Identification

Name
Metformin
Accession Number
DB00331
Description

Metformin is an antihyperglycemic agent of the biguanide class, used for the management of type II diabetes) Label. Currently, metformin is the first drug of choice for the management of type II diabetes and is prescribed to at least 120 million people worldwide 14.

Metformin is considered an antihyperglycemic drug because it lowers blood glucose concentrations in type II diabetes without causing hypoglycemia. Metformin is commonly described as an insulin sensitizer leading to a decrease in insulin resistance and a clinically significant reduction of plasma fasting insulin levels 14. Another well-known benefit of this drug is modest weight loss. Metformin is the drug of choice for obese type II diabetes patients 12.

Metformin was first approved in Canada in 1972 8, followed by 1995 in the USA Label. This drug is available in regular and extended-release forms Label.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 129.1636
Monoisotopic: 129.101445377
Chemical Formula
C4H11N5
Synonyms
  • 1,1-Dimethylbiguanide
  • Dimethylbiguanid
  • Metformin
  • Metformina
  • Metformine
  • Metforminum
External IDs
  • LA 6023
  • LA-6023

Pharmacology

Indication

Metformin tablet

Metformin is indicated as an adjunct to diet and exercise to increase glycemic control in adults and pediatric patients 10 years of age and older diagnosed with type 2 diabetes mellitus.Label

Metformin extended-release tablet (XR)

The extended-release form is indicated as an adjunct to diet and exercise to improve glycemic control in only adults with type 2 diabetes mellitus. Safety in children has not been determined to this date.Label

An extended-release combination product containing empagliflozin, linagliptin, and metformin was approved by the FDA in January 2020 for the improvement of glycemic control in adults with type 2 diabetes mellitus when used adjunctively with diet and exercise.22

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

General effects

Insulin is an important hormone that regulates blood glucose levels 19. Type II diabetes is characterized by a decrease in sensitivity to insulin, resulting in eventual elevations in blood glucose when the pancreas can no longer compensate. In patients diagnosed with type 2 diabetes, insulin no longer exerts adequate effects on tissues and cells (called insulin resistance) 19 and insulin deficiency may also be present 21.

Metformin reduces liver (hepatic) production of glucose, decreases the intestinal absorption of glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization. In contrast with drugs of the sulfonylurea class, which lead to hyperinsulinemia, the secretion of insulin is unchanged with metformin use Label.

Effect on fasting plasma glucose (FPG) and Glycosylated hemoglobin (HbA1c)

HbA1c is an important periodic measure of glycemic control that is used to monitor diabetic patients. Fasting plasma glucose is also a useful and important measure of glycemic control. In a 29-week clinical trial of subjects diagnosed with type II diabetes, metformin decreased the fasting plasma glucose levels by an average of 59 mg/dL from baseline, compared to an average increase of 6.3 mg/dL from baseline in subjects taking a placebo Label. Glycosylated hemoglobin (HbA1c) was decreased by about 1.4% in subjects receiving metformin, and increased by 0.4% in subjects receiving placebo only Label.

Mechanism of action

Metformin's mechanisms of action are unique from other classes of oral antihyperglycemic drugs. Metformin decreases blood glucose levels by decreasing hepatic glucose production (gluconeogenesis), decreasing the intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilization Label. It is well established that metformin inhibits mitochondrial complex I activity, and it has since been generally postulated that its potent antidiabetic effects occur through this mechanism 6,11. The above processes lead to a decrease in blood glucose, managing type II diabetes and exerting positive effects on glycemic control.

After ingestion, the organic cation transporter-1 (OCT1) is responsible for the uptake of metformin into hepatocytes (liver cells). As this drug is positively charged, it accumulates in cells and in the mitochondria because of the membrane potentials across the plasma membrane as well as the mitochondrial inner membrane. Metformin inhibits mitochondrial complex I, preventing the production of mitochondrial ATP leading to increased cytoplasmic ADP:ATP and AMP:ATP ratios 6. These changes activate AMP-activated protein kinase (AMPK), an enzyme that plays an important role in the regulation of glucose metabolism 15. Aside from this mechanism, AMPK can be activated by a lysosomal mechanism involving other activators. Following this process, increases in AMP:ATP ratio also inhibit fructose-1,6-bisphosphatase enzyme, resulting in the inhibition of gluconeogenesis, while also inhibiting adenylate cyclase and decreasing the production of cyclic adenosine monophosphate (cAMP) 6, a derivative of ATP used for cell signaling 16. Activated AMPK phosphorylates two isoforms of acetyl-CoA carboxylase enzyme, thereby inhibiting fat synthesis and leading to fat oxidation, reducing hepatic lipid stores and increasing liver sensitivity to insulin 6.

In the intestines, metformin increases anaerobic glucose metabolism in enterocytes (intestinal cells), leading to reduced net glucose uptake and increased delivery of lactate to the liver. Recent studies have also implicated the gut as a primary site of action of metformin and suggest that the liver may not be as important for metformin action in patients with type 2 diabetes. Some of the ways metformin may play a role on the intestines is by promoting the metabolism of glucose by increasing glucagon-like peptide I (GLP-1) as well as increasing gut utilization of glucose 6.

In addition to the above pathway, the mechanism of action of metformin may be explained by other ways, and its exact mechanism of action has been under extensive study in recent years 7,9,10,11.

TargetActionsOrganism
A5'-AMP-activated protein kinase subunit beta-1
inducer
activator
Humans
AElectron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
inhibitor
Humans
UGlycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic
inhibitor
Humans
Absorption

Regular tablet absorption

The absolute bioavailability of a metformin 500 mg tablet administered in the fasting state is about 50%-60%. Single-dose clinical studies using oral doses of metformin 500 to 1500 mg and 850 to 2550 mg show that there is a lack of dose proportionality with an increase in metformin dose, attributed to decreased absorption rather than changes in elimination Label.

At usual clinical doses and dosing schedules of metformin, steady-state plasma concentrations of metformin are achieved within 24-48 hours and are normally measured at <1 μg/mL Label.

