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

Details

Stereochemistry ACHIRAL
Molecular Formula C4H11N5.ClH
Molecular Weight 165.625
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METFORMIN HYDROCHLORIDE

SMILES

Cl.CN(C)C(=N)NC(N)=N

InChI

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

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

Molecular Formula ClH
Molecular Weight 36.461
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

1995
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
The short-term effect of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus.
2000 Nov-Dec
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers.
2001
Pathogenesis of type 2 diabetes mellitus.
2001
Nuclear magnetic resonance studies of hepatic glucose metabolism in humans.
2001
[Insulin sensitivity and polycystic ovarian syndrome].
2001 Apr
Homocysteine and cardiovascular risk in patients with diabetes mellitus.
2001 Apr
The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.
2001 Apr
Sulfonylurea treatment of type 2 diabetic patients does not reduce the vasodilator response to ischemia.
2001 Apr
Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes.
2001 Apr
ION-pair liquid chromatography technique for the estimation of metformin in its multicomponent dosage forms.
2001 Apr
Metformin-associated lactic acidosis.
2001 Apr
Prevention of pancreatic cancer induction in hamsters by metformin.
2001 Apr
[Metformin and intravascular contrast media. National guidelines 2001-03-16].
2001 Apr 18
Nateglinide for type 2 diabetes.
2001 Apr 2
Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin.
2001 Aug
Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes.
2001 Aug 15
Management of diabetes mellitus in three settings in Jamaica.
2001 Feb
Lactic acidosis update for critical care clinicians.
2001 Feb
Metformin retention independent of renal failure in intestinal occlusion.
2001 Feb
[Type 2 diabetes: what therapeutic strategy?].
2001 Feb 17
Diabetes in elderly adults.
2001 Jan
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
Relationship between ethnicity and glycemic control, lipid profiles, and blood pressure during the first 9 years of type 2 diabetes: U.K. Prospective Diabetes Study (UKPDS 55).
2001 Jul
Nateglinide.
2001 Jul 1
Digestive hemorrhage caused by a Meckel's diverticulum in a metformin-treated patient: is there any connection?
2001 Jun
Thiazolidinediones and liver toxicity.
2001 Jun
The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome.
2001 Jun
The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes.
2001 Jun
[Metformin and contrast media--increased risk of lactic acidosis?].
2001 Jun 10
Metformin and intervention in polycystic ovary syndrome. Endocrine Society of Australia, the Australian Diabetes Society and the Australian Paediatric Endocrine Group.
2001 Jun 4
Comparison of the metabolic effects of metformin and troglitazone on fructose-induced insulin resistance in male Sprague-Dawley rats.
2001 Mar
Rosiglitazone.
2001 Mar
Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51).
2001 Mar
Insulin-lowering drugs in polycystic ovary syndrome.
2001 Mar
[Role and modalities of insulin treatment in type 2 diabetics].
2001 Mar
Improved glycaemic control with miglitol in inadequately-controlled type 2 diabetics.
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
Metformin and the polycystic ovary syndrome.
2001 Mar
Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.
2001 Mar
Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study.
2001 Mar
Preparation and characterisation of rose Bengal-loaded surface-modified albumin nanoparticles.
2001 Mar 12
Preclinical evaluation of pharmacokinetic-pharmacodynamic rationale for oral CR metformin formulation.
2001 Mar 12
Direct-to-consumer advertisements for Glucophage XR.
2001 Mar 19
The oral insulin sensitizer, thiazolidinedione, increases plasma vascular endothelial growth factor in type 2 diabetic patients.
2001 May
Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin resistance.
2001 May
[Insulin therapy in the type 2 obese diabetic patient. Supplementing the deficit].
2001 May 24
[Metformin in the treatment of type 1 diabetics--a placebo controlled study].
2001 May 24
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 15 15:46:19 GMT 2023
Edited
by admin
on Fri Dec 15 15:46:19 GMT 2023
Record UNII
786Z46389E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METFORMIN HYDROCHLORIDE
EMA EPAR   EP   HSDB   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
METFORMIN HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
DIABEFAGOS
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF SEGLUROMET
