Identification
- Summary
Metformin is a biguanide antihyperglycemic used in conjunction with diet and exercise for glycemic control in type 2 diabetes mellitus. It is also used off-label for insulin resistance in polycystic ovary syndrome (PCOS).
- Brand Names
- Actoplus Met, Avandamet, Fortamet, Glucophage, Glucovance, Glumetza, Glycon, Invokamet, Janumet, Jentadueto, Kazano, Kombiglyze, Komboglyze, Qternmet, Riomet, Segluromet, Synjardy, Trijardy, Velmetia, Xigduo
- Generic Name
- Metformin
- DrugBank Accession Number
- DB00331
- Background
Metformin is a biguanide antihyperglycemic agent and first-line pharmacotherapy used in the management of type II diabetes.23,14
Metformin is considered an antihyperglycemic drug because it lowers blood glucose concentrations in type II diabetes without causing hypoglycemia. It 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, making it an effective choice for obese patients type II diabetes.12
Metformin was first approved in Canada in 1972,8 and received subsequent FDA approval in the US in 1995.23
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Metformin (DB00331)
- 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 immediate-release formulations
Metformin is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10 years old with type 2 diabetes mellitus.24
Metformin extended-release tablet (XR)
The extended-release formulation of metformin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Safety in children has not been determined to this date.23
Metformin combination products
Metformin is a component of a variety of combination products with other anti-diabetic agents. It is indicated, along with diet and exercise, to improve glycemic control in adult patients with type 2 diabetes mellitus in combination with DPP-4 inhibitors (sitagliptin, linagliptin, alogliptin, or saxagliptin),22,27,28,29,30 in combination with SGLT2 inhibitors (canagliflozin, empagliflozin, ertugliflozin, or dapagliflozin),22,26,31,32,33 or in combination with pioglitazone.25
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to prevent Cardiovascular mortality Combination Product in combination with: Dapagliflozin (DB06292) •••••••••••• ••••• ••••••• •••••• ••••••• •••••• •••• •••• ••• ••••••••••• •• •••••• ••••••• ••••••• •••••••• ••••••• Used as adjunct in combination to prevent Cardiovascular mortality Combination Product in combination with: Dapagliflozin (DB06292) •••••••••••• ••••• •••• • •••••••• ••••••••• •••••••• •••••••• ••••••••• ••••••• •••••••• ••••••• Used as adjunct in combination to prevent End stage renal disease (esrd) Combination Product in combination with: Dapagliflozin (DB06292) •••••••••••• ••••• ••••••• •••••• ••••••• •••••• •••• •••• ••• ••••••••••• •• •••••• ••••••• ••••••• •••••••• ••••••• Used as adjunct in combination to prevent Hospitalizations Combination Product in combination with: Dapagliflozin (DB06292) •••••••••••• ••••• ••••••• •••••• ••••••• •••••• •••• •••• ••• ••••••••••• •• •••••• •••••••• •••• • •••••••• •••••••• ••••••• •••••••• ••••••• Used as adjunct in combination to prevent Hospitalizations Combination Product in combination with: Dapagliflozin (DB06292) •••••••••••• ••••• •••• • •••••••• ••••••••• •••••••• •••••••• ••••••••• ••••••• •••••••• ••••••• - Contraindications & Blackbox Warnings
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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 elevations in blood glucose when the pancreas can no longer compensate. In patients diagnosed with type 2 diabetes, insulin is unable to exert adequate effects on tissues and cells (i.e. insulin resistance)19 and insulin deficiency may also be present.21
Metformin reduces 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.23
Effect on fasting plasma glucose (FPG) and Glycosylated hemoglobin (HbA1c)
HbA1c is an important periodic measure of glycemic control 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.23 Glycosylated hemoglobin (HbA1c) was decreased by about 1.4% in subjects receiving metformin, and increased by 0.4% in subjects receiving placebo only.23
- 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 (also called gluconeogenesis), decreasing the intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilization.23 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
Target Actions Organism AElectron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial inhibitorHumans A5'-AMP-activated protein kinase subunit beta-1 induceractivatorHumans UGlycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic inhibitorHumans - 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.24
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.24
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.23
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.24
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.23
- 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.24
- Protein binding
Metformin is negligibly bound to plasma proteins.24
- 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.24
- Route of elimination
This drug is substantially excreted by the kidney.24
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.24
- Half-life