Extended-release tablet absorption

After a single oral dose of metformin extended-release, Cmax is reached with a median value of 7 hours and a range of between 4 and 8 hours. Peak plasma levels are measured to be about 20% lower compared to the same dose of regular metformin, however, the extent of absorption of both forms (as measured by area under the curve - AUC), are similar Label.

Effect of food

Food reduces the absorption of metformin, as demonstrated by about a 40% lower mean peak plasma concentration (Cmax), a 25% lower area under the plasma concentration versus time curve (AUC), and a 35-minute increase in time to peak plasma concentration (Tmax) after ingestion of an 850 mg tablet of metformin taken with food, compared to the same dose administered during fasting Label.

Though the extent of metformin absorption (measured by the area under the curve - AUC) from the metformin extended-release tablet is increased by about 50% when given with food, no effect of food on Cmax and Tmax of metformin is observed. High and low-fat meals exert similar effects on the pharmacokinetics of extended-release metformin Label.

Volume of distribution

The apparent volume of distribution (V/F) of metformin after one oral dose of metformin 850 mg averaged at 654 ± 358 L Label.

Protein binding

Metformin is negligibly bound to plasma proteins Label, in contrast to sulfonylureas, which are more than 90% protein bound 13.

Metabolism

Intravenous studies using a single dose of metformin in normal subjects show that metformin is excreted as unchanged drug in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) or biliary excretion Label.

Route of elimination

This drug is substantially excreted by the kidney Label.

Renal clearance of metformin is about 3.5 times higher than creatinine clearance, which shows that renal tubular secretion is the major route of metformin elimination. After oral administration, about 90% of absorbed metformin is eliminated by the kidneys within the first 24 hours post-ingestion Label.

Half-life

Approximately 6.2 hours in the plasma Label and in the blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution Label.

Clearance

Renal clearance is about 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours Label.

Adverse Effects
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Toxicity

Metformin (hydrochloride) toxicity data:

Oral LD50 (rat): 1 g/kg; Intraperitoneal LD50 (rat): 500 mg/kg; Subcutaneous LD50 (rat): 300 mg/kg; Oral LD50 (mouse): 1450 mg/kg; Intraperitoneal LD50 (mouse): 420 mg/kg; Subcutaneous LD50 (mouse): 225 mg/kg MSDS.

A note on lactic acidosis

Metformin decreases liver uptake of lactate, thereby increasing lactate blood levels which may increase the risk of lactic acidosis Label. There have been reported postmarketing cases of metformin-associated lactic acidosis, including some fatal cases. Such cases had a subtle onset and were accompanied by nonspecific symptoms including malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence. In certain cases, hypotension and resistant bradyarrhythmias have occurred with severe lactic acidosis Label. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), as well as an increased lactate:pyruvate ratio; metformin plasma levels were generally >5 mcg/mLLabel.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment Label.

A note on renal function

In patients with decreased renal function, the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased Label.

Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis Label. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels.

A note on hypoglycemia

When used alone, metformin does not cause hypoglycemia, however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin when they are used together Label.

Use in pregnancy

Available data from post-marketing studies have not indicated a clear association of metformin with major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was ingested during pregnancy. Despite this, the abovementioned studies cannot definitively establish the absence of any metformin-associated risk due to methodological limitations, including small sample size and inconsistent study groups Label.

Use in nursing

A limited number of published studies indicate that metformin is present in human milk. There is insufficient information to confirm the effects of metformin on the nursing infant and no available data on the effects of metformin on the production of milk. The developmental and health benefits of breastfeeding should be considered as well as the mother’s clinical need for metformin and any possible adverse effects on the nursing child Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMetformin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Metformin.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Metformin.
AcebutololThe therapeutic efficacy of Metformin can be increased when used in combination with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Metformin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Metformin which could result in a higher serum level.
AcetazolamideThe risk or severity of lactic acidosis can be increased when Acetazolamide is combined with Metformin.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Metformin is combined with Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Metformin can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidThe risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Metformin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol.
  • Take with food. Food reduces irritation.

