausea, and abdominal pain.

[81][84] .The major potentially life-threatening complication of metformin overdose is lactic acidosis, which is due to lactate accumulation.^ The major potentially life-threatening complication of metformin overdose is lactic acidosis .
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ There is a life threatening side effect of metformin called lactic acidosis .
  • Drug and pharmacy related information 16 January 2010 3:50 UTC nichollsvi.tripod.com [Source type: Academic]

^ Metformin and lactic acidosis: cause or coincidence?
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

[87][88] .Treatment of metformin overdose is generally supportive as there is no specific antidote.^ Treatment of metformin overdose is generally supportive, but may include sodium bicarbonate to address acidosis and standard hemodialysis or continuous veno-venous hemofiltration to rapidly remove metformin and correct acidosis.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ The metformin treatment was generally well tolerated and a detailed description of the data regarding the safety has already been shown (Palomba et al ., 2005a ).
  • Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome -- Palomba et al. 21 (2): 457 -- Human Reproduction 16 January 2010 3:50 UTC humrep.oxfordjournals.org [Source type: Academic]

^ However, there are presently only limited data to support this premise, particularly with newer generation agents.
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

.Lactic acidosis is initially treated with sodium bicarbonate, although high doses are not recommended as this may increase intracellular acidosis.^ Metformin is similar in chemical structure to phenformin, which was removed from the United States market because of an unacceptably high incidence of life-threatening lactic acidosis.
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ Treatment of metformin overdose is generally supportive, but may include sodium bicarbonate to address acidosis and standard hemodialysis or continuous veno-venous hemofiltration to rapidly remove metformin and correct acidosis.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Higher doses and prolonged use are associated with increased incidence of B 12 deficiency, and some researchers recommend screening or prevention strategies.
  • Metformin 16 January 2010 3:50 UTC www.diabetesdaily.com [Source type: Academic]
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

[85] .Acidosis that does not respond to administration of sodium bicarbonate may require further management with standard hemodialysis or continuous veno-venous hemofiltration.^ Treatment of metformin overdose is generally supportive, but may include sodium bicarbonate to address acidosis and standard hemodialysis or continuous veno-venous hemofiltration to rapidly remove metformin and correct acidosis.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Second-line therapy for management of type 2 diabetes (NIDDM) when hyperglycemia cannot be managed with a sulfonylurea or metformin; combination therapy with a thiazolidinedione may be required to achieve additional control.
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ The risk of lactic acidosis is increased in any patient with CHF requiring pharmacologic management.
  • Glyburide and Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

.Additionally, due to metformin’s low molecular weight and lack of plasma protein binding, these techniques also have the benefit of efficiently removing metformin from blood plasma, preventing further lactate over-production.^ Further, the addition of metformin to orlistat does not appear to provide any additional benefit.
  • Role of Metformin for Weight Management in Patients Without Type 2 Diabetes -- Desilets et al. 42 (6): 817 -- The Annals of Pharmacotherapy 16 January 2010 3:50 UTC www.theannals.com [Source type: Academic]

^ Metformin is best used in addition to eating a healthy diet, losing weight, and exercising regularly.
  • Exempla Healthcare Online Library 16 January 2010 3:50 UTC www.exempla.org [Source type: Academic]
  • Citizens Health Information 16 January 2010 3:50 UTC www.citizensmemorial.com [Source type: Academic]

^ Metformin lowers blood glucose levels by sensitizing target tissues to insulin, inhibits hepatic glucose production, and increases peripheral glucose uptake ( 1 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

[89][90][91]

Chemistry

.The usual synthesis of metformin, originally described in 1922 and reproduced in multiple later patents and publications, involves the reaction of dimethylamine hydrochloride and 2-cyanoguanidine (dicyandiamide) with heating.^ Pediatric Patients: In clinical trials with metformin hydrochloride tablets, USP in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

^ Release of Metformin Hydrochloride from Chewing Gum [0089] The paste preparation of Example 2 was made into three different chewing gum compositions using the known method described above.
  • Compositions for Oral Transmucosal Delivery of Metformin - Patent application 16 January 2010 3:50 UTC www.faqs.org [Source type: Reference]

