Details of the Drug

General Information of Drug (ID: DM89QE1)

Drug Name
Metformin
Synonyms
657-24-9; 1,1-Dimethylbiguanide; N,N-dimethylimidodicarbonimidic diamide; Metiguanide; Dimethylbiguanide; Glucophage; Haurymelin; Gliguanid; Fluamine; Glumetza; Flumamine; Melbin; Diabex; N,N-Dimethylbiguanide; Metformina; Metforminum; Metformine; Islotin; Glifage; Siofor; N1,N1-Dimethylbiguanide; DMGG; NNDG; Dimethyldiguanide; N,N-Dimethyldiguanide; Metformina [DCIT]; Imidodicarbonimidic diamide, N,N-dimethyl-; Metformina [Spanish]; Metforminum [INN-Latin]; Metformine [INN-French]; Metformin [USAN:INN:BAN]; 1,1-Dimethyl; Diabetosan; Dimethylbiguanidine; Dimethylguanylguanidine; Glycon; Diabex (TN); Diaformin (TN); Dianben (TN); Fortamet (TN); Gen-Metformin; Glucophage (TN); Glumetza (TN); LA-6023; Nu-Metformin; Obimet (TN); Riomet (TN); Metformin (USAN/INN); 1,1-Dimethyl biguanide; 3-(diaminomethylidene)-1,1-dimethylguanidine; [14C]metformin
Indication
Disease Entry ICD 11 Status REF
Colorectal carcinoma N.A. Approved [1]
Non-insulin dependent diabetes 5A11 Approved [1]
Ovarian serous cystadenocarcinoma N.A. Approved [1]
Prostate carcinoma N.A. Approved [1]
Type-2 diabetes 5A11 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [3]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Hypoglycemic Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 129.16
Logarithm of the Partition Coefficient (xlogp) -1.3
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 1
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Clearance
The drug present in the plasma can be removed from the body at the rate of 7.4 mL/min/kg [5]
Elimination
99% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 1.7 hours [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 387.09946 micromolar/kg/day [6]
Unbound Fraction
The unbound fraction of drug in plasma is 1% [5]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.64 L/kg [5]
Chemical Identifiers
Formula
C4H11N5
IUPAC Name
3-(diaminomethylidene)-1,1-dimethylguanidine
Canonical SMILES
CN(C)C(=N)N=C(N)N
InChI
InChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
InChIKey
XZWYZXLIPXDOLR-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4091
ChEBI ID
CHEBI:6801
CAS Number
657-24-9
DrugBank ID
DB00331
TTD ID
D0D7LA
VARIDT ID
DR00133
ACDINA ID
D00405
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Acetyl-CoA carboxylase 2 (ACACB) TTY84UG ACACB_HUMAN Activator [7]
Solute carrier family 47 member 1 (SLC47A1) TTMHCGA S47A1_HUMAN Modulator [8]
HUMAN mannose receptor (MRC1) TTKV8W5 MRC1_HUMAN Inhibitor [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Equilibrative nucleoside transporter 4 (SLC29A4) DT3EAQP S29A4_HUMAN Substrate [9]
Thiamine transporter 1 (SLC19A2) DTLA4Q2 S19A2_HUMAN Substrate [10]
Thiamine transporter 2 (SLC19A3) DT39CEA S19A3_HUMAN Substrate [10]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [11]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [12]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [13]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [14]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [15]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [12]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Metformin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Gilteritinib DMTI0ZO Moderate Decreased clearance of Metformin due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [16]
Nifedipine DMSVOZT Moderate Altered absorption of Metformin caused by Nifedipine. Angina pectoris [BA40] [17]
Iodipamide DMXIQYS Major Decreased renal excretion of Metformin caused by Iodipamide mediated nephrotoxicity. Cholelithiasis [DC11] [18]
Amiloride DMRTSGP Moderate Decreased renal excretion of Metformin caused by Amiloride. Heart failure [BD10-BD1Z] [17]
Rifampin DMA8J1G Moderate Accelerated clearance of Metformin due to the transporter induction by Rifampin. HIV-infected patients with tuberculosis [1B10-1B14] [16]
Crizotinib DM4F29C Moderate Decreased clearance of Metformin due to the transporter inhibition by Crizotinib. Lung cancer [2C25] [16]
Porfimer Sodium DM7ZWNY Moderate Increased risk of photosensitivity reactions by the combination of Metformin and Porfimer Sodium. Lung cancer [2C25] [19]
Capmatinib DMYCXKL Moderate Decreased clearance of Metformin due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [20]
Risdiplam DMIMF8J Moderate Decreased clearance of Metformin due to the transporter inhibition by Risdiplam. Muscular atrophy [8B61] [16]