Products

Product Ingredients
IngredientUNIICASInChI Key
Metformin hydrochloride786Z46389E1115-70-4OETHQSJEHLVLGH-UHFFFAOYSA-N
Product Images
International/Other Brands
Apo-Metformin (Apotex) / Gen-Metformin (Genpharm ULC) / Novo-Metformin (Novopharm) / Nu-Metformin (Nu-Pharm) / Sandoz Metformin (Sandox)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Acc-metforminTabletOralAccel Pharma IncNot applicableNot applicableCanada flag
Act MetforminTabletOralTEVA Canada Limited2004-11-05Not applicableCanada flag
Act MetforminTabletOralTEVA Canada Limited2004-11-05Not applicableCanada flag
Bci MetforminTabletOralBaker Cummins Inc2005-04-072006-10-03Canada flag
Bci MetforminTabletOralBaker Cummins Inc2005-07-042006-10-03Canada flag
FortametTablet, extended release1000 mg/1OralPhysicians Total Care, Inc.2010-02-18Not applicableUS flag59630 0575 60 nlmimage10 9707cb9e
FortametTablet, film coated, extended release500 mg/1OralSHIONOGI INC.2004-04-27Not applicableUS flag
FortametTablet, extended release500 mg/1OralPhysicians Total Care, Inc.2006-03-24Not applicableUS flag
FortametTablet, film coated, extended release1000 mg/1OralSHIONOGI INC.2004-04-27Not applicableUS flag
GlucophageTablet, film coated850 mg/1OralBristol-Myers Squibb Company2009-06-012020-07-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-metforminTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Ag-metforminTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-metformin - Tab 500mgTabletOralApotex Corporation1995-12-31Not applicableCanada flag
Apo-metformin 850 Mg TabletsTabletOralApotex Corporation1996-11-20Not applicableCanada flag
Apo-metformin ERTablet, extended releaseOralApotex Corporation2018-05-14Not applicableCanada flag
Apo-metformin ERTablet, extended releaseOralApotex Corporation2017-10-02Not applicableCanada flag
Auro-metforminTabletOralAuro Pharma Inc2015-04-08Not applicableCanada flag
Auro-metforminTabletOralAuro Pharma Inc2015-04-08Not applicableCanada flag
Ava-metforminTabletOralAvanstra Inc2011-09-152014-08-21Canada flag
Ava-metforminTabletOralAvanstra Inc2011-09-152014-08-21Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Actoplus MetMetformin hydrochloride (850 mg/1) + Pioglitazone hydrochloride (15 mg/1)Tablet, film coatedOralTakeda Pharmaceuticals America, Inc.2005-08-29Not applicableUS flag
Actoplus MetMetformin hydrochloride (850 mg/1) + Pioglitazone hydrochloride (15 mg/1)Tablet, film coatedOralCardinal Health2005-08-292014-05-31US flag
Actoplus MetMetformin hydrochloride (500 mg/1) + Pioglitazone hydrochloride (15 mg/1)Tablet, film coatedOralTakeda Pharmaceuticals America, Inc.2005-08-29Not applicableUS flag
Actoplus MetMetformin hydrochloride (850 mg/1) + Pioglitazone hydrochloride (15 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-03-21Not applicableUS flag
Actoplus MetMetformin hydrochloride (500 mg/1) + Pioglitazone hydrochloride (15 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-01-04Not applicableUS flag
Actoplus Met XRMetformin hydrochloride (1000 mg/1) + Pioglitazone hydrochloride (30 mg/1)Tablet, film coated, extended releaseOralTakeda Pharmaceuticals America, Inc.2010-06-112022-09-30US flag
Actoplus Met XRMetformin hydrochloride (1000 mg/1) + Pioglitazone hydrochloride (15 mg/1)Tablet, film coated, extended releaseOralTakeda Pharmaceuticals America, Inc.2010-06-112022-09-30US flag
Alogliptin and Metformin HydrochlorideMetformin hydrochloride (500 mg/1) + Alogliptin benzoate (12.5 mg/1)Tablet, film coatedOralPerrigo New York Inc2016-04-08Not applicableUS flag
Alogliptin and Metformin HydrochlorideMetformin hydrochloride (1000 mg/1) + Alogliptin benzoate (12.5 mg/1)Tablet, film coatedOralPerrigo New York Inc2016-04-08Not applicableUS flag
AvandametMetformin hydrochloride (500 mg/1) + Rosiglitazone Maleate (4 mg/1)Tablet, film coatedOralGlaxosmithkline Inc2011-05-242015-11-06US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AppforminMetformin hydrochloride (500 mg/1) + Tyrosine (100 mg/1)KitOralPhysician Therapeutics Llc2011-02-07Not applicableUS flag
Appformin-DMetformin hydrochloride (500 mg/1) + Tyrosine (100 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUS flag

Categories

ATC Codes
A10BD23 — Metformin and ertugliflozinA10BD02 — Metformin and sulfonylureasA10BD18 — Metformin and gemigliptinA10BD11 — Metformin and linagliptinA10BD25 — Metformin, saxagliptin and dapagliflozinA10BA02 — MetforminA10BD22 — Metformin and evogliptinA10BD14 — Metformin and repaglinideA10BD16 — Metformin and canagliflozinA10BD17 — Metformin and acarboseA10BD05 — Metformin and pioglitazoneA10BD15 — Metformin and dapagliflozinA10BD07 — Metformin and sitagliptinA10BD10 — Metformin and saxagliptinA10BD13 — Metformin and alogliptinA10BD20 — Metformin and empagliflozinA10BD08 — Metformin and vildagliptinA10BD03 — Metformin and rosiglitazone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as biguanides. These are organic compounds containing two N-linked guanidines.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Guanidines
Direct Parent
Biguanides
Alternative Parents
Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Organopnictogen compounds / Imines / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Biguanide / Carboximidamide / Hydrocarbon derivative / Imine / Organic 1,3-dipolar compound / Organopnictogen compound / Propargyl-type 1,3-dipolar organic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
guanidines (CHEBI:6801)

Chemical Identifiers

UNII
9100L32L2N
CAS number
657-24-9
InChI Key
XZWYZXLIPXDOLR-UHFFFAOYSA-N
InChI
InChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
IUPAC Name
1-carbamimidamido-N,N-dimethylmethanimidamide
SMILES
CN(C)C(=N)NC(N)=N

References

Synthesis Reference

Jorn Moeckel, Rolf-Dieter Gabel, Heinrich Woog, "Pharmaceutical preparation containing metformin and a process for producing it." U.S. Patent US5955106, issued October, 1991.

