Metformin


Description

Metformin is an antihyperglycemic agent of the _biguanide_ class, used for the management of type II diabetes) [FDA label]. Currently, metformin is the first drug of choice for the management of type II diabetes and is prescribed to at least 120 mil...

Read more

Pharmacology

Indication

**Metformin tablet**

Metformin is indicated as an adjunct to diet and exercise to increase glyce...
Read more

Pharmacodynamic

**General effects**

Insulin is an important hormone that regulates blood glucose levels [
Read more

Mechanism of action


Metformin's mechanisms of action are unique from other classes of oral antihyperglycemic drugs. Me...
Read more

Absorption


**Regular tablet absorption**

The absolute bioavailability of a metformin 500 mg tablet adminis...
Read more

Protein binding

Metformin is negligibly bound to plasma proteins [FDA label], in contrast to sulfonylureas, which ar... Read more

Volume of distribution

The apparent volume of distribution (V/F) of metformin after one oral dose of metformin 850 mg avera... Read more

Clearance

Renal clearance is about 3.5 times greater than creatinine clearance, which indicates that tubular s... Read more

Half life

Approximately 6.2 hours in the plasma [FDA label] and in the blood, the elimination half-life is app... Read more

Route of elimination

This drug is substantially excreted by the kidney [FDA label].

Renal clearance of metformin is a...
Read more

Toxicity

**Metformin (hydrochloride) toxicity data**:

Oral LD50 (rat): 1 g/kg; Intraperitoneal LD50 (rat)...
Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Diarrhea US
  • Kind: experimental
    • Percent: 53.2%
  • Kind: placebo
    • Percent: 11.7%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 25.5%
  • Kind: placebo
    • Percent: 8.3%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 25.5%
  • Kind: placebo
    • Percent: 8.3%
  • Clinical Trial
    Flatulence US
  • Kind: experimental
    • Percent: 12.1%
  • Kind: placebo
    • Percent: 5.5%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 10
  • Kind: placebo
    • Percent: 3
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 9.2%
  • Kind: placebo
    • Percent: 5.5%
  • Clinical Trial
    Indigestion US
  • Kind: experimental
    • Percent: 7.1%
  • Kind: placebo
    • Percent: 4.1%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 7
  • Kind: placebo
    • Percent: 2
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 7
  • Kind: placebo
    • Percent: 2
  • Clinical Trial
    Abdominal Discomfort US
  • Kind: experimental
    • Percent: 6.4%
  • Kind: placebo
    • Percent: 4.8%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 5.7%
  • Kind: placebo
    • Percent: 4.8%
  • Clinical Trial
    Abnormal stools US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Hypoglycemia US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Myalgia US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Lightheadedness US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Dyspnea US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Nail disorders US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Increased sweating US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Taste Disorders US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Chest discomfort US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Chills US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Flu syndrome US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Flushing US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Palpitation US
  • Kind: experimental
    • Percent: 1-5
  • Clinical Trial
    Myalgia US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Hypoglycemia US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Dyspnea US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Light-headedness US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Abnoraml stools US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Chest discomfort US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Chills US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Flu-like Syndrome US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Flushing US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Nail disorder US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Increased sweating US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Taste Disorder US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Palpitation US
  • Kind: experimental
    • Percent: <5%
  • Clinical Trial
    Mixed hepatocellular liver injury US
    Post Marketing
    Hepatocellular liver injury US
    Post Marketing
    Cholestatic liver injury US
    Post Marketing
    Hypoglycemia US
    Varying Reports
    Vitamin B12 Deficiency US
    Clinical Trial
    Lactic Acidosis US
    Post Marketing