^ Pediatrics: The usual starting dose of metformin hydrochloride tablets, USP is 500 mg twice a day, given with meals.
  • Metformin Hydrochloride (Tablet, Extended Release) | D2R Server publishing the Dailymed Dataset 16 January 2010 3:50 UTC www4.wiwiss.fu-berlin.de [Source type: Academic]

[8][92]
Metformin synthesis.svg
.According to the procedure described in 1975 Aron patent[93] and the Pharmaceutical Manufacturing Encyclopedia,[94] equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and equimolar amount of hydrogen chloride is slowly added.^ It can also be used to make chewable capsules as described, for example, in U.S. Patent Application Publication No.
  • Compositions for Oral Transmucosal Delivery of Metformin - Patent application 16 January 2010 3:50 UTC www.faqs.org [Source type: Reference]

.The mixture begins to boil on its own, and after cooling, metformin hydrochloride precipitates with 96% yield.^ GLUCOPHAGE (metformin hydrochloride tablets) lowers the amount of sugar in your blood by helping your body respond better to its own insulin.
  • Diabetes Monitor - Diabetes Monitor - Metformin Questions And Answers 16 January 2010 3:50 UTC www.diabetesmonitor.com [Source type: General]

Pharmacokinetics

.Metformin has an oral bioavailability of 50–60% under fasting conditions, and is absorbed slowly.^ What conditions does Metformin Oral treat?
  • Metformin Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD 16 January 2010 3:50 UTC www.webmd.com [Source type: General]

^ They may also be determined by measuring the bioavailability of known oral formulations of metformin hydrochloride.
  • Compositions for Oral Transmucosal Delivery of Metformin - Patent application 16 January 2010 3:50 UTC www.faqs.org [Source type: Reference]

^ Under conditions where SREBP-1 was induced by insulin, incubation of rat hepatocytes with metformin or AICAR strongly suppressed SREBP-1 mRNA expression (Figure 5 a).
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

[95][96] .Peak plasma concentrations (Cmax) are reached within one to three hours of taking immediate-release metformin and four to eight hours with extended-release formulations.^ Glumetza is metformin in an extended release format.
  • Metformin side effects - Diabetes Forums 16 January 2010 3:50 UTC www.diabetesforums.com [Source type: General]

^ As used herein, "approximately equal" means that the peak plasma concentration of metformin after administration of the pharmaceutical composition of the invention (assessed using standard bioavailability measurements) is within 10% of the peak metformin plasma concentration after administration of an oral tablet formulation of metformin.
  • Compositions for Oral Transmucosal Delivery of Metformin - Patent application 16 January 2010 3:50 UTC www.faqs.org [Source type: Reference]

^ FIG. 1 is a graph showing metformin plasma concentrations (ng/ml) over time.
  • Compositions for Oral Transmucosal Delivery of Metformin - Patent application 16 January 2010 3:50 UTC www.faqs.org [Source type: Reference]

[95][96] .The plasma protein binding of metformin is negligible, as reflected by its very high apparent volume of distribution (300–1000 L after a single dose).^ Protein binding: Negligible .
  • Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ Hemodialysis has been shown to lower plasma metformin levels, however, a rebound in levels?presumably due to a potentially long half-life (24 hours) and large distribution volume?has been described.
  • Skyscape Content: Lactic acidosis: Lactic acidosis associated with metformin use in treatment of type 2 diabetes mellitus 16 January 2010 3:50 UTC mediwire.skyscape.com [Source type: Academic]

^ Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein Ling He et al,, Cell Volume 137, Issue 4, 635-646, 15 May 2009.
  • Metformin 16 January 2010 3:50 UTC www.phlaunt.com [Source type: Academic]

.Steady state is usually reached in one or two days.^ The regular tablet is usually taken with meals two or three times a day.
  • Metformin - Kosmix : Reference, Videos, Images, News, Shopping and more... 16 January 2010 3:50 UTC www.kosmix.com [Source type: General]

^ After one day the cells were plated into 100 mm dishes and then selection with hygromycin (200 μ g/ml) was initiated two days later.
  • Journal of Molecular Signaling | Full text | Cell cycle arrest in metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1 16 January 2010 3:50 UTC www.jmolecularsignaling.com [Source type: Academic]

^ It is usually started at a dose of 500 milligrams and slowly raised every one to two weeks to the maximum dose that can be tolerated without side effects.