US5955106
General References
  1. Witters LA: The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7. [PubMed:11602616]
  2. UNGAR G, FREEDMAN L, SHAPIRO SL: Pharmacological studies of a new oral hypoglycemic drug. Proc Soc Exp Biol Med. 1957 May;95(1):190-2. [PubMed:13432032]
  3. Lord JM, Flight IH, Norman RJ: Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003 Oct 25;327(7421):951-3. [PubMed:14576245]
  4. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N: Metformin in non-alcoholic steatohepatitis. Lancet. 2001 Sep 15;358(9285):893-4. [PubMed:11567710]
  5. Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP: Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004 Jul 1;20(1):23-8. [PubMed:15225167]
  6. Rena G, Hardie DG, Pearson ER: The mechanisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-1585. doi: 10.1007/s00125-017-4342-z. Epub 2017 Aug 3. [PubMed:28776086]
  7. Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, Camporez JG, Cline GW, Butrico GM, Kemp BE, Casals G, Steinberg GR, Vatner DF, Petersen KF, Shulman GI: Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat Med. 2018 Jul 23. pii: 10.1038/s41591-018-0125-4. doi: 10.1038/s41591-018-0125-4. [PubMed:30038219]
  8. Lucis OJ: The status of metformin in Canada. Can Med Assoc J. 1983 Jan 1;128(1):24-6. [PubMed:6847752]
  9. Cameron AR, Logie L, Patel K, Erhardt S, Bacon S, Middleton P, Harthill J, Forteath C, Coats JT, Kerr C, Curry H, Stewart D, Sakamoto K, Repiscak P, Paterson MJ, Hassinen I, McDougall G, Rena G: Metformin selectively targets redox control of complex I energy transduction. Redox Biol. 2018 Apr;14:187-197. doi: 10.1016/j.redox.2017.08.018. Epub 2017 Aug 26. [PubMed:28942196]
  10. Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI: Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014 Jun 26;510(7506):542-6. doi: 10.1038/nature13270. Epub 2014 May 21. [PubMed:24847880]
  11. Rena G, Pearson ER, Sakamoto K: Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013 Sep;56(9):1898-906. doi: 10.1007/s00125-013-2991-0. Epub 2013 Jul 9. [PubMed:23835523]
  12. Lund SS, Tarnow L, Stehouwer CD, Schalkwijk CG, Frandsen M, Smidt UM, Pedersen O, Parving HH, Vaag A: Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial. Diabetes Obes Metab. 2007 May;9(3):394-407. doi: 10.1111/j.1463-1326.2007.00713.x. [PubMed:17391168]
  13. Proks P, Kramer H, Haythorne E, Ashcroft FM: Binding of sulphonylureas to plasma proteins - A KATP channel perspective. PLoS One. 2018 May 17;13(5):e0197634. doi: 10.1371/journal.pone.0197634. eCollection 2018. [PubMed:29772022]
  14. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F: Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012 Mar;122(6):253-70. doi: 10.1042/CS20110386. [PubMed:22117616]
  15. Misra P, Chakrabarti R: The role of AMP kinase in diabetes. Indian J Med Res. 2007 Mar;125(3):389-98. [PubMed:17496363]
  16. Valsecchi F, Ramos-Espiritu LS, Buck J, Levin LR, Manfredi G: cAMP and mitochondria. Physiology (Bethesda). 2013 May;28(3):199-209. doi: 10.1152/physiol.00004.2013. [PubMed:23636265]
  17. Misbin RI: The phantom of lactic acidosis due to metformin in patients with diabetes. Diabetes Care. 2004 Jul;27(7):1791-3. doi: 10.2337/diacare.27.7.1791. [PubMed:15220268]
  18. Matthew J Crowley, MD, Clarissa J Diamantidis, MD, Jennifer R McDuffie, PhD, Blake Cameron, MD, John Stanifer, MD, Clare K Mock, MD, Andrzej Kosinski, PhD, Xianwei Wang, MD, Shuang Tang, MD, PhD, and John W Williams, Jr, MD, MHSc (2016). Metformin Use in Patients with Historical Contraindications or Precautions. Department of Veterans Affairs (US).
  19. Institute for Quality and Efficiency in Health Care (IQWiG) (2008). Type 2 diabetes: Overview. InformedHealth.org.
  20. Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program [Link]
  21. UptoDate: Pathogenesis of type 2 diabetes mellitus [Link]
  22. FDA Approved Drug Products: Trijardy XR (empagliflozin/linagliptin/metformin) extended-release tablets [Link]
  23. FDA approved products: Glumetza (metformin) oral tablets [Link]
  24. Comparing Dissolution Profiles of of Seven Metformin Formulations in Simulated Intestinal Fluid [File]
  25. Glumetza FDA [File]
  26. Metformin label [File]
  27. Metformin Canadian monograph [File]
  28. MedSafe NZ Metformin mylan [File]
Human Metabolome Database
HMDB0001921
KEGG Drug
D04966
KEGG Compound
C07151
PubChem Compound
4091
PubChem Substance
46507752
ChemSpider
3949
BindingDB
50229665
RxNav
6809
ChEBI
6801
ChEMBL
CHEMBL1431
ZINC
ZINC000012859773
Therapeutic Targets Database
DAP000205
PharmGKB
PA450395
PDBe Ligand
MF8
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Metformin
AHFS Codes
  • 68:20.04 — Biguanides
PDB Entries
5g5j
FDA label
Download (329 KB)
MSDS
Download (23.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionMountain Sickness1
4Active Not RecruitingPreventionPre-Diabetic1
4Active Not RecruitingTreatmentAtherosclerosis / Coronary Artery Disease (CAD) / Prediabetic State1
4Active Not RecruitingTreatmentAtherosclerosis / Metformin / Novel Coronavirus Infectious Disease (COVID-19) / Prediabetic State1
4Active Not RecruitingTreatmentDiabetes1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1) Infection / Pre-Diabetic1
4Active Not RecruitingTreatmentImpaired Fasting Glucose (IFG) / Impaired Glucose Tolerance / Pre-Diabetic1
4Active Not RecruitingTreatmentType 1 Diabetes Mellitus1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus4
4CompletedNot AvailableAmenorrhea1

