Search References Drug Actions/Targets About Access data Feedback
Sign In
mitontu@gmail.com
2021 MitoTox | (CC BY-NC 4.0)
Drug

D0080 | Metformin

Molecular Formula C4H11N5
Molecular Weight 129.16
Structure
State solid
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 [FDA label].
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 [FDA label].
Route of elimination This drug is substantially excreted by the kidney [FDA label]. 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 [FDA label].
Protein binding Metformin is negligibly bound to plasma proteins [FDA label], in contrast to sulfonylureas, which are more than 90% protein bound [A176140].
Half life Approximately 6.2 hours in the plasma [FDA label] and in the blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution [FDA label].
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 [FDA label]. 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 [FDA label]. **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 [FDA label]. **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 [FDA label]. 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 [FDA label].
Trade names Fortamet, Glucophage, Glumetza
Description Antidiabetics; biguanide antihyperglycemic agent; insulin sensitizer

A

A10BD25 Metformin, saxagliptin and dapagliflozin


[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

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

A10BD22 Metformin and evogliptin


[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

A10BD20 Metformin and empagliflozin


[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

A10BD18 Metformin and gemigliptin


[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

A10BD17 Metformin and acarbose


[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

A10BD16 Metformin and canagliflozin


[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

A10BD15 Metformin and dapagliflozin


[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

A10BD14 Metformin and repaglinide


[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

A10BD13 Metformin and alogliptin


[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

A10BD11 Metformin and linagliptin


[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

A10BD10 Metformin and saxagliptin


[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

A10BD08 Metformin and vildagliptin


[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

A10BD07 Metformin and sitagliptin


[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

A10BD05 Metformin and pioglitazone


[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

A10BD03 Metformin and rosiglitazone


[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

A10BD02 Metformin and sulfonylureas


[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

A10BA02 Metformin


[A10BA] Biguanides


[A10B] BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS


[A10] DRUGS USED IN DIABETES


[A] Alimentary tract and metabolism

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 500 μM 24 hours human hepatocytes Measurement of mitochondrial membrane potential Negative 15
MEMBRANE POTENTIAL 1 mM 24 hours human hepatocytes Measurement of mitochondrial membrane potential decrease 15
MEMBRANE POTENTIAL 2 mM 24 hours human hepatocytes Measurement of mitochondrial membrane potential decrease 15
MEMBRANE POTENTIAL 388.4 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION > 400 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION 351.8 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. decrease EC20 36
STATE 2 RESPIRATION 500 nmol/mg mitochondrial protein rat; Sprague–Dawley liver mitochondria Meassurement of respiration Negative 15
STATE 2 RESPIRATION 500 nmol/mg mitochondrial protein 40 minutes preincubation rat; Sprague–Dawley liver mitochondria Meassurement of respiration decrease 15
STATE 3 RESPIRATION 2mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Measurement of Oxygen level; incubated in complex I substrate; added ADP (500 μM) decrease p < 0.05 172
STATE 3 RESPIRATION 2mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Measurement of Oxygen level; incubated in complex II substrate; added ADP (500 μM) Negative p < 0.05 172
STATE 3 RESPIRATION 500 nmol/mg mitochondrial protein rat; Sprague–Dawley liver mitochondria Meassurement of respiration Negative 15
STATE 3 RESPIRATION 500 nmol/mg mitochondrial protein 40 min preincubation rat; Sprague–Dawley liver mitochondria Meassurement of respiration decrease 15
STATE 4 RESPIRATION 2mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Measurement of Oxygen level; incubated in complex I substrate; added oligomycin (2.5 μg oligomycin/mg mitochondrial protein) decrease p < 0.05 172
STATE 4 RESPIRATION 2mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Measurement of Oxygen level; incubated in complex II substrate; added oligomycin (2.5 μg oligomycin/mg mitochondrial protein) Negative p < 0.05 172
OXYGEN CONSUMPTION RATE (OCR) 500 μM 24 hours human HepG2 cells Measurement of OCR Negative p < 0.001 15
MAXIMAL RESPIRATION 2mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Measurement of Oxygen level; incubated in complex I substrate; added FCCP (1.5 μM) decrease p < 0.05 172
MAXIMAL RESPIRATION 2mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Measurement of Oxygen level; incubated in complex II substrate; added FCCP (1.5 μM) Negative p < 0.05 172
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex V activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 0.05 mM 24 hours human MCF7 Meassurement of mitochondrial respiration Negative p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.5 mM 24 hours human MCF7 Meassurement of mitochondrial respiration Negative p < 0.05 172
ELECTRON TRANSPORT CHAIN 5 mM 24 hours human MCF7 Meassurement of mitochondrial respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.05 mM 24 hours human MCF7 Meassurement of coupled respiration Negative p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.5 mM 24 hours human MCF7 Meassurement of coupled respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 5 mM 24 hours human MCF7 Meassurement of coupled respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.5 mM 24 hours mouse NMuMG Meassurement of mitochondrial respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.5 mM 24 hours mouse NT2196 Meassurement of mitochondrial respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.5 mM 24 hours human MCF10A Meassurement of mitochondrial respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 0.5 mM 24 hours human MCF7 Meassurement of mitochondrial respiration decrease p < 0.05 172