The plasma elimination half-life of metformin is 6.2 hours in the plasma.24 The elimination half-life in the blood is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.24
- 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.24
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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.34
A note on lactic acidosis
Metformin decreases liver uptake of lactate, thereby increasing lactate blood levels which may increase the risk of lactic acidosis.24 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.24 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/mL.24
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.24
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.24
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.24 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.24
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.24
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.24
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Metformin may decrease the excretion rate of Abacavir which could result in a higher serum level. Abemaciclib The excretion of Abemaciclib can be decreased when combined with Metformin. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Metformin. Acebutolol The therapeutic efficacy of Metformin can be increased when used in combination with Acebutolol. Aceclofenac Aceclofenac may decrease the excretion rate of Metformin which could result in a higher serum level. - Food Interactions
- Avoid alcohol.
- Take with food. Food reduces irritation.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Metformin hydrochloride 786Z46389E 1115-70-4 OETHQSJEHLVLGH-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
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Acc-metformin Tablet 850 mg Oral Accel Pharma Inc Not applicable Not applicable Canada 
Bci Metformin Tablet 500 mg Oral Baker Cummins Inc 2005-04-07 2006-10-03 Canada Bci Metformin Tablet 850 mg Oral Baker Cummins Inc 2005-07-04 2006-10-03 Canada Fortamet Tablet, film coated, extended release 1000 mg/1 Oral SHIONOGI INC. 2004-04-27 Not applicable US 
Fortamet Tablet, extended release 1000 mg/1 Oral Physicians Total Care, Inc. 2010-02-18 Not applicable US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-metformin Tablet 500 mg Oral Accord Healthcare Inc Not applicable Not applicable Canada Ach-metformin Tablet 850 mg Oral Accord Healthcare Inc Not applicable Not applicable Canada Ag-metformin Tablet 500 mg Oral Angita Pharma Inc. 2023-01-04 Not applicable Canada Ag-metformin Tablet 850 mg Oral Angita Pharma Inc. 2023-01-04 Not applicable Canada Apo-metformin Tablet 500 mg Oral Apotex Corporation 1995-12-31 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ACORT 15/850 MG FILM TABLET, 30 ADET Metformin hydrochloride (850 mg) + Pioglitazone hydrochloride (15 mg) Tablet, film coated Oral TRIPHARMA İLAÇ SAN. VE TİC. A.Ş. 2011-10-31 Not applicable Turkey 
ACORT 15/850 MG FILM TABLET, 60 ADET Metformin hydrochloride (850 mg) + Pioglitazone hydrochloride (15 mg) Tablet, film coated Oral TRIPHARMA İLAÇ SAN. VE TİC. A.Ş. 2020-08-14 Not applicable Turkey ACORT 15/850 MG FILM TABLET, 90 ADET Metformin hydrochloride (850 mg) + Pioglitazone hydrochloride (15 mg) Tablet, film coated Oral TRIPHARMA İLAÇ SAN. VE TİC. A.Ş. 2011-10-31 Not applicable Turkey ACPIMET Metformin hydrochloride (850 MG) + Pioglitazone (15 MG) Tablet, film coated Oral บริษัท โนวาร์ตีส (ประเทศไทย) จำกัด 2017-02-14 2020-09-17 Thailand 
Actoplus Met Metformin hydrochloride (500 mg/1) + Pioglitazone hydrochloride (15 mg/1) Tablet, film coated Oral Physicians Total Care, Inc. 2006-01-04 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Appformin Metformin hydrochloride (500 mg/1) + Tyrosine (100 mg/1) Kit Oral Physician Therapeutics Llc 2011-02-07 Not applicable US Appformin-D Metformin hydrochloride (500 mg/1) + Tyrosine (100 mg/1) Kit Oral Physician Therapeutics Llc 2011-07-07 Not applicable US PIO-MET 15/500 MG FILM TABLET, 30 ADET Metformin (500 mg) + Pioglitazone (15 mg) Tablet, coated Oral TAKEDA İLAÇ SAĞLIK SAN. TİC. LTD. ŞTİ. 2019-04-30 Not applicable Turkey
Categories
- ATC Codes
- A10BD23 — Metformin and ertugliflozin
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BA — Biguanides
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- 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)
- Affected organisms
- Humans and other mammals
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
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- 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. [Article]
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- 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. [Article]
- 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. [Article]
- Lucis OJ: The status of metformin in Canada. Can Med Assoc J. 1983 Jan 1;128(1):24-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Misra P, Chakrabarti R: The role of AMP kinase in diabetes. Indian J Med Res. 2007 Mar;125(3):389-98. [Article]
- 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. [Article]
- 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. [Article]
- 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).