Pharmacoeconomics

Manufacturers
  • Ranbaxy pharmaceuticals inc
  • Andrx labs llc
  • Bristol myers squibb co
  • Depomed inc
  • Actavis elizabeth llc
  • Amneal pharmaceuticals ny llc
  • Apotex inc etobicoke site
  • Barr laboratories inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Neurosci inc
  • Nostrum pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Torrent pharma inc
  • Torrent pharmaceuticals ltd
  • Watson laboratories inc
  • Watson laboratories inc florida
  • Zydus pharmaceuticals usa inc
  • Bristol myers squibb co pharmaceutical research institute
  • Alphapharm party ltd
  • Alvogen inc
  • Apotex inc
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Dr reddys laboratories inc
  • Genpharm inc
  • Glenmark generics ltd
  • Granules india ltd
  • Indicus pharma llc
  • Ipca laboratories ltd
  • Mutual pharmacal co
  • Provident pharmaceutical inc
  • Watson laboratories
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Alphapharm Party Ltd.
  • Amerisource Health Services Corp.
  • Amkas Laboratories Inc.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • Apotheca Inc.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Aurolife Pharma LLC
  • Barr Pharmaceuticals
  • Biovail Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Cadila Healthcare Ltd.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Caremark LLC
  • Cobalt Pharmaceuticals Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Depomed Inc.
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • DSM Corp.
  • Emcure Pharmaceuticals Ltd.
  • Eon Labs
  • Glenmark Generics Ltd.
  • Golden State Medical Supply Inc.
  • Greenstone LLC
  • Heartland Repack Services LLC
  • Heritage Pharmaceuticals
  • Indicus Pharma LLC
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Legacy Pharmaceuticals Packaging LLC
  • Liberty Pharmaceuticals
  • Lipha Pharmaceuticals Ltd.
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • Medisca Inc.
  • Medvantx Inc.
  • Merck KGaA
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Neurosci Inc.
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Ohm Laboratories Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Provident Pharmaceuticals LLC
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandoz
  • Sciele Pharma Inc.
  • Solco Healthcare US LLC
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Stat Scripts LLC
  • Sun Pharmaceutical Industries Ltd.
  • Takeda Pharmaceutical Co. Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Torrent Pharmaceuticals
  • Tya Pharmaceuticals
  • UDL Laboratories
  • USV Ltd.
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, film coatedOral15 mg
Tablet850 mg
Tablet, coatedOral1 mg
Tablet, coatedOral4 mg
Tablet, extended releaseOral2 mg
Tablet, extended releaseOral850 mg
KitOral
Tablet1 g
Tablet, film coatedOral1000 MG
Tablet, film coatedOral500 MG
Tablet, film coatedOral850 MG
Tablet, film coated1000 mg
Tablet, film coated850 mg
Tablet
TabletOral750 mg
TabletOral5 MG
KitOral500 mg/1
TabletOral80 mg
Tablet, coatedOral250 mg
Tablet, extended releaseOral
SolutionOral10 g
Tablet, coatedOral500 mg
Tablet, coatedOral1000 mg
Tablet, coatedOral400 MG
TabletOral2.5 mg
Tablet, coatedOral15 mg
Tablet, extended releaseOral15 mg
Tablet, delayed releaseOral30 mg
Tablet, extended release1000 mg
Tablet, extended release500 mg
Tablet, coatedOral850 mg
Tablet, effervescentOral15 mg
Tablet, effervescentOral30 mg
TabletOral
Tablet, coatedOral
Tablet80 mg
TabletOral15 MG
Powder, for solutionOral1000 MG
Powder, for solutionOral500 MG
Powder, for solutionOral850 MG
Tablet, coatedOral1 g
Tablet, extended releaseOral500 mg
Tablet, extended releaseOral750 mg
Tablet, film coated500 mg
Tablet, extended releaseOral1 g
Tablet, coatedOral1.25 mg
Tablet, coatedOral5 mg
Tablet, film coated, extended releaseOral1000 mg/1
Tablet, film coated, extended releaseOral500 mg/1
Powder
Tablet, coatedOral50 mg
Tablet, delayed releaseOral1000 mg
Tablet, film coatedOral12.5 mg
Tablet, film coated, extended releaseOral
Tablet, extended releaseOral1000 mg
Tablet, film coatedOral
Tablet, coatedOral2.5 mg
Tablet500 mg
Tablet, effervescentOral100 mg
TabletNot applicable1000 mg/1
TabletNot applicable500 mg/1
TabletNot applicable850 mg/1
TabletOral1000 mg/1
TabletOral500 mg/1
TabletOral850 mg/1
Tablet, coatedOral1000 mg/1
Tablet, coatedOral500 mg/1
Tablet, coatedOral850 mg/1
Tablet, extended releaseOral1000 mg/1
Tablet, extended releaseOral500 mg/1
Tablet, extended releaseOral750 mg/1
Tablet, extended releaseOral850 mg/1
Tablet, film coatedOral1000 mg/1
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral850 mg/1
TabletOral750 mg/1
TabletOral1000 MG
TabletOral500 MG
Tablet, coated1000 MG
Tablet, coated500 MG
Tablet, coated850 MG
Tablet, film coatedOral2.5 mg
Tablet, effervescent1000 mg
Tablet, effervescent500 mg
Tablet, effervescent850 mg
Tablet, coatedOral2 mg
Tablet, delayed release1000 mg
Tablet, delayed release500 mg
TabletOral850 mg
TabletOral120 mg
Tablet, film coatedOral120 mg
Tablet, film coatedOral180 mg
Tablet, coatedOral30 mg
Tablet, effervescentOral1 mg
Tablet, effervescentOral2 mg
SolutionOral500 mg/5mL
For suspension, extended releaseOral500 mg/5mL
Tablet, film coatedOral7.5 MG
Tablet, film coated
Tablet, coatedOral12.5 mg
Tablet, extended releaseOral
TabletOral
Tablet, film coatedOral
Tablet, coated50 mg
Tablet, film coatedOral150 mg
Tablet, coatedOral150 mg
Tablet, film coatedOral50 mg
Tablet, film coatedOral5 MG
Tablet, extended releaseOral10 mg
Tablet, coatedOral10 mg
Tablet, extended releaseOral1005.04 mg
Tablet, extended releaseOral5 mg
Prices
Unit descriptionCostUnit
Fortamet er 1000 mg tablet6.93USD tablet
Fortamet 1000 mg 24 Hour tablet6.01USD tablet
Fortamet 500 mg 24 Hour tablet2.55USD tablet
Fortamet er 500 mg tablet2.48USD tablet
Glucophage 1000 mg tablet2.33USD tablet
Metformin hcl crystals2.14USD g
Glucophage 850 mg tablet1.94USD tablet
Glucophage XR 750 mg 24 Hour tablet1.8USD tablet
Glucophage xr 750 mg tablet1.71USD tablet
Metformin hcl 1000 mg tablet1.48USD tablet
