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

Details

Stereochemistry ACHIRAL
Molecular Formula C4H11N5
Molecular Weight 129.1638
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

Description
Curator's Comment:: 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 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

794188800000
Primary
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
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
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
Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance.
2001
Pathogenesis of type 2 diabetes mellitus.
2001
[Type 2 diabetes mellitus: Which place for thiazolidinediones in the therapeutic strategy?].
2001 Apr
[Thiazolidinediones: clinical data and perspectives].
2001 Apr
[Insulin sensitivity and polycystic ovarian syndrome].
2001 Apr
Homocysteine and cardiovascular risk in patients with diabetes mellitus.
2001 Apr
Acute postoperative metabolic complications of diabetes.
2001 Apr
Sulfonylurea treatment of type 2 diabetic patients does not reduce the vasodilator response to ischemia.
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
Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin.
2001 Aug
[Effects of metformin on insulin resistance and on ovarian steroidogenesis in women with polycystic ovary syndrome].
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
Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up.
2001 Feb
[Type 2 diabetes: what therapeutic strategy?].
2001 Feb 17
Cholestatic jaundice associated with the use of metformin.
2001 Jul
Case of the month. Hepatic and renal failure in a patient taking troglitazone and 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
Re: Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention.
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
Management of type 2 diabetes. Evolving strategies for treatment.
2001 Jun
Lactic acidosis in metformin therapy: searching for a link with metformin in reports of 'metformin-associated lactic acidosis'.
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
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
Safety and efficacy of acarbose in the treatment of Type 2 diabetes: data from a 5-year surveillance study.
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
Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51).
2001 Mar
Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes.
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 and the polycystic ovary syndrome.
2001 Mar
Preparation and characterisation of rose Bengal-loaded surface-modified albumin nanoparticles.
2001 Mar 12
[Current and future aspects of oral antidiabetic agents in type 2 diabetes].
2001 May
The oral insulin sensitizer, thiazolidinedione, increases plasma vascular endothelial growth factor in type 2 diabetic patients.
2001 May
Use of the ligand immunofunctional assay for human insulin-like growth factor ((IGF) binding protein-3 (IGFBP-3) to analyze IGFBP-3 proteolysis and igf-i bioavailability in healthy adults, GH-deficient and acromegalic patients, and diabetics.
2001 May
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
[Metformin and anesthesia--how great is the risk of lactic acidosis].
2001 May 18
[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
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.
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 [WHO-DD]
Common Name English
METFORMIN EXTENDED RELEASE
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 Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
LIVERTOX 610
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 18.5
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-VATC QA10BD07
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-VATC QA10BD03
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BD02
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-VATC QA10BD13
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BA02
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD10
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD25
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
NCI_THESAURUS C1892
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
NDF-RT N0000175565
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
EU-Orphan Drug EU/3/17/1965
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-VATC QA10BD08
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BD17
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD14
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD05
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-VATC QA10BD11
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BD13
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-VATC QA10BA02
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BD20
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
FDA ORPHAN DRUG 616117
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD11
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD22
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD07
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD15
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD03
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-ATC A10BD08
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
NCI_THESAURUS C98234
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
NDF-RT N0000007698
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-VATC QA10BD02
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-VATC QA10BD14
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-VATC QA10BD10
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BD16
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
FDA ORPHAN DRUG 432214
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
WHO-VATC QA10BD05
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
WHO-ATC A10BD18
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
Code System Code Type Description
DRUG CENTRAL
1725
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
PUBCHEM
4091
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
PRIMARY
IUPHAR
4779
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
FDA UNII
9100L32L2N
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
EVMPD
SUB08831MIG
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
DRUG BANK
DB00331
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
INN
965
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL1431
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
CAS
657-24-9
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
MESH
D008687
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
NCI_THESAURUS
C61612
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
ECHA (EC/EINECS)
211-517-8
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
WIKIPEDIA
METFORMIN
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
PRIMARY
MERCK INDEX
M7280
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY Merck Index
LACTMED
Metformin
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY
RXCUI
6809
Created by admin on Fri Jun 25 23:45:41 UTC 2021 , Edited by admin on Fri Jun 25 23:45:41 UTC 2021
PRIMARY RxNorm
EPA CompTox
657-24-9
Created by admin on Fri Jun 25 23:45:40 UTC 2021 , Edited by admin on Fri Jun 25 23:45:40 UTC 2021
PRIMARY