ELECTRON TRANSPORT CHAIN 66 mM Bovine heart mitochondria Measurement of complex I activity decrease IC50 15
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN inhibit 197
UNCOUPLED RESPIRATION 0.05 mM 24 hours human MCF7 Meassurement of uncoupled respiration Negative p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours human MCF7 Meassurement of uncoupled respiration Negative p < 0.05 172
UNCOUPLED RESPIRATION 5 mM 24 hours human MCF7 Meassurement of uncoupled respiration Negative p < 0.05 172
UNCOUPLED RESPIRATION 0.05 mM 24 hours human MCF7 Meassurement of non-mitochondrial respiration Negative p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours human MCF7 Meassurement of non-mitochondrial respiration increase p < 0.05 172
UNCOUPLED RESPIRATION 5 mM 24 hours human MCF7 Meassurement of non-mitochondrial respiration increase p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours human MCF7 Meassurement of coupled respiration; Meassurement of uncoupled respiration; cells grown in glucose increase p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours human MCF7 Meassurement of coupled respiration; Meassurement of uncoupled respiration; cells grown in galactose increase p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours mouse NMuMG Meassurement of coupled respiration; Meassurement of uncoupled respiration increase p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours mouse NT2196 Meassurement of coupled respiration; Meassurement of uncoupled respiration Negative p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours human MCF10A Meassurement of coupled respiration; Meassurement of uncoupled respiration increase p < 0.05 172
UNCOUPLED RESPIRATION 0.5 mM 24 hours human MCF7 Meassurement of coupled respiration; Meassurement of uncoupled respiration Negative p < 0.05 172
GENERATION OF LACTATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of lactate concentration Negative p < 0.05 172
GENERATION OF LACTATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of lactate concentration increase p < 0.05 172
LACTATE TO PYRUVATE RATIO 0.5mM 24 hours human MCF7 Meassurement of lactate + pyruvate concentration; compared with MCF10A increase p < 0.05 172
LACTATE TO PYRUVATE RATIO 5.0mM 24 hours human MCF7 Meassurement of lactate + pyruvate concentration; compared with MCF10A increase p < 0.05 172
GENERATION OF CITRATE 0.5mM 24 hours human MCF10A Meassurement of citrate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF CITRATE 0.5mM 24 hours human MCF7 Meassurement of citrate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF CITRATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of citrate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF CITRATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of citrate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF ISOCITRATE 0.5mM 24 hours human MCF10A Meassurement of isocitrate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF ISOCITRATE 0.5mM 24 hours human MCF7 Meassurement of isocitrate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF ALPHA-KETOGLUTARATE 0.5mM 24 hours human MCF10A Meassurement of alpha-ketoglutarate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF ALPHA-KETOGLUTARATE 0.5mM 24 hours human MCF7 Meassurement of alpha-ketoglutarate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF ALPHA-KETOGLUTARATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of alpha-ketoglutarate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF ALPHA-KETOGLUTARATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of alpha-ketoglutarate concentration; compared with MCF10A affect p < 0.05 172
GENERATION OF SUCCINATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of succinate concentration decrease p < 0.05 172
GENERATION OF SUCCINATE 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of succinate concentration decrease p < 0.05 172
ECAR 500 μM 24 hours human HepG2 cells Measurement of ECAR Negative p < 0.001 15
GLUCOSE CONSUMPTION 5 mM 24 hours mouse NMuMG Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 24 hours mouse NT2196 Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 24 hours human MCF10A Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 24 hours human MCF7 Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 48 hours mouse NMuMG Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 48 hours mouse NT2196 Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 48 hours human MCF10A Meassurement of glucose concentration increase p < 0.05 172
GLUCOSE CONSUMPTION 5 mM 48 hours human MCF7 Meassurement of glucose concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 24 hours mouse NMuMG Meassurement of lactate concentration Negative p < 0.05 172
LACTATE PRODUCTION 5 mM 24 hours mouse NT2196 Meassurement of lactate concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 24 hours human MCF10A Meassurement of lactate concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 24 hours human MCF7 Meassurement of lactate concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 48 hours mouse NMuMG Meassurement of lactate concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 48 hours mouse NT2196 Meassurement of lactate concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 48 hours human MCF10A Meassurement of lactate concentration increase p < 0.05 172
LACTATE PRODUCTION 5 mM 48 hours human MCF7 Meassurement of lactate concentration increase p < 0.05 172
ATP SYNTHESIS 62.5 μM 24 hours human HepG2 cells Assay of Cellular ATP Content Negative p < 0.001 15
ATP SYNTHESIS 62.5 μM 24 hours human HepG2 cells Assay of Cellular ATP Content Negative p < 0.001 15
ATP SYNTHESIS 657 μM 24 hours human hepatocytes Assay of Cellular ATP Content decrease IC50 15
ATP SYNTHESIS 1430 μM 24 hours human HepG2 cells Assay of Cellular ATP Content decrease IC50 15
ATP SYNTHESIS > 2000 μM 24 hours human HepG2 cells Assay of Cellular ATP Content decrease IC50 15
SWELLING > 400 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36
OXIDATIVE STRESS 500 μM 24 hours human hepatocytes ROS measurement Negative 15
OXIDATIVE STRESS 1 mM 24 hours human hepatocytes ROS measurement increase 15
OXIDATIVE STRESS 2 mM 24 hours human hepatocytes ROS measurement increase 15
OXIDATIVE STRESS 500 μM 24 hours human hepatocytes Measurement of mitochondrial membrane potential Negative 15
OXIDATIVE STRESS 1 mM 24 hours human hepatocytes Measurement of mitochondrial membrane potential affect 15
OXIDATIVE STRESS 2 mM 24 hours human hepatocytes Measurement of mitochondrial membrane potential affect 15