MetFORMIN HCl 750 mg 24 Hour tablet1.25USD tablet
Metformin hcl 850 mg tablet1.22USD tablet
Glucophage XR 500 mg 24 Hour tablet1.17USD tablet
Glucophage 500 mg tablet1.14USD tablet
Glucophage xr 500 mg tablet1.14USD tablet
Glucophage xr 500 mg tablet sa1.11USD tablet
MetFORMIN HCl 500 mg 24 Hour tablet0.75USD tablet
Metformin hcl 500 mg tablet0.72USD tablet
Glucophage 850 mg Tablet0.38USD tablet
Glucophage 500 mg Tablet0.3USD tablet
Riomet 500 mg/5 ml solution0.27USD ml
Riomet 500 mg/5ml Solution0.27USD ml
Apo-Metformin 850 mg Tablet0.21USD tablet
Co Metformin 850 mg Tablet0.21USD tablet
Mylan-Metformin 850 mg Tablet0.21USD tablet
Novo-Metformin 850 mg Tablet0.21USD tablet
Nu-Metformin 850 mg Tablet0.21USD tablet
Pms-Metformin 850 mg Tablet0.21USD tablet
Ratio-Metformin Hydrochloride 850 mg Tablet0.21USD tablet
Sandoz Metformin Fc 850 mg Tablet0.21USD tablet
Pms-Metformin 500 mg Tablet0.13USD tablet
Ran-Metformin 500 mg Tablet0.13USD tablet
Ratio-Metformin Hydrochloride 500 mg Tablet0.13USD tablet
Sandoz Metformin Fc 500 mg Tablet0.13USD tablet
Zym-Metformin 500 mg Tablet0.13USD tablet
Apo-Metformin 500 mg Tablet0.13USD tablet
Co Metformin 500 mg Tablet0.13USD tablet
Mylan-Metformin 500 mg Tablet0.13USD tablet
Novo-Metformin 500 mg Tablet0.13USD tablet
Nu-Metformin 500 mg Tablet0.13USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2476496No2009-12-152023-02-21Canada flag
CA2412671No2006-10-032021-02-26Canada flag
US7326708No2008-02-052026-04-11US flag
US7407955No2008-08-052023-08-12US flag
US6150383No2000-11-212016-06-19US flag
US6211205No2001-04-032016-06-19US flag
US6303640No2001-10-162016-08-09US flag
US6329404No2001-12-112016-06-19US flag
US6699871No2004-03-022022-07-26US flag
US7125873No2006-10-242022-07-26US flag
US5965584No1999-10-122016-06-19US flag
US6166042No2000-12-262016-06-19US flag
US6166043No2000-12-262016-06-19US flag
US6172090No2001-01-092016-06-19US flag
US6790459No2004-09-142021-03-17US flag
US7919116No2011-04-052018-03-20US flag
US8475841No2013-07-022018-03-20US flag
US6099859No2000-08-082018-03-20US flag
US6866866No2005-03-152021-03-17US flag
US7785627No2010-08-312026-07-31US flag
US7959946No2011-06-142026-07-31US flag
US8470368No2013-06-252023-09-19US flag
US8668931No2014-03-112023-09-19US flag
US9060941No2015-06-232023-09-19US flag
US6495162No2002-12-172018-03-20US flag
US8414921No2013-04-092028-07-21US flag
US6288095Yes2001-09-112017-08-11US flag
US7358366Yes2008-04-152020-10-19US flag
US6150384No2000-11-212016-06-19US flag
US6303146Yes2001-10-162020-01-14US flag
US6660300No2003-12-092018-03-19US flag
US6475521No2002-11-052018-03-19US flag
US8236345No2012-08-072022-10-07US flag
US6890957No2005-05-102023-09-14US flag
US6340475No2002-01-222016-09-19US flag
US6635280No2003-10-212016-09-19US flag
US6488962No2002-12-032020-06-20US flag
US7780987No2010-08-242025-03-23US flag
US8323692No2012-12-042025-03-23US flag
US6723340No2004-04-202021-10-25US flag
US9101660No2015-08-112027-01-22US flag
US6303661No2001-10-162017-04-24US flag
US6890898No2005-05-102019-02-02US flag
US7078381No2006-07-182019-02-02US flag
US7459428No2008-12-022019-02-02US flag
US7807689No2010-10-052028-06-27US flag
US8173663No2012-05-082025-03-15US flag
US8288539No2012-10-162025-03-15US flag
USRE44186No2013-04-302023-07-31US flag
US8119648No2012-02-212023-08-12US flag
US8178541No2012-05-152023-08-12US flag
US8846695No2014-09-302030-06-04US flag
US9173859No2015-11-032027-05-04US flag
US8673927No2014-03-182027-05-04US flag
US8883805No2014-11-112025-11-26US flag
US9155705No2015-10-132030-05-21US flag
US8628799No2014-01-142025-07-13US flag
US8900638No2014-12-022029-05-24US flag
US8222219No2012-07-172024-07-30US flag
US8513202No2013-08-202027-12-03US flag
US7943582No2011-05-172029-02-26US flag
US8785403No2014-07-222024-07-30US flag
US7943788No2011-05-172027-07-14US flag
US8685934No2014-04-012030-05-26US flag
US8501698No2013-08-062027-06-20US flag
US6414126No2002-07-022020-10-04US flag
US6515117No2003-02-042020-10-04US flag
US6936590No2005-08-302020-10-04US flag
US9198925No2015-12-012020-10-04US flag
US7919598No2011-04-052029-12-16US flag
US8716251No2014-05-062028-03-21US flag
US8551957No2013-10-082029-10-19US flag
US7713938No2010-05-112027-04-15US flag
US7579449No2009-08-252025-11-05US flag
US9320714No2016-04-262029-02-03US flag
US9415016No2016-08-162029-04-02US flag
US9339472No2016-05-172025-07-13US flag
US9555001No2017-01-312033-03-06US flag
US9616028No2017-04-112030-11-12US flag
US8080580No2011-12-202030-07-13US flag
US9439902No2016-09-132030-10-21US flag
US9308204No2016-04-122030-10-21US flag
US9949998No2018-04-242034-06-11US flag
US10022379No2018-07-172029-04-02US flag
US10258637No2019-04-162034-04-03US flag
US10406172No2019-09-102030-06-15US flag
US9962336No2018-05-082035-05-01US flag
US10596120No2012-03-072032-03-07US flag
US10610489No2010-09-302030-09-30US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)223-226 °Chttp://www.molbase.com/en/properties_1115-70-4-moldata-22670.html
boiling point (°C)224.1ºC at 760 mmHghttp://www.molbase.com/en/properties_1115-70-4-moldata-22670.html
water solubility2g of metformin hydrochloride is soluble in 10mL of waterFDA label
logP-2.6https://www.sciencedirect.com/science/article/pii/S1319016413001229
pKa12.4FDA label
Predicted Properties
PropertyValueSource
Water Solubility1.38 mg/mLALOGPS
logP-1.8ALOGPS
logP-0.92ChemAxon
logS-2ALOGPS
pKa (Strongest Basic)12.33ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area88.99 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity56.64 m3·mol-1ChemAxon
Polarizability13.43 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.5868
Caco-2 permeable-0.8958
P-glycoprotein substrateNon-substrate0.6643
P-glycoprotein inhibitor INon-inhibitor0.9613
P-glycoprotein inhibitor IINon-inhibitor0.8892
Renal organic cation transporterNon-inhibitor0.7518
CYP450 2C9 substrateNon-substrate0.7929
CYP450 2D6 substrateNon-substrate0.7325
CYP450 3A4 substrateNon-substrate0.6906
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9159
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.913