Brand Name English
EX404
Code English
KAZANO COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
METFORMIN HCL
Common Name English
JANUMET COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF KOMBIGLYZE XR
Common Name English
RIOMET ER
Brand Name English
GLUCAMINOL
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF QTERNMET
Brand Name English
FORTAMET
Brand Name English
RIOMET
Brand Name English
SIAMFORMET
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF GLUCOVANCE
Common Name English
METFORMIN HYDROCHLORIDE COMPONENT OF METAGLIP
Brand Name English
XIGDUO COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
METFORMIN HYDROCHLORIDE [MI]
Common Name English
METFORMIN HYDROCHLORIDE [MART.]
Common Name English
GLUCOPHAGE
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF JENTADUETO
Common Name English
METFORMIN HYDROCHLORIDE [EMA EPAR]
Common Name English
DIABEX
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF JANUMET
Brand Name English
INVOKAMET COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
EX-404
Code English
GLUCOVANCE COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
ZITUVIMET COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
METAGLIP COMPONENT METFORMIN HYDROCHLORIDE
Common Name English
METFORMIN HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
METFORMIN HYDROCHLORIDE [USP-RS]
Common Name English
METFORMIN HYDROCHLORIDE COMPONENT OF SYNJARDY
Brand Name English
NEODIPA
Brand Name English
ACTOPLUS MET COMPONENT METFORMIN HYDROCHLORIDE
Common Name English
LA-6023
Code English
1,1-Dimethylbiguanide monohydrochloride
Systematic Name English
METFORMIN HYDROCHLORIDE [USAN]
Common Name English
METFORMIN HYDROCHLORIDE COMPONENT OF INVOKAMET
Brand Name English
QTERNMET COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
METFORMIN HYDROCHLORIDE [VANDF]
Common Name English
IMIDODICARBONIMIDIC DIAMIDE, N,N-DIMETHYL-, MONOHYDROCHLORIDE
Common Name English
TRIJARDY XR COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
Metformin hydrochloride [WHO-DD]
Common Name English
METFORMIN HYDROCHLORIDE COMPONENT OF TRIJARDY XR
Brand Name English
METFORMIN HYDROCHLORIDE [ORANGE BOOK]
Common Name English
METFORMIN HYDROCHLORIDE COMPONENT OF ACTOPLUS MET
Common Name English
NSC-91485
Code English
METFORMIN HYDROCHLORIDE COMPONENT OF KAZANO
Brand Name English
GLUCOPHAGE XR
Brand Name English
JENTADUETO COMPONENT OF METFORMIN HYDROCHLORIDE
Common Name English
GLUMETZA
Brand Name English
KOMBIGLYZE XR COMPONENT METFORMIN HYDROCHLORIDE
Common Name English
APOPHAGE
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF QTERNMET XR
Brand Name English
SEGLUROMET COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
BENOFOMIN
Brand Name English
METFORMIN HYDROCHLORIDE [JAN]
Common Name English
METFORMIN HYDROCHLORIDE [HSDB]
Common Name English
WALAPHAGE
Brand Name English
METFORMIN HYDROCHLORIDE COMPONENT OF XIGDUO
Brand Name English
QTERNMET XR COMPONENT METFORMIN HYDROCHLORIDE
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C98234
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
NCI_THESAURUS C1892
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C29251
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
FDA UNII
786Z46389E
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
NSC
91485
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
ECHA (EC/EINECS)
214-230-6
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
SMS_ID
100000091366
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
DRUG BANK
DBSALT000114
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
HSDB
7080
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
PUBCHEM
14219
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
RS_ITEM_NUM
1396309
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
ChEMBL
CHEMBL1431
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
EPA CompTox
DTXSID9037246
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
USAN
HH-51
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
DAILYMED
786Z46389E
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
CHEBI
6802
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
CHEBI
6801
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
RXCUI
235743
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY RxNorm
EVMPD
SUB03200MIG
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
CAS
1115-70-4
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY
MERCK INDEX
m7280
Created by admin on Fri Dec 15 15:46:19 GMT 2023 , Edited by admin on Fri Dec 15 15:46:19 GMT 2023
PRIMARY Merck Index
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