General
Preferred name
METFORMIN
Synonyms
METFORMIN HYDROCHLORIDE ()
1,1-Dimethylbiguanide hydrochloride ()
Metformin HCl ()
1, 1-Dimethylbiguanide hydrochloride ()
Janumet-metformin hydrochloride ()
Metformin HCl ()
Metformin (hydrochloride) ()
metformin, buccal, Generex ()
1,1-Dimethylbiguanide (hydrochloride) ()
1,1-Dimethylbiguanide ()
1,1-Dimethylbiguanide HCl ()
Glucamet 850 ()
Metsol ()
NSC-91485 ()
Diagemet XL ()
Glucophage Xr ()
Metabet SR ()
Orabet ()
Milform ()
Diabefagos ()
Glucient SR ()
Apophage ()
Bolamyn SR ()
Neodipa ()
Ledermetin ()
Glucamet 500 ()
Glucophage SR ()
Janumet ()
Riomet er ()
Benofomin ()
Fortamet ()
EX404 ()
Glucaminol ()
Glucophage ()
Riomet ()
Sukkarto SR ()
Glumetza ()
EX-404 ()
Glyformin ()
Diabex ()
Walaphage ()
Siamformet ()
LA-6023 ()
Metformin extended release ()
Metformin-d6 (hydrochloride?) ()
P&D ID
PD010095
CAS
657-24-9
1115-70-4
1185166-01-1
Tags
natural product
drug
available
Approved by
PMDA
EMA
FDA
First approval
1961
1995
Drug Status
approved
Drug indication
Coronavirus Disease 2019 (COVID-19)
Antidiabetic
Type-2 diabetes
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Marketed formulations contain metformin hydrochloride (PubChem CID 14219). Metformin is often given in fixed-dose combinations with other antihyperglycemic agents.
METABOLISM
Intravenous studies using a single dose of metformin in normal subjects show that metformin is excreted as unchanged drug in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) or biliary excretion [FDA label].
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].
INDICATION
**Metformin tablet** Metformin is indicated as an adjunct to diet and exercise to increase glycemic control in _adults and pediatric patients_ 10 years of age and older diagnosed with type 2 diabetes mellitus [FDA label]. **Metformin extended-release tablet (XR)** The extended-release form is indicated as an adjunct to diet and exercise to improve glycemic control in only _adults_ with type 2 diabetes mellitus. Safety in children has not been determined to this date [FDA label].
ROE
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].
PHARMACODYNAMICS
**General effects**; ; Insulin is an important hormone that regulates blood glucose levels [T514]. Type II diabetes is characterized by a decrease in sensitivity to insulin, resulting in eventual elevations in blood glucose when the pancreas can no longer compensate. In patients diagnosed with type 2 diabetes, insulin no longer exerts adequate effects on tissues and cells (called insulin resistance) [T514] and insulin deficiency may also be present [L5753].; ; Metformin reduces liver (hepatic) production of glucose, decreases the intestinal absorption of glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization. In contrast with drugs of the _sulfonylurea_ class, which lead to hyperinsulinemia, the secretion of insulin is unchanged with metformin use [FDA label].; ; **Effect on fasting plasma glucose (FPG) and Glycosylated hemoglobin (HbA1c)**; ; HbA1c is an important periodic measure of glycemic control that is used to monitor diabetic patients. Fasting plasma glucose is also a useful and important measure of glycemic control. In a 29-week clinical trial of subjects diagnosed with type II diabetes, metformin decreased the fasting plasma glucose levels by an average of 59 mg/dL from baseline, compared to an average increase of 6.3 mg/dL from baseline in subjects taking a placebo [FDA label]. Glycosylated hemoglobin (HbA1c) was decreased by about 1.4% in subjects receiving metformin, and increased by 0.4% in subjects receiving placebo only [FDA label].
INDICATION
**Metformin tablet**; ; Metformin is indicated as an adjunct to diet and exercise to increase glycemic control in _adults and pediatric patients_ 10 years of age and older diagnosed with type 2 diabetes mellitus [FDA label].; ; **Metformin extended-release tablet (XR)**; ; The extended-release form is indicated as an adjunct to diet and exercise to improve glycemic control in only _adults_ with type 2 diabetes mellitus. Safety in children has not been determined to this date [FDA label].
ROE
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].
