U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C4H11N5
Molecular Weight 129.1636
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METFORMIN

SMILES

CN(C)C(=N)NC(N)=N

InChI

InChIKey=XZWYZXLIPXDOLR-UHFFFAOYSA-N
InChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)

HIDE SMILES / InChI

Molecular Formula C4H11N5
Molecular Weight 129.1636
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25333032 | http://www.rsc.org/images/eic_nov2011_metformin_tcm18-210010.pdf | https://www.ncbi.nlm.nih.gov/pubmed/22117616

Metformin is the most widely used drug to treat type 2 diabetes, and is one of only two oral antidiabetic drugs on the World Health Organization (WHO) list of essential medicines. Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. However, we still do not completely understand its mechanisms of action. The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory chain complex I. In addition, the resulting decrease in hepatic energy status activates AMPK (AMP-activated protein kinase), a cellular metabolic sensor, providing a generally accepted mechanism for the action of metformin on hepatic gluconeogenesis. The use of metformin, the most commonly prescribed drug for type 2 diabetes, was repeatedly associated with the decreased risk of the occurrence of various types of cancers, especially of pancreas and colon and hepatocellular carcinoma.

Originator

Sources: Werner E.A. and Bell J., J. Chem. Soc. Trans., 1922, 121, 1790 (DOI: 10.1039/CT9222101790)
Curator's Comment: reference retrieved from http://www.rsc.org/images/eic_nov2011_metformin_tcm18-210010.pdf

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GLUCOPHAGE

Approved Use

Metformin hydrochloride tablets, USP is indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus. Metformin hydrochloride extended-release tablets, USP is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Launch Date

7.9418878E11
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
815.39 ng/mL
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METFORMIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7694.78 ng × h/mL
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METFORMIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.19 h
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METFORMIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
Doses

Doses

DosePopulationAdverse events​
2550 mg 1 times / day steady, oral
Recommended
Dose: 2550 mg, 1 times / day
Route: oral
Route: steady
Dose: 2550 mg, 1 times / day
Sources:
unhealthy, adult
n = 141
Health Status: unhealthy
Condition: type 2 diabetes mellitus
Age Group: adult
Population Size: 141
Sources:
Disc. AE: Diarrhea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (6%)
Sources:
850 mg 1 times / day steady, oral
Recommended
Dose: 850 mg, 1 times / day
Route: oral
Route: steady
Dose: 850 mg, 1 times / day
Sources:
unhealthy, adult
Disc. AE: Lactic acidosis...
AEs leading to
discontinuation/dose reduction:
Lactic acidosis (grade 5)
Sources:
AEs

AEs

AESignificanceDosePopulation
Diarrhea 6%
Disc. AE
2550 mg 1 times / day steady, oral
Recommended
Dose: 2550 mg, 1 times / day
Route: oral
Route: steady
Dose: 2550 mg, 1 times / day
Sources:
unhealthy, adult
n = 141
Health Status: unhealthy
Condition: type 2 diabetes mellitus
Age Group: adult
Population Size: 141
Sources:
Lactic acidosis grade 5
Disc. AE
850 mg 1 times / day steady, oral
Recommended
Dose: 850 mg, 1 times / day
Route: oral
Route: steady
Dose: 850 mg, 1 times / day
Sources:
unhealthy, adult
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: Co-administration of cimetidine, pyrimethamine, trimethoprim, lansoprazole, dolutegravir and vandetanib with metformin has been shown to increase its AUC by 1.2 to 1.7-fold
Page: -
PubMed

PubMed

TitleDatePubMed
Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment.
1998 Aug
[Hepatotoxic reaction associated with metformin and chlorpropamide treatment].
1999 Feb
Association of metformin and pregnancy in the polycystic ovary syndrome. A report of three cases.
2000 Jun
[Marked creatine-phosphokinase elevation in myopathy after treatment with bezafibrate].
2000 Sep
Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study.
2000 Sep
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers.
2001
Nuclear magnetic resonance studies of hepatic glucose metabolism in humans.
2001
[Type 2 diabetes mellitus: Which place for thiazolidinediones in the therapeutic strategy?].
2001 Apr
Homocysteine and cardiovascular risk in patients with diabetes mellitus.
2001 Apr
Clinical review of glimepiride.
2001 Apr
ION-pair liquid chromatography technique for the estimation of metformin in its multicomponent dosage forms.
2001 Apr
Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance.
2001 Feb
Diabetes mellitus with left transverse sinus thrombosis and right transverse sinus aplasia.
2001 Jan
Do interventions to reduce coronary heart disease reduce the incidence of type 2 diabetes? A possible role for inflammatory factors.
2001 Jan 23
Combination therapy in type 2 diabetes: the role of repaglinide.
2001 Jan 25
Cholestatic jaundice associated with the use of metformin.
2001 Jul
Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.
2001 Jul
Digestive hemorrhage caused by a Meckel's diverticulum in a metformin-treated patient: is there any connection?
2001 Jun
Use of urea containing dialysate to avoid disequilibrium syndrome, enabling intensive dialysis treatment of a diabetic patient with renal failure and severe metformin induced lactic acidosis.
2001 Jun
[Metformin and contrast media--increased risk of lactic acidosis?].
2001 Jun 10
Rosiglitazone.
2001 Mar
Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors.
2001 Mar
The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin. A multicenter, randomized, double-blind, placebo-controlled trial.
2001 May 1
Effect of a series of novel sulphonylthioureas on glucose tolerance in the obese fa/fa Zucker rat.
2001 May-Jun
Patents