- Institute for Quality and Efficiency in Health Care (IQWiG) (2008). Type 2 diabetes: Overview. InformedHealth.org.
- Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program [Link]
- UptoDate: Pathogenesis of type 2 diabetes mellitus [Link]
- FDA Approved Drug Products: Trijardy XR (empagliflozin/linagliptin/metformin) extended-release tablets [Link]
- FDA Approved Drug Products: Glumetza (metformin hydrochloride) extended-release tablets for oral use [Link]
- FDA Approved Drug Products: Riomet (metformin hydrochloride) oral solution [Link]
- FDA Approved Drug Products: Actoplus Met (pioglitazone/metformin) oral tablets [Link]
- FDA Approved Products: INVOKAMET (canagliflozin and metformin hydrochloride tablets), for oral use [Link]
- FDA Approved Drug Products: Janumet (sitagliptin and metformin hydrochloride) tablets for oral use [Link]
- FDA Approved Drug Products: Jentadueto (linagliptin and metformin hydrochloride) tablets for oral use [Link]
- FDA Approved Drug Products: Kazano (alogliptin and metformin hydrochloride) tablets for oral use [Link]
- FDA Approved Drug Products: Kombiglyze XR (saxagliptin and metformin hydrochloride) extended-release tablets for oral use [Link]
- FDA Approved Drug Products: Segluromet (ertugliflozin and metformin hydrochloride) tablets for oral use [Link]
- FDA Approved Drug Products: Synjardy (empagliflozin/metformin) oral tablets [Link]
- FDA Approved Drug Products: Xigduo XR (metformin hydrochloride/dapagliflozin) extended-release tablets for oral use [Link]
- CaymanChem: Metformin hydrochloride Safety Data Sheet [Link]
- DailyMed Label: GLUCOPHAGE (metformin hydrochloride) tablets, for oral use [Link]
- Comparing Dissolution Profiles of of Seven Metformin Formulations in Simulated Intestinal Fluid [File]
- Glumetza FDA [File]
- Metformin label [File]
- Metformin Canadian monograph [File]
- MedSafe NZ Metformin mylan [File]
- External Links
- Human Metabolome Database
- HMDB0001921
- KEGG Drug
- D04966
- KEGG Compound
- C07151
- PubChem Compound
- 4091
- PubChem Substance
- 46507752
- ChemSpider
- 3949
- BindingDB
- 50229665
- 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
- PDB Entries
- 5g5j / 8sc4
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Atrial Fibrillation 1 4 Active Not Recruiting Treatment Cardiac Fibrosis / Plasminogen Activator Inhibitor-1 Deficiency 1 4 Active Not Recruiting Treatment Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD / Polycystic Ovarian Syndrome (PCOS) / Syndrome, Metabolic 1 4 Active Not Recruiting Treatment Impaired Fasting Glucose (IFG) / Impaired Glucose Tolerance 1 4 Active Not Recruiting Treatment Polycystic Ovarian Syndrome (PCOS) 1
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