PHARMACODYNAMICS
**General effects** Insulin is an important hormone that regulates blood glucose levels [T514]. Type II diabetes is characterized by a decrease in sensitivity to insulin, resulting in eventual elevations in blood glucose when the pancreas can no longer compensate. In patients diagnosed with type 2 diabetes, insulin no longer exerts adequate effects on tissues and cells (called insulin resistance) [T514] and insulin deficiency may also be present [L5753]. Metformin reduces liver (hepatic) production of glucose, decreases the intestinal absorption of glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization. In contrast with drugs of the _sulfonylurea_ class, which lead to hyperinsulinemia, the secretion of insulin is unchanged with metformin use [FDA label]. **Effect on fasting plasma glucose (FPG) and Glycosylated hemoglobin (HbA1c)** HbA1c is an important periodic measure of glycemic control that is used to monitor diabetic patients. Fasting plasma glucose is also a useful and important measure of glycemic control. In a 29-week clinical trial of subjects diagnosed with type II diabetes, metformin decreased the fasting plasma glucose levels by an average of 59 mg/dL from baseline, compared to an average increase of 6.3 mg/dL from baseline in subjects taking a placebo [FDA label]. Glycosylated hemoglobin (HbA1c) was decreased by about 1.4% in subjects receiving metformin, and increased by 0.4% in subjects receiving placebo only [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].
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].
DESCRIPTION
Marketed formulations contain metformin hydrochloride (PubChem CID 14219). Metformin is often given in fixed-dose combinations with other antihyperglycemic agents.
Repurposing: Cancer cells undergo a metabolic switch to aerobic glycolysis, and become reliant on this metabolic pathway for energy (the Warburg effect). Inhibition of the glycolytic pathway is therefore considered as a tractable therapeutic target in oncology. As metformin is an inhibitor of glycolysis it is being examined for anti-cancer effects in a number of malignancies. Similarly, it is being examined for anti-inflammatory potential since activated immune cells also undergo a metabolic switch to aerobic glycolysis. If found to be effective, this could ultimately lead to metformin being repurposed for indications other than type 2 diabetes. (GtoPdb)
Repurposing: Cancer cells undergo a metabolic switch to aerobic glycolysis, and become reliant on this metabolic pathway for energy (the Warburg effect). Inhibition of the glycolytic pathway is therefore considered as a tractable therapeutic target in oncology. As metformin is an inhibitor of glycolysis it is being examined for anti-cancer effects in a number of malignancies. Similarly, it is being examined for anti-inflammatory potential since activated immune cells also undergo a metabolic switch to aerobic glycolysis. If found to be effective, this could ultimately lead to metformin being repurposed for indications other than type 2 diabetes. (GtoPdb)
DESCRIPTION
Potent and selective inhibitor of iNOS
(Tocris Bioactive Compound Library)
DESCRIPTION
Activator of LKB1/AMPK; antidiabetic agent
(Tocriscreen Plus)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
3
Organisms
1
Compound Sets
31
AdooQ Bioactive Compound Library
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
84
Molecular Weight
129.1
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
4
Rotatable Bonds
0
Ring Count
0
Aromatic Ring Count
0
cLogP
-1.03
TPSA
88.99
Fraction CSP3
0.5
Chiral centers
0.0
Largest ring
0.0
QED
0.25
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
MOA
non-specific serine-threonine protein kinase activator
Activator
inhibitor of mitochondrial complex I of the electron transport chain
AMP-Activated Protein Kinase (AMPK) Activators
MTTP Inhibitor
mitochondrial repiratory chain 1 inhibitors
adenine deaminase inhibitor
GPD2 gene modulator
insulin sensitizer
Target
Mitochondrial complex I (NADH dehydrogenase)
Mitochondrial glycerol-3-phosphate dehydrogenase
AMPK
ACACB, PRKAB1
Mitophagy
Autophagy,Carbohydrate Metabolism,JNK,Mitophagy,p38 MAPK
AMPK,Apoptosis related,JNK,Mitophagy,p38 MAPK
Pathway
PI3K/Akt/mTOR signaling
Autophagy
Epigenetics
PI3K/Akt/mTOR
Member status
member
Indication
diabetes mellitus
Biosynthetic Origin
Alkaloid
Therapeutic Indication
Antidiabetic
Therapeutic Class
Metabolic Disorders
Hypoglycemic Agents
Antiviral Agents
Source data