Olaparib DM8QB1D Moderate Decreased clearance of Metformin due to the transporter inhibition by Olaparib. Ovarian cancer [2C73] [16]
Pitolisant DM8RFNJ Moderate Decreased clearance of Metformin due to the transporter inhibition by Pitolisant. Somnolence [MG42] [21]
⏷ Show the Full List of 11 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 2 E00446 2723854 Colorant
Isopropyl alcohol E00070 3776 Antimicrobial preservative; Solvent
Quinoline yellow WS E00309 24671 Colorant
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Stearic acid E00079 5281 Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Ammonia E00007 222 Alkalizing agent
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Carbonic acid disodium salt E00199 10340 Alkalizing agent; Buffering agent; Diluent; Dispersing agent
Carboxymethylcellulose sodium E00621 Not Available Adsorbent; Binding agent; Disintegrant; Emulsifying agent; Suspending agent; Viscosity-controlling agent
Carmellose sodium E00625 Not Available Disintegrant
Crospovidone E00626 Not Available Disintegrant
Dextrin E00359 62698 Binding agent; Diluent; Microencapsulating agent; Stiffening agent; Suspending agent; Viscosity-controlling agent
Dibutyl sebacate E00160 7986 Plasticizing agent
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Glyceryl behenate E00481 5362585 Binding agent; Coating agent; Flavoring agent; Modified-release agent; Viscosity-controlling agent; lubricant
Glyceryl dibehenate E00537 22477175 Binding agent; Coating agent; Flavoring agent; Modified-release agent; Viscosity-controlling agent; lubricant
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Magnesium trisilicate E00477 5311266 Glidant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 400 E00653 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 6000 E00655 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium citrate dihydrate E00369 71474 Alkalizing agent; Buffering agent; Complexing agent; Emulsifying agent
Soybean lecithin E00637 Not Available Other agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Triethyl citrate E00128 6506 Plasticizing agent; Solvent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
⏷ Show the Full List of 37 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Metformin 500 mg tablet 500 mg Modified 24 HR Extended Release Oral Tablet Oral
Metformin 1000 mg tablet 1000 mg Modified 24 HR Extended Release Oral Tablet Oral
Metformin 1 mg tablet 1 mg Oral Tablet Oral
Metformin 1000 mg tablet 1000 mg Osmotic 24 HR Extended Release Oral Tablet Oral
Metformin 500 mg tablet 500 mg Osmotic 24 HR Extended Release Oral Tablet Oral
Metformin 500 mg tablet 500 mg 24 HR Extended Release Tablet Oral
Metformin 750 mg tablet 750 mg 24 HR Extended Release Tablet Oral
Metformin 750 mg tablet 750 mg 24 HR Extended Release Oral Tablet Oral
Metformin 500 mg tablet 500 mg 24 HR Extended Release Oral Tablet Oral
Metformin 1000 mg tablet 1000 mg Oral Tablet Oral
Metformin 500 mg tablet 500 mg Oral Tablet Oral
Metformin 850 mg tablet 850 mg Oral Tablet Oral
Metformin Hydrochloride 500mg extended release tablet 500mg Extended Release Tablet Oral
Metformin Hydrochloride 500mg tablet 500mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Metformin FDA Label
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. March 2020
4 BDDCS applied to over 900 drugs
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7 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.
8 Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res. 2006 Aug;23(8):1696-701.
9 Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66.
10 Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm. 2015 Dec 7;12(12):4301-10.
11 Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009 Oct;50(4):1227-40.
12 Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
13 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.
14 Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
15 Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin. Am J Obstet Gynecol. 2010 Apr;202(4):383.e1-7.
16 Cerner Multum, Inc. "Australian Product Information.".
17 Product Information. Glucophage (metformin). Bristol-Myers Squibb, Princeton, NJ.
18 Assan R, Heuclin C, Ganeval D, Bismuth C, George J, Girard JR "Metformin-induced lactic acidosis in the presence of acute renal failure." Diabetologia 13 (1977): 211-7. [PMID: 406158]
19 Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
20 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
21 Cerner Multum, Inc. "UK Summary of Product Characteristics.".