Form Route Strength Tablet, film coated, extended release Oral 1000 mg Tablet, film coated, extended release Oral 500 mg Tablet, film coated, extended release Oral 750 mg Tablet, extended release Oral 850 mg Tablet Oral 500.000 mg Tablet Oral 882.350 mg Kit Oral Tablet Oral 526.316 mg Powder Not applicable 95 mg/100mg Drug delivery system Oral 500.000 mg Tablet Oral 750.000 mg Tablet, film coated Oral 850.00 MG Tablet, film coated Oral 500.00 mg Tablet, film coated, extended release Oral Tablet Oral 750 mg Tablet, film coated Oral Tablet, extended release Oral 850 g Tablet Oral 95 % Tablet Oral 850.000 mg Kit Oral 500 mg/1 Tablet, extended release Oral Solution Oral 0.40 g Tablet Oral 5.00 mg Solution Oral 10 g Tablet, coated Oral 1000 mg Tablet, delayed release Oral Tablet Oral Tablet, coated Oral Tablet Oral 500 mg Powder, for solution Oral 1000 MG Powder, for solution Oral 500 MG Powder, for solution Oral 850 MG Tablet Oral 1000 mg Tablet, extended release Oral 500 mg Tablet, film coated Oral 5 mg Tablet, film coated, extended release Oral 1000 mg/1 Tablet, film coated, extended release Oral 500 mg/1 Tablet Oral 500.00 mg Powder, for solution Oral Tablet Oral 850.00 mg Tablet Oral 526.310 mg Tablet, film coated, extended release Oral 1000 mg Tablet, film coated, extended release Oral 500 mg Tablet, film coated Oral 1000.0 mg Tablet, film coated Oral 500.0 mg Tablet, film coated Oral 850.0 mg Tablet, film coated, extended release Oral Tablet, delayed release Oral 500 mg Tablet, film coated Oral Tablet, coated Oral Powder 97 mg/100mg Powder Not applicable 500 mg/1kg Tablet Oral Tablet; tablet, film coated Oral 850 mg Powder Not applicable 1 kg/1kg Tablet Not applicable 1000 mg/1 Tablet Not applicable 500 mg/1 Tablet Not applicable 850 mg/1 Tablet Oral 1000 mg/1 Tablet Oral 500 mg/1 Tablet Oral 625 mg/1 Tablet Oral 850 mg/1 Tablet, coated Oral 1000 mg/1 Tablet, coated Oral 500 mg/1 Tablet, coated Oral 850 mg/1 Tablet, extended release Oral 1000 mg/1 Tablet, extended release Oral 500 mg/1 Tablet, extended release Oral 750 mg/1 Tablet, extended release Oral 850 mg/1 Tablet, film coated Oral 1000 mg/1 Tablet, film coated Oral 500 mg/1 Tablet, film coated Oral 850 mg/1 Tablet Oral 750 mg/1 Tablet, film coated Oral 1.000 MG Tablet, film coated Oral 250 mg Tablet Oral 250 mg Powder Not applicable 750 mg/1kg Tablet, film coated Oral 390 MG Tablet, film coated Oral 663 MG Tablet, for suspension Tablet, effervescent 1000 mg Tablet, effervescent 500 mg Tablet, effervescent 850 mg Tablet, delayed release Oral Tablet Oral 56.690 mg Tablet, film coated Oral 12.5 mg Tablet, film coated Oral 15 MG Solution Oral 10.000 g Tablet, extended release Oral 50000000 mg Tablet Oral 1000.000 mg Tablet, effervescent Oral Tablet Oral 500 mg / tab Solution Oral 500 mg/5mL For suspension, extended release Oral 500 mg/5mL Tablet Oral 850.000 mg Tablet, film coated Tablet, film coated Oral 50 mg/1000mg Tablet, film coated Oral 50 mg/850mg Tablet, extended release Oral Tablet, film coated Oral 150.00 mg Tablet, film coated Oral 50.00 mg Tablet, film coated, extended release Oral 10 mg Tablet, film coated, extended release Oral 5 mg Tablet, extended release Oral 1005.04 mg Tablet Oral 894.737 mg Tablet Oral 850 mg Tablet, film coated Oral 1000 mg Tablet, extended release Oral 1000 mg Tablet, extended release Oral 750 mg Tablet, film coated Oral 850 mg Tablet, film coated Oral 500 mg Tablet, coated Oral 500 mg Tablet, coated Oral 850 mg - Prices