CYP450 3A4 inhibitorNon-inhibitor0.9506
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9763
Ames testNon AMES toxic0.7367
CarcinogenicityNon-carcinogens0.6691
BiodegradationNot ready biodegradable0.938
Rat acute toxicity1.7407 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9807
hERG inhibition (predictor II)Non-inhibitor0.9274
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)LC-MS/MSsplash10-001i-0900000000-9046e2aa0408a0396007
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)LC-MS/MSsplash10-01qi-9700000000-a6b98d87cc840a082179
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)LC-MS/MSsplash10-00dr-9000000000-8e80f301bad045540477
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, PositiveLC-MS/MSsplash10-001i-0900000000-bd8aed328c944acd1270
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, PositiveLC-MS/MSsplash10-03l9-9300000000-3d585674ffe84238e5bf
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, PositiveLC-MS/MSsplash10-00di-9000000000-ee68820579ebe4d31082
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, PositiveLC-MS/MSsplash10-00di-9000000000-4312e7e5e1b0dd9ef936
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, PositiveLC-MS/MSsplash10-00di-9000000000-053d63fe09a95fc1d544
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0229-9100000000-7fe999a9d1aaae3bbe53
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-c235cd5d0dda3f3c28d9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0900000000-0fa445716bfc24131a75
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-3900000000-dee37da326e6f0b2c56a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0900000000-45bd1f8c6d2dc4f38944
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1900000000-38f3dedb5c19900cdefb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-7900000000-bf5d1092aa372c303d61
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03l9-9300000000-06a99f0dff4b41a23cfa
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-022i-9100000000-811c9e7cf8b30b27c0f2
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-9000000000-d34b9b3ab9eb78317eba
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0900000000-4d53ac0f7dfaf860e784
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1900000000-4b3dd439b62cfa2341b0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-6900000000-c595d8e83955ee66df73
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03l9-9300000000-1feb1004b70a7c1f7679
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-022i-9100000000-588dd4672e983d25189b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-9000000000-fdc1342fbdd0301080c8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-3900000000-f3959910a3d1ce1d1379
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03e9-9400000000-8fb5bd0de13e43cd9f9d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0229-9000000000-c5ee1ab43a4feb174be3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fu-9000000000-47265a863ca46a89f907
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0900000000-bd8aed328c944acd1270
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03l9-9300000000-3731f8e1b241c81f11e7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9000000000-ee68820579ebe4d31082
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9000000000-4312e7e5e1b0dd9ef936
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-9000000000-a112b8bb95bd75e1ce02
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-008i-8900000000-043e7607037d942cc570
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dr-9100000000-def4e48e0953ae8f3442
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-9100000000-2d692211680a93c2054e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-9100000000-49305dce40b0f4453fc4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03e9-9400000000-f625291fda51aa198464
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inducer
Activator
General Function
Protein kinase activity
Specific Function
Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellul...
Gene Name
PRKAB1
Uniprot ID
Q9Y478
Uniprot Name
5'-AMP-activated protein kinase subunit beta-1
Molecular Weight
30382.085 Da
References
  1. Kovacic S, Soltys CL, Barr AJ, Shiojima I, Walsh K, Dyck JR: Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem. 2003 Oct 10;278(41):39422-7. Epub 2003 Jul 29. [PubMed:12890675]
  2. Hardie DG: Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology. 2003 Dec;144(12):5179-83. Epub 2003 Sep 4. [PubMed:12960015]
  3. Ruderman NB, Saha AK, Kraegen EW: Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity. Endocrinology. 2003 Dec;144(12):5166-71. Epub 2003 Sep 18. [PubMed:14500570]
  4. Leverve XM, Guigas B, Detaille D, Batandier C, Koceir EA, Chauvin C, Fontaine E, Wiernsperger NF: Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S88-94. [PubMed:14502105]
  5. Leclerc I, Woltersdorf WW, da Silva Xavier G, Rowe RL, Cross SE, Korbutt GS, Rajotte RV, Smith R, Rutter GA: Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E1023-31. Epub 2004 Feb 10. [PubMed:14871885]
  6. Vucicevic L, Misirkic M, Janjetovic K, Harhaji-Trajkovic L, Prica M, Stevanovic D, Isenovic E, Sudar E, Sumarac-Dumanovic M, Micic D, Trajkovic V: AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C. Biochem Pharmacol. 2009 Jun 1;77(11):1684-93. doi: 10.1016/j.bcp.2009.03.005. Epub 2009 Mar 14. [PubMed:19428322]
  7. Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41. [PubMed:17307971]
  8. Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ: Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002 Jul;51(7):2074-81. [PubMed:12086935]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquinone binding
Specific Function
Accepts electrons from ETF and reduces ubiquinone.
Gene Name
ETFDH
Uniprot ID
Q16134
Uniprot Name
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
Molecular Weight
68494.96 Da
References
  1. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F: Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012 Mar;122(6):253-70. doi: 10.1042/CS20110386. [PubMed:22117616]