[95]
Metformin is not metabolized. .It is cleared from the body by tubular secretion and excreted unchanged in the urine; metformin is undetectable in blood plasma within 24 hours of a single oral dose.^ Metformin is excreted unchanged by the kidney.
  • Skyscape Content: Lactic acidosis: Lactic acidosis associated with metformin use in treatment of type 2 diabetes mellitus 16 January 2010 3:50 UTC mediwire.skyscape.com [Source type: Academic]

^ Hemodialysis has been shown to lower plasma metformin levels, however, a rebound in levels?presumably due to a potentially long half-life (24 hours) and large distribution volume?has been described.
  • Skyscape Content: Lactic acidosis: Lactic acidosis associated with metformin use in treatment of type 2 diabetes mellitus 16 January 2010 3:50 UTC mediwire.skyscape.com [Source type: Academic]

^ As used herein, "approximately equal" means that the peak plasma concentration of metformin after administration of the pharmaceutical composition of the invention (assessed using standard bioavailability measurements) is within 10% of the peak metformin plasma concentration after administration of an oral tablet formulation of metformin.
  • Compositions for Oral Transmucosal Delivery of Metformin - Patent application 16 January 2010 3:50 UTC www.faqs.org [Source type: Reference]

[95][97] .The average elimination half-life in plasma is 6.2 hours.^ Metformin is not metabolized, rather it is primarily excreted in the urine with an elimination half-life of 6.2 hours.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Hemodialysis has been shown to lower plasma metformin levels, however, a rebound in levels?presumably due to a potentially long half-life (24 hours) and large distribution volume?has been described.
  • Skyscape Content: Lactic acidosis: Lactic acidosis associated with metformin use in treatment of type 2 diabetes mellitus 16 January 2010 3:50 UTC mediwire.skyscape.com [Source type: Academic]

^ In addition, the plasma half-life of 1st generation sulfonylureas is extended (e.g.
  • Chapter 14. Oral Pharmacological Agents for Type 2 Diabetes: Sulfonylureas, Meglitinides, Metformin, Thiazolidinediones, α-Glucosidase Inhibitors, and Emerging Approaches 16 January 2010 3:50 UTC www.endotext.org [Source type: Academic]

[95] .Metformin is distributed to (and appears to accumulate in) red blood cells, with a much longer elimination half-life: 17.6 hours[95] (reported as ranging from 18.5 to 31.5 hours in a single-dose study of non-diabetic people).^ Metformin is not metabolized, rather it is primarily excreted in the urine with an elimination half-life of 6.2 hours.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ OCT1 activity and the ability of metformin to activate AMPK. Next, Oct1 –/– mice dosed with metformin were shown to have plasma exposures and kinetics similar to those of control mice, but with four-fold lower liver accumulation (at 1 hour) and decreased liver AMPK activation.
  • Journal of Clinical Investigation -- Pharmacogenetics of metformin response: a step in the path toward personalized medicine 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

^ Hemodialysis has been shown to lower plasma metformin levels, however, a rebound in levels?presumably due to a potentially long half-life (24 hours) and large distribution volume?has been described.
  • Skyscape Content: Lactic acidosis: Lactic acidosis associated with metformin use in treatment of type 2 diabetes mellitus 16 January 2010 3:50 UTC mediwire.skyscape.com [Source type: Academic]

[97]

Mechanism of action

.Metformin improves hyperglycemia primarily through its suppression of hepatic glucose production (hepatic gluconeogenesis).^ Metformin lowers blood glucose levels by sensitizing target tissues to insulin, inhibits hepatic glucose production, and increases peripheral glucose uptake ( 1 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ A 2001 study showed that metformin stimulates the hepatic enzyme AMP-activated protein kinase (AMPK), which plays an important role in the metabolism of fats and glucose.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ It appears to act mainly by reducing hepatic gluconeogenesis , but it also decreases absorption of glucose from the gastrointestinal tract and increases insulin sensitivity by increasing peripheral utilization of glucose.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

[78] .The "average" person with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one third.^ Lactic acidosis rates in type 2 diabetes.
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ The 'average' person with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one third.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Metformin was started at risk for type 2 diabetics.
  • 888.com: Buy Metformin in Canadian Pharmacy - FREE Worldwide Shipping 16 January 2010 3:50 UTC www.gamblux.com [Source type: General]