Unit description Cost Unit Fortamet er 1000 mg tablet 6.93USD tablet Fortamet 1000 mg 24 Hour tablet 6.01USD tablet Fortamet 500 mg 24 Hour tablet 2.55USD tablet Fortamet er 500 mg tablet 2.48USD tablet Glucophage 1000 mg tablet 2.33USD tablet Metformin hcl crystals 2.14USD g Glucophage 850 mg tablet 1.94USD tablet Glucophage XR 750 mg 24 Hour tablet 1.8USD tablet Glucophage xr 750 mg tablet 1.71USD tablet Metformin hcl 1000 mg tablet 1.48USD tablet MetFORMIN HCl 750 mg 24 Hour tablet 1.25USD tablet Metformin hcl 850 mg tablet 1.22USD tablet Glucophage XR 500 mg 24 Hour tablet 1.17USD tablet Glucophage 500 mg tablet 1.14USD tablet Glucophage xr 500 mg tablet 1.14USD tablet Glucophage xr 500 mg tablet sa 1.11USD tablet MetFORMIN HCl 500 mg 24 Hour tablet 0.75USD tablet Metformin hcl 500 mg tablet 0.72USD tablet Glucophage 850 mg Tablet 0.38USD tablet Glucophage 500 mg Tablet 0.3USD tablet Riomet 500 mg/5 ml solution 0.27USD ml Riomet 500 mg/5ml Solution 0.27USD ml Apo-Metformin 850 mg Tablet 0.21USD tablet Co Metformin 850 mg Tablet 0.21USD tablet Mylan-Metformin 850 mg Tablet 0.21USD tablet Novo-Metformin 850 mg Tablet 0.21USD tablet Nu-Metformin 850 mg Tablet 0.21USD tablet Pms-Metformin 850 mg Tablet 0.21USD tablet Ratio-Metformin Hydrochloride 850 mg Tablet 0.21USD tablet Sandoz Metformin Fc 850 mg Tablet 0.21USD tablet Pms-Metformin 500 mg Tablet 0.13USD tablet Ran-Metformin 500 mg Tablet 0.13USD tablet Ratio-Metformin Hydrochloride 500 mg Tablet 0.13USD tablet Sandoz Metformin Fc 500 mg Tablet 0.13USD tablet Zym-Metformin 500 mg Tablet 0.13USD tablet Apo-Metformin 500 mg Tablet 0.13USD tablet Co Metformin 500 mg Tablet 0.13USD tablet Mylan-Metformin 500 mg Tablet 0.13USD tablet Novo-Metformin 500 mg Tablet 0.13USD tablet Nu-Metformin 500 mg Tablet 0.13USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2476496 No 2009-12-15 2023-02-21 Canada CA2412671 No 2006-10-03 2021-02-26 Canada US7326708 Yes 2008-02-05 2027-05-24 US US7407955 Yes 2008-08-05 2025-11-02 US US6150383 No 2000-11-21 2016-06-19 US US6211205 No 2001-04-03 2016-06-19 US US6303640 No 2001-10-16 2016-08-09 US US6329404 No 2001-12-11 2016-06-19 US US6699871 Yes 2004-03-02 2023-01-26 US US7125873 Yes 2006-10-24 2023-01-26 US US5965584 No 1999-10-12 2016-06-19 US US6166042 No 2000-12-26 2016-06-19 US US6166043 No 2000-12-26 2016-06-19 US US6172090 No 2001-01-09 2016-06-19 US US6790459 No 2004-09-14 2021-03-17 US US7919116 No 2011-04-05 2018-03-20 US US8475841 No 2013-07-02 2018-03-20 US US6099859 No 2000-08-08 2018-03-20 US US6866866 No 2005-03-15 2021-03-17 US US7785627 No 2010-08-31 2026-07-31 US US7959946 No 2011-06-14 2026-07-31 US US8470368 No 2013-06-25 2023-09-19 US US8668931 No 2014-03-11 2023-09-19 US US9060941 No 2015-06-23 2023-09-19 US US6495162 No 2002-12-17 2018-03-20 US US8414921 Yes 2013-04-09 2029-01-21 US US6288095 Yes 2001-09-11 2017-08-11 US US7358366 Yes 