  2. Fontaine E: Metformin-Induced Mitochondrial Complex I Inhibition: Facts, Uncertainties, and Consequences. Front Endocrinol (Lausanne). 2018 Dec 17;9:753. doi: 10.3389/fendo.2018.00753. eCollection 2018. [PubMed:30619086]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nad binding
Specific Function
Not Available
Gene Name
GPD1
Uniprot ID
P21695
Uniprot Name
Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic
Molecular Weight
37567.4 Da
References
  1. Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI: Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014 Jun 26;510(7506):542-6. doi: 10.1038/nature13270. Epub 2014 May 21. [PubMed:24847880]
  2. Baur JA, Birnbaum MJ: Control of gluconeogenesis by metformin: does redox trump energy charge? Cell Metab. 2014 Aug 5;20(2):197-9. doi: 10.1016/j.cmet.2014.07.013. [PubMed:25100057]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM: Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2). Pharm Res. 2002 Aug;19(8):1244-7. [PubMed:12240953]
  2. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y: Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. [PubMed:12130709]
  3. Zolk O: Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther. 2009 Dec;86(6):595-8. doi: 10.1038/clpt.2009.144. [PubMed:19915604]
  4. Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, Sabolic I, Koepsell H, Brockmoller J: The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther. 2009 Sep;86(3):299-306. doi: 10.1038/clpt.2009.92. Epub 2009 Jun 17. [PubMed:19536068]
  5. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [PubMed:18788725]
  6. Pakkir Maideen NM, Jumale A, Balasubramaniam R: Drug Interactions of Metformin Involving Drug Transporter Proteins. Adv Pharm Bull. 2017 Dec;7(4):501-505. doi: 10.15171/apb.2017.062. Epub 2017 Dec 31. [PubMed:29399540]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Dresser MJ, Xiao G, Leabman MK, Gray AT, Giacomini KM: Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2). Pharm Res. 2002 Aug;19(8):1244-7. [PubMed:12240953]
  2. Zolk O: Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther. 2009 Dec;86(6):595-8. doi: 10.1038/clpt.2009.144. [PubMed:19915604]
  3. Kimura N, Masuda S, Tanihara Y, Ueo H, Okuda M, Katsura T, Inui K: Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86. [PubMed:16272756]
  4. Motohashi H, Inui K: Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the human kidney. AAPS J. 2013 Apr;15(2):581-8. doi: 10.1208/s12248-013-9465-7. Epub 2013 Feb 22. [PubMed:23435786]
  5. FDA label, metformin [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Possible transporter
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Lee N, Hebert MF, Wagner DJ, Easterling TR, Liang CJ, Rice K, Wang J: Organic Cation Transporter 3 Facilitates Fetal Exposure to Metformin during Pregnancy. Mol Pharmacol. 2018 Oct;94(4):1125-1131. doi: 10.1124/mol.118.112482. Epub 2018 Jul 16. [PubMed:30012584]
  2. Pakkir Maideen NM, Jumale A, Balasubramaniam R: Drug Interactions of Metformin Involving Drug Transporter Proteins. Adv Pharm Bull. 2017 Dec;7(4):501-505. doi: 10.15171/apb.2017.062. Epub 2017 Dec 31. [PubMed:29399540]
  3. Lee N, Duan H, Hebert MF, Liang CJ, Rice KM, Wang J: Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands. J Biol Chem. 2014 Sep 26;289(39):27055-64. doi: 10.1074/jbc.M114.570564. Epub 2014 Aug 8. [PubMed:25107910]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Pakkir Maideen NM, Jumale A, Balasubramaniam R: Drug Interactions of Metformin Involving Drug Transporter Proteins. Adv Pharm Bull. 2017 Dec;7(4):501-505. doi: 10.15171/apb.2017.062. Epub 2017 Dec 31. [PubMed:29399540]
  2. Motohashi H, Inui K: Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the human kidney. AAPS J. 2013 Apr;15(2):581-8. doi: 10.1208/s12248-013-9465-7. Epub 2013 Feb 22. [PubMed:23435786]
  3. Martinez-Guerrero LJ, Wright SH: Substrate-dependent inhibition of human MATE1 by cationic ionic liquids. J Pharmacol Exp Ther. 2013 Sep;346(3):495-503. doi: 10.1124/jpet.113.204206. Epub 2013 Jun 19. [PubMed:23785176]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Possible transporter
General Function
Nucleoside transmembrane transporter activity
Specific Function
Functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including s...
Gene Name
SLC29A4
Uniprot ID
Q7RTT9
Uniprot Name
Equilibrative nucleoside transporter 4
Molecular Weight
58058.005 Da
References
  1. Zhou M, Xia L, Wang J: Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos. 2007 Oct;35(10):1956-62. Epub 2007 Jun 28. [PubMed:17600084]
  2. Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE: Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012 Nov;22(11):820-7. doi: 10.1097/FPC.0b013e3283559b22. [PubMed:22722338]
  3. McCreight LJ, Bailey CJ, Pearson ER: Metformin and the gastrointestinal tract. Diabetologia. 2016 Mar;59(3):426-35. doi: 10.1007/s00125-015-3844-9. Epub 2016 Jan 16. [PubMed:26780750]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Possible transporter
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  2. Chowdhury S, Yung E, Pintilie M, Muaddi H, Chaib S, Yeung M, Fusciello M, Sykes J, Pitcher B, Hagenkort A, McKee T, Vellanki R, Chen E, Bristow RG, Wouters BG, Koritzinsky M: MATE2 Expression Is Associated with Cancer Cell Response to Metformin. PLoS One. 2016 Dec 13;11(12):e0165214. doi: 10.1371/journal.pone.0165214. eCollection 2016. [PubMed:27959931]
  3. Choi JH, Yee SW, Ramirez AH, Morrissey KM, Jang GH, Joski PJ, Mefford JA, Hesselson SE, Schlessinger A, Jenkins G, Castro RA, Johns SJ, Stryke D, Sali A, Ferrin TE, Witte JS, Kwok PY, Roden DM, Wilke RA, McCarty CA, Davis RL, Giacomini KM: A common 5'-UTR variant in MATE2-K is associated with poor response to metformin. Clin Pharmacol Ther. 2011 Nov;90(5):674-84. doi: 10.1038/clpt.2011.165. Epub 2011 Sep 28. [PubMed:21956618]
  4. Metformin FDA label [File]

Drug created on June 13, 2005 07:24 / Updated on October 25, 2020 09:16

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