[98] .Metformin activates AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats;[99] activation of AMPK is required for metformin's inhibitory effect on the production of glucose by liver cells.^ "Metabolic effects of metformin in non-insulin-dependent diabetes mellitus".
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Adenosine 5' monophosphate-activated protein kinase (AMPK) is involved in metformin action in various cell types.
  • metformin's effect on testosterone - Mind and Muscle Forums 16 January 2010 3:50 UTC www.mindandmuscle.net [Source type: FILTERED WITH BAYES]

^ AMP-activated protein kinase (AMPK) provides a candidate target capable of mediating the beneficial metabolic effects of metformin.
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

[100] .Research published in 2008 further elucidated metformin's mechanism of action, showing that activation of AMPK is required for an increase in the expression of SHP, which in turn inhibits the expression of the hepatic gluconeogenic genes PEPCK and Glc-6-Pase.^ Metformin increases expression of MEF2.
  • METFORMIN - Forum’s Choice Program at ALS TDI - ALS Forum 16 January 2010 3:50 UTC www.als.net [Source type: Academic]

^ Role of AMP-activated protein kinase in mechanism of metformin action .
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

^ Additional studies will be required to further elucidate precise mechanism(s) by which metformin-stimulated AMPK activation could result in inhibition of hepatic glucose production.
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

[101] .Metformin is frequently used in research along with AICAR as an AMPK agonist.^ Figure 3 Discovery and use of a novel small-molecule AMPK inhibitor to establish that the effects of metformin on ACC and glucose production are AMPK dependent.
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

^ Therefore our findings may be of significance for development and use of anti-tumor drugs, such a metformin, that target the AMPK signaling pathway.
  • Journal of Molecular Signaling | Full text | Cell cycle arrest in metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1 16 January 2010 3:50 UTC www.jmolecularsignaling.com [Source type: Academic]

^ Metformin (500 μM) and AICAR (500 μM) activated both AMPKα1 and AMPKα2 complexes demonstrated by immunoprecipitation-AMPK assay.
  • Journal of Clinical Investigation -- Role of AMP-activated protein kinase in mechanism of metformin action 16 January 2010 3:50 UTC www.jci.org [Source type: Academic]

.The mechanism by which biguanides increase the activity of AMPK remains uncertain; however, research suggests that metformin increases the amount of cytosolic AMP (as opposed to a change in total AMP or total AMP/ATP).^ A 2001 study showed that metformin stimulates the hepatic enzyme AMP-activated protein kinase (AMPK), which plays an important role in the metabolism of fats and glucose.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis.
  • Glucophage/Metformin Info - Professional Muscle 16 January 2010 3:50 UTC www.professionalmuscle.com [Source type: FILTERED WITH BAYES]

^ Sirtori CR Pasik C Re-evaluation of a biguanide, metformin: mechanism of action and tolerability.
  • Metformin therapy and clinical uses -- Scarpello and Howlett 5 (3): 157 -- Diabetes and Vascular Disease Research 16 January 2010 3:50 UTC www.dvdres.com [Source type: Academic]

[102]
.In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake, increases fatty acid oxidation,[103] and decreases absorption of glucose from the gastrointestinal tract.^ The mechanism by which PPAR-γ agonists enhance insulin sensitivity of glucose production and utilization is unclear.
  • Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes — Diabetes 16 January 2010 3:50 UTC diabetes.diabetesjournals.org [Source type: Academic]

^ Metformin is a hepatic-selective insulin sensitizer.
  • Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study -- Wu et al. 165 (3): 352 -- Am J Psychiatry 16 January 2010 3:50 UTC ajp.psychiatryonline.org [Source type: Academic]

^ Unlike metformin, rosiglitazone also increases peripheral insulin sensitivity.
  • Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes — Diabetes 16 January 2010 3:50 UTC diabetes.diabetesjournals.org [Source type: Academic]

.Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors.^ Metformin lowers blood glucose levels by sensitizing target tissues to insulin, inhibits hepatic glucose production, and increases peripheral glucose uptake ( 1 ).
  • Recent Metformin Ingestion Does Not Increase In-Hospital Morbidity or Mortality After Cardiac Surgery -- Duncan et al. 104 (1): 42 -- Anesthesia & Analgesia 16 January 2010 3:50 UTC www.anesthesia-analgesia.org [Source type: Academic]

^ Metformin decreases hepatic glucose production, decreasing intestinal absorption of glucose, and improves insulin sensitivity (increases peripheral glucose uptake and utilization).