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
NADH:ubiquinone reductase 66 mM Bovine heart mitochondria Measurement of complex I activity inhibitor IC50 15
NADH:ubiquinone reductase inhibitor 35
NADH:ubiquinone reductase > 400 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Succinate dehydrogenase 351.8 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. inhibit EC20 36
Quinol--cytochrome-c reductase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Cytochrome c oxidase 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ATP synthase 50 μM bovine heart mitochondria Measurement of complex V activity Negative p < 0.05 3
ATP 62.5 μM 24 hours human HepG2 cells Assay of Cellular ATP Content Negative p < 0.001 15
ATP 62.5 μM 24 hours human HepG2 cells Assay of Cellular ATP Content Negative p < 0.001 15
ATP 657 μM 24 hours human hepatocytes Assay of Cellular ATP Content decrease IC50 15
ATP 1430 μM 24 hours human HepG2 cells Assay of Cellular ATP Content decrease IC50 15
ATP > 2000 μM 24 hours human HepG2 cells Assay of Cellular ATP Content decrease IC50 15
lactate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of lactate concentration Negative p < 0.05 172
lactate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of lactate concentration increase p < 0.05 172
citrate 0.5mM 24 hours human MCF10A Meassurement of citrate concentration; compared with MCF10A decrease p < 0.05 172
citrate 0.5mM 24 hours human MCF7 Meassurement of citrate concentration; compared with MCF10A decrease p < 0.05 172
citrate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of citrate concentration; compared with MCF10A decrease p < 0.05 172
citrate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of citrate concentration; compared with MCF10A decrease p < 0.05 172
isocitrate 0.5mM 24 hours human MCF10A Meassurement of isocitrate concentration; compared with MCF10A decrease p < 0.05 172
isocitrate 0.5mM 24 hours human MCF7 Meassurement of isocitrate concentration; compared with MCF10A decrease p < 0.05 172
alpha-ketoglutarate 0.5mM 24 hours human MCF10A Meassurement of alpha-ketoglutarate concentration; compared with MCF10A decrease p < 0.05 172
alpha-ketoglutarate 0.5mM 24 hours human MCF7 Meassurement of alpha-ketoglutarate concentration; compared with MCF10A decrease p < 0.05 172
alpha-ketoglutarate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of alpha-ketoglutarate concentration; compared with MCF10A decrease p < 0.05 172
alpha-ketoglutarate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of alpha-ketoglutarate concentration; compared with MCF10A decrease p < 0.05 172
succinate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of succinate concentration decrease p < 0.05 172
succinate 5mM 30 minutes mouse; C57BL/6J isolated skeletal muscle mitochondria Meassurement of succinate concentration decrease p < 0.05 172
Reactive oxygen species 500 μM 24 hours human hepatocytes ROS measurement Negative 15
Reactive oxygen species 1 mM 24 hours human hepatocytes ROS measurement increase 15
Reactive oxygen species 2 mM 24 hours human hepatocytes ROS measurement increase 15
oxidized glutathione 500 μM 24 hours human hepatocytes Measurement of mitochondrial membrane potential Negative 15
oxidized glutathione 1 mM 24 hours human hepatocytes Measurement of mitochondrial membrane potential decrease 15
oxidized glutathione 2 mM 24 hours human hepatocytes Measurement of mitochondrial membrane potential decrease 15
Cytochrome c > 800 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Warning