    Contraindications

    • Regions: US
    • Patient Conditions:
        • Name: Diabetic Ketoacidosis
        • Drugbank Id: DBCOND0000979
    • Regions: US
    • Patient Conditions:
        • Name: Diabetic Ketoacidosis
        • Drugbank Id: DBCOND0000979
    • Patient Conditions Associated With:
        • Name: Coma
        • Drugbank Id: DBCOND0017696
    • Regions: US
    • Patient Conditions:
        • Name: Hypersensitivity to metformin
        • Drugbank Id: DBCOND0118368
    • Regions: US
    • Patient Conditions:
        • Name: Severe Renal Impairment
        • Drugbank Id: DBCOND0045819
        • Modification Of:
          • Base:
            • Name: Renal Impairment
            • Drugbank Id: DBCOND0031781
          • Severity:
            • Includes:
              • severe
    • Patient Conditions Associated With:
        • Name: Estimated GFR <30mL/min
        • Drugbank Id: DBCOND0102261
    • Route:
      • Oral
    • Regions: US
    • Patient Conditions:
        • Name: Acute metabolic acidosis
        • Drugbank Id: DBCOND0107644
        • Modification Of:
          • Base:
            • Name: Metabolic Acidosis
            • Drugbank Id: DBCOND0043658
          • Severity:
            • Includes:
              • acute
    • Route:
      • Oral
    • Regions: US
    • Patient Conditions:
        • Name: Chronic metabolic acidosis
        • Drugbank Id: DBCOND0107645
        • Modification Of:
          • Base:
            • Name: Metabolic Acidosis
            • Drugbank Id: DBCOND0043658
          • Severity:
            • Includes:
              • chronic

    Food Interactions

    • Avoid alcohol.
    • Take with food to reduce gastric irritation.

    Interactions

    Type in a drug name to check for interaction with Metformin

    The risk or severity of hypoglycemia can be increased when Metformin is combined with 2,4-thiazolidinedione.
    The therapeutic efficacy of Metformin can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
    7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypoglycemic activities of Metformin.
    Metformin may decrease the excretion rate of Abacavir which could result in a higher serum level.
    The excretion of Abemaciclib can be decreased when combined with Metformin.
    The risk or severity of hypoglycemia can be increased when Acarbose is combined with Metformin.
    The therapeutic efficacy of Metformin can be increased when used in combination with Acebutolol.
    Aceclofenac may decrease the excretion rate of Metformin which could result in a higher serum level.
    Acemetacin may decrease the excretion rate of Metformin which could result in a higher serum level.
    The risk or severity of lactic acidosis can be increased when Acetazolamide is combined with Metformin.
    The risk or severity of hypoglycemia can be increased when Metformin is combined with Acetohexamide.
    The therapeutic efficacy of Metformin can be increased when used in combination with Acetyl sulfisoxazole.
    The serum concentration of Acetyldigoxin can be increased when it is combined with Metformin.
    The risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Metformin.
    Metformin may decrease the excretion rate of Aclidinium which could result in a higher serum level.
    Metformin may decrease the excretion rate of Acrivastine which could result in a higher serum level.
    Acyclovir may decrease the excretion rate of Metformin which could result in a higher serum level.
    Adefovir may decrease the excretion rate of Metformin which could result in a higher serum level.
    Adefovir dipivoxil may decrease the excretion rate of Metformin which could result in a higher serum level.
    The serum concentration of Agmatine can be increased when it is combined with Metformin.