^ It appears to act mainly by reducing hepatic gluconeogenesis , but it also decreases absorption of glucose from the gastrointestinal tract and increases insulin sensitivity by increasing peripheral utilization of glucose.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

[104] .AMPK probably also plays a role, as metformin administration increases AMPK activity in skeletal muscle.^ A 2001 study showed that metformin stimulates the hepatic enzyme AMP-activated protein kinase (AMPK), which plays an important role in the metabolism of fats and glucose.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis.
  • Glucophage/Metformin Info - Professional Muscle 16 January 2010 3:50 UTC www.professionalmuscle.com [Source type: FILTERED WITH BAYES]

^ Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity.
  • Glucophage/Metformin Info - Professional Muscle 16 January 2010 3:50 UTC www.professionalmuscle.com [Source type: FILTERED WITH BAYES]

[105] .AMPK is known to cause GLUT4 translocation, resulting in insulin-independent glucose uptake.^ Metformin decreases hepatic glucose production, decreasing intestinal absorption of glucose, and improves insulin sensitivity (increases peripheral glucose uptake and utilization).

^ Resistance to the effects of insulin on glucose uptake and metabolism in skeletal muscle is a major contributor to the pathogenesis of insulin-resistant states, such as obesity and type 2 diabetes ( 1 , 2 ).
  • Troglitazone but not Metformin Restores Insulin-Stimulated Phosphoinositide 3-Kinase Activity and Increases p110β Protein Levels in Skeletal Muscle of Type 2 Diabetic Subjects — Diabetes 16 January 2010 3:50 UTC diabetes.diabetesjournals.org [Source type: Academic]

^ Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin.
  • Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes — Diabetes 16 January 2010 3:50 UTC diabetes.diabetesjournals.org [Source type: Academic]

Some metabolic actions of metformin do appear to occur by AMPK-independent mechanisms; a 2008 study found that "the metabolic actions of metformin in the heart muscle can occur independent of changes in AMPK activity and may be mediated by p38 MAPK- and PKC-dependent mechanisms."[106]

Interactions

.The H2-receptor antagonist cimetidine causes an increase in the plasma concentration of metformin, by reducing clearance of metformin by the kidneys;[107] both metformin and cimetidine are cleared from the body by tubular secretion, and both, particularly the cationic (positively charged) form of cimetidine, may compete for the same transport mechanism.^ The H 2 -receptor antagonist cimetidine causes an increase in the plasma concentration of metformin, by reducing clearance of metformin by the kidneys; [31] both metformin and cimetidine are cleared from the body by tubular secretion, and both, particularly the cationic (positively charged ) form of cimetidine, may compete for the same transport mechanism.
  • Metformin: Encyclopedia of chemistry, analytics & pharmaceutics with 64,557 entries. 16 January 2010 3:50 UTC www.chemie.de [Source type: Academic]

^ Cimetidine increases (by 60%) peak metformin plasma and whole blood concentrations .
  • Metformin - Erewhon Natural Foods 16 January 2010 3:50 UTC www.erewhonmarket.com [Source type: Academic]

^ The effect of metformin may be increased if you also take cimetidine (Tagamet).

[95] .A small double-blind, randomized study found the antibiotic cefalexin to also increase metformin concentrations by a similar mechanism;[108] theoretically, other cationic medications may produce the same effect.^ Study Design A double-blind, placebo-controlled randomized design was used.
  • Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study -- Wu et al. 165 (3): 352 -- Am J Psychiatry 16 January 2010 3:50 UTC ajp.psychiatryonline.org [Source type: Academic]

^ In the present study, rosiglitazone and metformin had similar effects on FFA concentrations.
  • Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes — Diabetes 16 January 2010 3:50 UTC diabetes.diabetesjournals.org [Source type: Academic]

^ The effect of metformin may be increased if you also take cimetidine (Tagamet).

[95]

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