Aggregated GHS information provided by 3 companies from 2 notifications to the ECHA C&L Inventory.


Reported as not meeting GHS hazard criteria by 2 of 3 companies. For more detailed information, please visit ECHA C&L website


Of the 1 notification(s) provided by 1 of 3 companies with hazard statement code(s):


H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P264, P270, P301+P312, P330, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]


H315: Causes skin irritation [Warning Skin corrosion/irritation]


H319: Causes serious eye irritation [Warning Serious eye damage/eye irritation]


 P264, P270, P280, P301+P312, P302+P352, P305+P351+P338, P321, P330, P332+P313, P337+P313, P362, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
mouse LD50 intraperitoneal > 4gm/kg (4000mg/kg) Acta Pharmacologica et Toxicologica. Vol. 8, Pg. 329, 1952.
mouse LD50 oral > 10gm/kg (10000mg/kg) Toksikologicheskii Vestnik. Vol. (4), Pg. 39, 1998.
rat LDLo unreported 600mg/kg (600mg/kg) Biochemical Pharmacology. Vol. 14, Pg. 1325, 1965.
rat LD oral > 500mg/kg (500mg/kg) National Academy of Sciences, National Research Council, Chemical-Biological Coordination Center, Review. Vol. 5, Pg. 17, 1953.
rabbit LD50 intraperitoneal > 3gm/kg (3000mg/kg) Acta Pharmacologica et Toxicologica. Vol. 8, Pg. 329, 1952.