    References

    • 1 . Witters LA: The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7. [PubMed: 11602616]
    • 2 . UNGAR G, FREEDMAN L, SHAPIRO SL: Pharmacological studies of a new oral hypoglycemic drug. Proc Soc Exp Biol Med. 1957 May;95(1):190-2. [PubMed: 13432032]
    • 3 . Lord JM, Flight IH, Norman RJ: Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003 Oct 25;327(7421):951-3. [PubMed: 14576245]
    • 4 . Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N: Metformin in non-alcoholic steatohepatitis. Lancet. 2001 Sep 15;358(9285):893-4. [PubMed: 11567710]
    • 5 . Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP: Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004 Jul 1;20(1):23-8. [PubMed: 15225167]
    • 6 . Rena G, Hardie DG, Pearson ER: The mechanisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-1585. doi: 10.1007/s00125-017-4342-z. Epub 2017 Aug 3. [PubMed: 28776086]
    • 7 . Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, Camporez JG, Cline GW, Butrico GM, Kemp BE, Casals G, Steinberg GR, Vatner DF, Petersen KF, Shulman GI: Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat Med. 2018 Jul 23. pii: 10.1038/s41591-018-0125-4. doi: 10.1038/s41591-018-0125-4. [PubMed: 30038219]
    • 8 . Lucis OJ: The status of metformin in Canada. Can Med Assoc J. 1983 Jan 1;128(1):24-6. [PubMed: 6847752]
    • 9 . Cameron AR, Logie L, Patel K, Erhardt S, Bacon S, Middleton P, Harthill J, Forteath C, Coats JT, Kerr C, Curry H, Stewart D, Sakamoto K, Repiscak P, Paterson MJ, Hassinen I, McDougall G, Rena G: Metformin selectively targets redox control of complex I energy transduction. Redox Biol. 2018 Apr;14:187-197. doi: 10.1016/j.redox.2017.08.018. Epub 2017 Aug 26. [PubMed: 28942196]
    • 10 . Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI: Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014 Jun 26;510(7506):542-6. doi: 10.1038/nature13270. Epub 2014 May 21. [PubMed: 24847880]
    • 11 . Rena G, Pearson ER, Sakamoto K: Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013 Sep;56(9):1898-906. doi: 10.1007/s00125-013-2991-0. Epub 2013 Jul 9. [PubMed: 23835523]
    • 12 . Lund SS, Tarnow L, Stehouwer CD, Schalkwijk CG, Frandsen M, Smidt UM, Pedersen O, Parving HH, Vaag A: Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial. Diabetes Obes Metab. 2007 May;9(3):394-407. doi: 10.1111/j.1463-1326.2007.00713.x. [PubMed: 17391168]
    • 13 . Proks P, Kramer H, Haythorne E, Ashcroft FM: Binding of sulphonylureas to plasma proteins - A KATP channel perspective. PLoS One. 2018 May 17;13(5):e0197634. doi: 10.1371/journal.pone.0197634. eCollection 2018. [PubMed: 29772022]
    • 14 . Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F: Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012 Mar;122(6):253-70. doi: 10.1042/CS20110386. [PubMed: 22117616]
    • 15 . Misra P, Chakrabarti R: The role of AMP kinase in diabetes. Indian J Med Res. 2007 Mar;125(3):389-98. [PubMed: 17496363]
    • 16 . Valsecchi F, Ramos-Espiritu LS, Buck J, Levin LR, Manfredi G: cAMP and mitochondria. Physiology (Bethesda). 2013 May;28(3):199-209. doi: 10.1152/physiol.00004.2013. [PubMed: 23636265]
    • 17 . Matthew J Crowley, MD, Clarissa J Diamantidis, MD, Jennifer R McDuffie, PhD, Blake Cameron, MD, John Stanifer, MD, Clare K Mock, MD, Andrzej Kosinski, PhD, Xianwei Wang, MD, Shuang Tang, MD, PhD, and John W Williams, Jr, MD, MHSc (2016). Metformin Use in Patients with Historical Contraindications or Precautions. Department of Veterans Affairs (US).
    • 18 . Institute for Quality and Efficiency in Health Care (IQWiG) (2008). Type 2 diabetes: Overview. InformedHealth.org.
    • 19 . Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program [Link]
    • 20 . UptoDate: Pathogenesis of type 2 diabetes mellitus [Link]
    • 21 . Comparing Dissolution Profiles of of Seven Metformin Formulations in Simulated Intestinal Fluid [File]
    • 22 . Glumetza FDA [File]
    • 23 . Metformin label [File]
    • 24 . Metformin Canadian monograph [File]
    • 25 . MedSafe NZ Metformin mylan [File]

    Recent Questions