2008-04-15 2020-10-19 US US6150384 No 2000-11-21 2016-06-19 US US6303146 Yes 2001-10-16 2020-01-14 US US6660300 No 2003-12-09 2018-03-19 US US6475521 No 2002-11-05 2018-03-19 US US8236345 No 2012-08-07 2022-10-07 US US6890957 No 2005-05-10 2023-09-14 US US6340475 No 2002-01-22 2016-09-19 US US6635280 No 2003-10-21 2016-09-19 US US6488962 No 2002-12-03 2020-06-20 US US7780987 No 2010-08-24 2025-03-23 US US8323692 No 2012-12-04 2025-03-23 US US6723340 No 2004-04-20 2021-10-25 US US9101660 No 2015-08-11 2027-01-22 US US6303661 No 2001-10-16 2017-04-24 US US6890898 No 2005-05-10 2019-02-02 US US7078381 No 2006-07-18 2019-02-02 US US7459428 No 2008-12-02 2019-02-02 US US7807689 No 2010-10-05 2028-06-27 US US8173663 No 2012-05-08 2025-03-15 US US8288539 No 2012-10-16 2025-03-15 US USRE44186 No 2013-04-30 2023-07-31 US US8119648 No 2012-02-21 2023-08-12 US US8178541 No 2012-05-15 2023-08-12 US US8846695 Yes 2014-09-30 2030-12-04 US US9173859 Yes 2015-11-03 2027-11-04 US US8673927 Yes 2014-03-18 2027-11-04 US US8883805 Yes 2014-11-11 2026-05-26 US US9155705 Yes 2015-10-13 2030-11-21 US US8628799 No 2014-01-14 2025-07-13 US US8900638 No 2014-12-02 2029-05-24 US US8222219 No 2012-07-17 2024-07-30 US US8513202 No 2013-08-20 2027-12-03 US US7943582 No 2011-05-17 2029-02-26 US US8785403 No 2014-07-22 2024-07-30 US US7943788 No 2011-05-17 2027-07-14 US US8685934 No 2014-04-01 2030-05-26 US US8501698 Yes 2013-08-06 2027-12-20 US US6414126 No 2002-07-02 2020-10-04 US US6515117 Yes 2003-02-04 2026-04-04 US US6936590 No 2005-08-30 2020-10-04 US US9198925 No 2015-12-01 2020-10-04 US US7919598 No 2011-04-05 2029-12-16 US US8716251 No 2014-05-06 2028-03-21 US US8551957 Yes 2013-10-08 2030-04-14 US US7713938 Yes 2010-05-11 2027-10-15 US US7579449 Yes 2009-08-25 2029-02-01 US US9320714 No 2016-04-26 2029-02-03 US US9415016 Yes 2016-08-16 2029-10-02 US US9339472 No 2016-05-17 2025-07-13 US US9555001 Yes 2017-01-31 2033-09-06 US US9616028 No 2017-04-11 2030-11-12 US US8080580 No 2011-12-20 2030-07-13 US US9439902 No 2016-09-13 2030-10-21 US US9308204 No 2016-04-12 2030-10-21 US US9949998 Yes 2018-04-24 2034-12-11 US US9949997 Yes 2018-04-24 2034-11-17 US US10022379 Yes 2018-07-17 2029-10-02 US US10258637 Yes 2019-04-16 2034-10-03 US US10406172 No 2019-09-10 2030-06-15 US US9962336 No 2018-05-08 2035-05-01 US US10596120 Yes 2020-03-24 2032-09-07 US US10610489 Yes 2020-04-07 2031-03-30 US US10973827 Yes 2021-04-13 2029-10-02 US US11090323 Yes 2021-08-17 2034-10-03 US US11564886 No 2012-03-07 2032-03-07 US US11576894 No 2010-07-06 2030-07-06 US US11833166 No 2014-04-03 2034-04-03 US US11813275 No 2014-04-03 2034-04-03 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 223-226 °C http://www.molbase.com/en/properties_1115-70-4-moldata-22670.html boiling point (°C) 224.1ºC at 760 mmHg http://www.molbase.com/en/properties_1115-70-4-moldata-22670.html water solubility Freely soluble https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021748s025lbl.pdf logP -2.6 https://www.sciencedirect.com/science/article/pii/S1319016413001229 pKa 12.4 https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021748s025lbl.pdf - Predicted Properties
