pharmacopeia
GET
/api/v1/drug/metformin

Boxed warning

WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin­ associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin­ associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1) ]. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.3), (2.7 ) , C ontraindications (4) , Warnings and Precautions (5.1) ].

2D structure
3-(diaminomethylidene)-1,1-dimethylguanidine
SMILES CN(C)C(=N)N=C(N)N
InChIKey XZWYZXLIPXDOLR-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, 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.

Insulin Receptor

Indications

Sourced from openFDA
  • & USAGE Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. Metformin hydrochloride tablets are biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.ICD-10: E11.9

Contraindications

Sourced from openFDA
  • Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [ see Warnings and Precautions (5.1) ]. Hypersensitivity to metformin.contraindicated

Dosage & administration

Sourced from openFDA

DOSAGE & ADMINISTRATION Adult Dosage for metformin hydrochloride tablets: Starting dose: 500 mg orally twice a day or 850 mg once a day, with meals ( 2.1 ) Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks, up to a maximum dose of 2550 mg per day, given in divided doses ( 2.1 ) Doses above 2000 mg may be better tolerated given 3 times a day with meals ( 2.1 ) Pediatric Dosage for metformin hydrochloride tablets: Starting dose: 500 mg orally twice a day, with meals ( 2.2 ) Increase dosage in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses twice daily ( 2.2 ) Renal Impairment: Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR) ( 2.3 ) Do not use in patients with eGFR below 30 mL/minute/1.73 m 2 ( 2.3 ) Initiation is not recommended in patients with eGFR between 30 to 45 mL/minute/1.73 m 2 ( 2.3 ) Assess risk/benefit of continuing if eGFR falls below 45 mL/minute/1.73 m 2 ( 2.3 ) Discontinue if eGFR falls below 30 mL/minute/1.73 m 2 ( 2.3 ) 2.1 Adult Dosage Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2550 mg per day, given in divided doses. Doses above 2000 mg may be better tolerated given 3 times a day with meals.

Warnings & precautions

Sourced from openFDA

Lactic Acidosis: See boxed warning. ( 5.1 ) Vitamin B 12 Deficiency: Metformin may lower vitamin B12 levels. Measure hematological parameters annually and vitamin B12 at 2 to 3 year intervals and manage any abnormalities. ( 5.2 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required ( 5.3 ) 5.1 Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin­ associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride tablets.

Adverse reactions

Sourced from openFDA

The following adverse reactions are also discussed elsewhere in the labeling: Lactic Acidosis [ see Boxed Warning and Warnings and Precautions (5.1) ]. Vitamin B12 Deficiency [ see Warnings and Precautions (5.2) ]. Hypoglycemia [ see Warnings and Precautions (5.3) For metformin hydrochloride tablets, the most common adverse reactions (>5.0%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Granules Pharmaceuticals Inc at 1-877-770-3183 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Metformin Hydrochloride Tablets In a U.S. clinical trial of metformin hydrochloride tablets in patients with type 2 diabetes mellitus, a total of 141 patients received metformin hydrochloride tablets up to 2550 mg per day. Adverse reactions reported in greater than 5% of metformin hydrochloride tablets treated patients and that were more common than in placebo-treated patients, are listed in Table 1.

Use in specific populations

Sourced from openFDA

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. ( 8.3 ) Geriatric Use: Assess renal function more frequently. ( 8.5 ) Hepatic Impairment: Avoid use in patients with hepatic impairment. ( 8.7 ) 8.1 Pregnancy Risk Summary Limited data with metformin hydrochloride tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data ] . There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see Clinical Considerations ] . No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 2- and 5-times, respectively, a 2550 mg clinical dose, based on body surface area [see Data ] . The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes mellitus with an HbA1C >7 and has been reported to be as high as 20 to 25% in women with a HbA1C > 10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S.

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption The absolute bioavailability of a metformin hydrochloride tablets 500 mg given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of metformin hydrochloride tablets 500 to 1500 mg and 850 to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination.

Overdosage

Sourced from openFDA

Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1) ] . Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.

Approval history

Sourced from openFDA
  • Sep 11, 2003NDANDA021591Ranbaxy
  • Jun 3, 2005NDANDA021748Santarus Inc
  • Aug 29, 2005NDANDA021842Takeda Pharms Usa
  • Mar 30, 2007NDANDA022044Msd Sub Merck
  • Jan 30, 2012NDANDA201281Boehringer Ingelheim
  • Feb 2, 2012NDANDA202270Msd Sub Merck
  • Jan 25, 2013NDANDA203414Takeda Pharms Usa
  • Aug 8, 2014NDANDA204353Janssen Pharms

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
433,189 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Nausea29,7266.9%
  2. 2Diarrhoea27,7116.4%
  3. 3Blood Glucose Increased27,4856.3%
  4. 4Drug Ineffective22,4195.2%
  5. 5Fatigue21,1854.9%
  6. 6Vomiting19,2224.4%
  7. 7Lactic Acidosis18,8134.3%
  8. 8Acute Kidney Injury17,8074.1%
  9. 9Weight Decreased17,3624.0%
  10. 10Dyspnoea16,4723.8%
  11. 11Dizziness15,6293.6%
  12. 12Off Label Use15,2603.5%
  13. 13Headache14,8853.4%
  14. 14Pain14,0673.2%
  15. 15Asthenia13,2383.1%

Literature

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Recent PubMed references pinned to Metformin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 3,070 ClinicalTrials.gov registrations naming Metformin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Metformin. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

  • C11orf65CPIC D (provisional)ClinPGx 4

Frequently asked questions

How does Metformin work?
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, 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.
What is Metformin used for?
According to FDA labeling, Metformin carries indications including: & USAGE Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. Metformin hydrochloride tablets are biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Metformin?
Metformin is classified as Biguanides, Biguanide, Insulin Receptor Agonists, Decreased Gluconeogenesis, Decreased Glycogenesis, Increased Glucose Transport into Cells.
What are the brand names for Metformin?
Metformin is marketed under brand names including Actoplus Met, Glucophage, Glumetza, Invokamet, Janumet, Jentadueto, Kazano, Kombiglyze.
What are the contraindications for Metformin?
Metformin labeling lists contraindications including: Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [ see Warnings and Precautions (5.1) ]. Hypersensitivity to metformin.. Always consult the full prescribing information and a clinician.
Note. Data for metformin is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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