Sample Use Guides

Recommended Dosing Schedule Adults The usual starting dose of GLUCOPHAGE Tablets is 500 mg twice a day or 850 mg once a day, given with meals. In general, clinically significant responses are not seen at doses below 1500 mg per day. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. The dosage of GLUCOPHAGE must be individualized on the basis of both effectiveness and tolerability. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, GLUCOPHAGE may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given 3 times a day with meals. The usual starting dose of GLUCOPHAGE XR (metformin hydrochloride) Extended-Release Tablets is 500 mg once daily with the evening meal. In general, clinically significant responses are not seen at doses below 1500 mg per day. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. The dosage of GLUCOPHAGE XR must be individualized on the basis of both effectiveness and tolerability. If glycemic control is not achieved on GLUCOPHAGE XR 2000 mg once daily, a trial of GLUCOPHAGE XR 1000 mg twice daily should be considered. If higher doses of metformin are required, GLUCOPHAGE should be used at total daily doses up to 2550 mg administered in divided daily doses, as described above. (See CLINICAL PHARMACOLOGY: Clinical Studies.) Patients receiving GLUCOPHAGE treatment may be safely switched to GLUCOPHAGE XR once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from GLUCOPHAGE to GLUCOPHAGE XR, glycemic control should be closely monitored and dosage adjustments made accordingly (see CLINICAL PHARMACOLOGY: Clinical Studies). Pediatrics The usual starting dose of GLUCOPHAGE is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. The dosage of GLUCOPHAGE must be individualized on the basis of both effectiveness and tolerability. Safety and effectiveness of GLUCOPHAGE XR in pediatric patients have not been established.
Route of Administration: Oral
Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability.
Substance Class Chemical
Created
by admin
on Fri Dec 16 16:39:42 UTC 2022
Edited
by admin
on Fri Dec 16 16:39:42 UTC 2022
Record UNII
9100L32L2N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METFORMIN
INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
METFORMIN [VANDF]
Common Name English
METFORMIN [MI]
Common Name English
METFORMIN [USAN]
Common Name English
1,1-Dimethylbiguanide
Systematic Name English
METFORMIN EXTENDED RELEASE
Common Name English
Metformin [WHO-DD]
Common Name English
IMIDODICARBONIMIDIC DIAMIDE, N,N-DIMETHYL-
Systematic Name English
metformin [INN]
Common Name English
Classification Tree Code System Code
WHO-VATC QA10BD15
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
LIVERTOX NBK548726
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ESSENTIAL MEDICINES LIST 18.5
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD07
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD03
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD02
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD13
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BA02
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD10
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD25
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
NCI_THESAURUS C1892
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
NDF-RT N0000175565
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
EU-Orphan Drug EU/3/17/1965
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD08
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD17
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD14
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD05
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD11
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD13
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BA02
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD20
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
FDA ORPHAN DRUG 616117
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD11
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD22
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD07
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD15
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD03
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD08
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
NCI_THESAURUS C98234
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
NDF-RT N0000007698
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD02
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD14
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD10
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD16
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
FDA ORPHAN DRUG 432214
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-VATC QA10BD05
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
WHO-ATC A10BD18
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
Code System Code Type Description
DRUG CENTRAL
1725
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
PUBCHEM
4091
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
IUPHAR
4779
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
FDA UNII
9100L32L2N
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
EVMPD
SUB08831MIG
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
DRUG BANK
DB00331
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
INN
965
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
ChEMBL
CHEMBL1431
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
CAS
657-24-9
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
DAILYMED
9100L32L2N
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
MESH
D008687
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
NCI_THESAURUS
C61612
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
ECHA (EC/EINECS)
211-517-8
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
WIKIPEDIA
METFORMIN
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
MERCK INDEX
M7280
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY Merck Index
LACTMED
Metformin
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
RXCUI
6809
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY RxNorm
EPA CompTox
DTXSID2023270
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
CHEBI
6801
Created by admin on Fri Dec 16 16:39:42 UTC 2022 , Edited by admin on Fri Dec 16 16:39:42 UTC 2022
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
Km
TRANSPORTER -> SUBSTRATE
Km
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
Vmax
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
Vmax
TRANSPORTER -> INHIBITOR
EXCRETED UNCHANGED
URINE
SALT/SOLVATE -> PARENT
DERIVATIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL, PREGNANCY
PHARMACOKINETIC
ORAL, RENAL IMPAIRMENT
PHARMACOKINETIC
ORAL, GERIATRIC
PHARMACOKINETIC
ORAL, EXTENDED-RELEASE
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC GERIATRIC

MAXIMUM TOLERATED DOSE TOXICITY FORTAMET

GLUCOPHAGE XR, GLUMETZA

ORAL BIOAVAILABILITY PHARMACOKINETIC