Property Value Source Water Solubility 1.38 mg/mL ALOGPS logP -1.8 ALOGPS logP -0.92 Chemaxon logS -2 ALOGPS pKa (Strongest Basic) 12.33 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 88.99 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 56.64 m3·mol-1 Chemaxon Polarizability 13.43 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9156 Blood Brain Barrier + 0.5868 Caco-2 permeable - 0.8958 P-glycoprotein substrate Non-substrate 0.6643 P-glycoprotein inhibitor I Non-inhibitor 0.9613 P-glycoprotein inhibitor II Non-inhibitor 0.8892 Renal organic cation transporter Non-inhibitor 0.7518 CYP450 2C9 substrate Non-substrate 0.7929 CYP450 2D6 substrate Non-substrate 0.7325 CYP450 3A4 substrate Non-substrate 0.6906 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9159 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.913 CYP450 3A4 inhibitor Non-inhibitor 0.9506 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9763 Ames test Non AMES toxic 0.7367 Carcinogenicity Non-carcinogens 0.6691 Biodegradation Not ready biodegradable 0.938 Rat acute toxicity 1.7407 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9807 hERG inhibition (predictor II) Non-inhibitor 0.9274
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 125.859838 predictedDarkChem Lite v0.1.0 [M-H]- 125.844538 predictedDarkChem Lite v0.1.0 [M-H]- 125.727138 predictedDarkChem Lite v0.1.0 [M-H]- 125.798738 predictedDarkChem Lite v0.1.0 [M-H]- 130.61507 predictedDeepCCS 1.0 (2019) [M+H]+ 126.768138 predictedDarkChem Lite v0.1.0 [M+H]+ 126.548838 predictedDarkChem Lite v0.1.0 [M+H]+ 126.581538 predictedDarkChem Lite v0.1.0 [M+H]+ 126.759738 predictedDarkChem Lite v0.1.0 [M+H]+ 132.9076 predictedDeepCCS 1.0 (2019) [M+Na]+ 125.625738 predictedDarkChem Lite v0.1.0 [M+Na]+ 125.933838 predictedDarkChem Lite v0.1.0 [M+Na]+ 125.979638 predictedDarkChem Lite v0.1.0 [M+Na]+ 126.171238 predictedDarkChem Lite v0.1.0 [M+Na]+ 141.76653 predictedDeepCCS 1.0 (2019)
Targets
- 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
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InducerActivator
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007 Feb 16;100(3):328-41. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
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
- 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. [Article]
- 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. [Article]
- Zolk O: Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther. 2009 Dec;86(6):595-8. doi: 10.1038/clpt.2009.144. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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. [Article]
- Zolk O: Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther. 2009 Dec;86(6):595-8. doi: 10.1038/clpt.2009.144. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Metformin FDA label [File]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55