  • Acute coronary syndrome

  • Blood glucose decreased

  • Coma

  • Diabetic ketoacidosis

  • Fasting

  • Hyperglycaemia

  • Hypersensitivity

  • Ketosis

  • Lactic acidosis

  • Metabolic acidosis

  • Myocardial infarction

  • Obesity

  • Type 1 diabetes mellitus

  • Type 2 diabetes mellitus

  • Weight decreased

  • Abdominal discomfort

  • Abdominal distension

  • Abdominal pain

  • Asthenia

  • Constipation

  • Diarrhoea

  • Dysgeusia

  • Dyspepsia

  • Flatulence

  • Gastrointestinal disorder

  • Gastrointestinal pain

  • Headache

  • Hypoglycaemia

  • Infection

  • Injury

  • Nausea

  • Rhinitis

  • Vomiting

    • 1,1-Dimethyl biguanide 1,1-Dimethylbiguanide 1-[(E)-amino(dimethylamino)methylidene]guanidine
    1-[(diaminomethylidene)amino]-N,N-dimethylmethanimidamide 1-carbamimidamido-N,N-dimethylmethanimidamide 15673-EP2269977A2
    15673-EP2269989A1 15673-EP2270007A1 15673-EP2270011A1
    15673-EP2272825A2 15673-EP2272834A1 15673-EP2272841A1
    15673-EP2275108A1 15673-EP2275414A1 15673-EP2280001A1
    15673-EP2287165A2 15673-EP2287166A2 15673-EP2292228A1
    15673-EP2292620A2 15673-EP2295406A1 15673-EP2295409A1
    15673-EP2295411A1 15673-EP2295422A2 15673-EP2298742A1
    15673-EP2298769A1 15673-EP2298772A1 15673-EP2298776A1
    15673-EP2298779A1 15673-EP2301533A1 15673-EP2301923A1
    15673-EP2301929A1 15673-EP2301935A1 15673-EP2301936A1
    15673-EP2305648A1 15673-EP2305674A1 15673-EP2308839A1
    15673-EP2308847A1 15673-EP2308878A2 15673-EP2314576A1
    15673-EP2314588A1 15673-EP2316470A2 3-(diaminomethylene)-1,1-dimethyl-guanidine;hydrochloride
    3-(diaminomethylidene)-1,1-dimethylguanidine 3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride 3-[bis(azanyl)methylidene]-1,1-dimethyl-guanidine;hydrochloride
    3-carbamimidoyl-1,1-dimethyl-guanidine 657-24-9 657M249
    9100L32L2N A19551 AB2000590
    AKOS000121065 AKOS005206848 AKOS015966566
    AS-65365 BBL012337 BDBM50229665
    BDBM57047 BIDD:GT0697 BIGUANIDE, 1,1-DIMETHYL-
    BPBio1_000009 BRD-K79602928-003-04-1 BRD-K79602928-003-08-2
    BSPBio_000007 BSPBio_002314 C07151
    C4H11N5 CAS-1115-70-4 CAS-657-24-9
    CCG-102605 CCRIS 9321 CHEBI:6801
    CHEMBL1431 CS-0009563 CTK2F2882
    D04966 DB00331 DMBG
    DMGG DSSTox_CID_3270 DSSTox_GSID_23270
    DSSTox_RID_76950 DTXSID2023270 Diabex
    Dianben Dimethylbiguanid Dimethylbiguanide
    Dimethyldiguanide Dimethylguanylguanidine EINECS 211-517-8
    FT-0628266 Fluamine Flumamine
    GTPL4503 GTPL4779 Glifage
    Gliguanid Glucophage Glucophage (Salt/Mix)
    Glumetza HMS2089D19 HSCI1_000295
    Haurymelin Imidodicarbonimidic diamide, N,N-dimethyl- Imidodicarbonimidic diamide-, N,N-dimethyl-
    Imidodicarbonimidicdiamide, N,N-dimethyl- Islotin K070
    KBio2_002310 KBio2_004878 KBio2_007446
    KBio3_002790 KBioGR_002310 KBioSS_002312
    LA 6023 (Salt/Mix) LA-6023 LS-43899
    MCULE-7393156510 MF8 MLS000028493
    Melbin Metformin (USAN/INN) Metformin [USAN:INN:BAN]
    Metformin base Metformina Metformina [DCIT]
    Metformina [Spanish] Metformine Metformine [INN-French]
    Metforminum Metforminum [INN-Latin] Metiguanide
    N,N-Dimethylbiguanide N,N-Dimethyldiguanide N,N-Dimethylguanylguanidin
    N,N-dimethylimidodicarbonimidic diamide N-dimethylbiguanide N1,N1-Dimethylbiguanide
    NCGC00016564-01 NCGC00016564-02 NCGC00016564-03
    NCGC00016564-05 NCGC00016564-07 NCGC00188959-01
    NCGC00255255-01 NNDG Obimet
    Prestwick0_000004 Prestwick1_000004 Prestwick2_000004
    Prestwick3_000004 Q19484 SBI-0206876.P001
    SC-73311 SCHEMBL10276396 SCHEMBL8944
    SCHEMBL9913821 SMR000058277 SPBio_001928
    STK011633 STL483693 STL484070
    Siofor Tox21_302370 UNII-9100L32L2N
    W-109589 XZWYZXLIPXDOLR-UHFFFAOYSA-N ZINC12859773
    [14C]-metformin [14C]metformin cMAP_000016
    cid_14219 metformin n',n'-dimethylbiguanide
    {[amino(dimethylamino)methylidene]amino}methanimidamide

    DrugBank Name Metformin
    DrugBank DB00331
    CAS Number 1115-70-4, 461-58-5, 4931-70-8, 657-24-9
    PubChem Compound 4091
    KEGG Compound ID C07151
    KEGG Drug D04966
    PubChem.Substance 46507752
    ChEBI 6801
    PharmGKB PA450395
    ChemSpider 3949
    BindingDB 50229665.0
    TTD DAP000205
    Wikipedia Metformin
    HET MF8
    DPD 10147

    1. Chan et al. (2005)
    2. Brunmair et al. (2004)
    3. Vuda et al. (2016)