Description

Simple

A medication used with diet and exercise to control blood sugar in diabetes and is sometimes used to control high blood sugar in a disease called polycystic ovary syndrome (or PCOS).

Clinical

A biguanide drug used in conjunction with diet and exercise for glycemic control in type 2 diabetes mellitus and used off-label for insulin resistance in polycystic ovary syndrome (PCOS).

Overview

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 million people worldwide [14].

Metformin is considered an antihyperglycemic drug because it lowers blood glucose concentrations in type II diabetes without causing hypoglycemia. Metformin is commonly described as an _insulin sensitizer_ leading to a decrease in insulin resistance and a clinically significant reduction of plasma fasting insulin levels [14]. Another well-known benefit of this drug is modest weight loss. Metformin is the drug of choice for obese type II diabetes patients [Read more

Pharmacology

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... Read more

Pharmacodynamic

**General effects**

Insulin is an important hormone that regulates blood glucose levels [18]. Type II diabetes is characte... Read more

Mechanism of action


Metformin's mechanisms of action are unique from other classes of oral antihyperglycemic drugs. Metformin decreases blood glucose levels by decreasing hepatic glucose production (gluconeogenesis), decreasing the intestinal absorption of glucose, and increasing insulin sensitivity by increasing per... Read more

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 incr... Read more

Protein binding

Metformin is negligibly bound to plasma proteins [FDA label], in contrast to sulfonylureas, which are more than 90% protein bound [ Read more

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].

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].

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].

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 eli... Read more

Toxicity

**Metformin (hydrochloride) toxicity data**:

Oral LD50 (rat): 1 g/kg; Intraperitoneal LD50 (rat): 500 mg/kg; Subcutaneous LD50 (rat): 300 mg/kg; Oral LD50 (mouse): 1450 mg/kg; Intraperitoneal LD50 (mouse): 420 mg/kg; Subcutaneous LD50 (mouse): 225 mg/kg [MSDS].

**A note on lactic acidosis**... Read more

Adverse Effects

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
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2,4-thiazolidinedione
The risk or severity of hypoglycemia can be increased when Metformin is combined with 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinoline
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
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypoglycemic activities of Metformin.
Abacavir
Metformin may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abemaciclib
The excretion of Abemaciclib can be decreased when combined with Metformin.
Acarbose
The risk or severity of hypoglycemia can be increased when Acarbose is combined with Metformin.
Acebutolol
The therapeutic efficacy of Metformin can be increased when used in combination with Acebutolol.
Aceclofenac
Aceclofenac may decrease the excretion rate of Metformin which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Metformin which could result in a higher serum level.
Acetazolamide
The risk or severity of lactic acidosis can be increased when Acetazolamide is combined with Metformin.
Acetohexamide
The risk or severity of hypoglycemia can be increased when Metformin is combined with Acetohexamide.
Acetyl sulfisoxazole
The therapeutic efficacy of Metformin can be increased when used in combination with Acetyl sulfisoxazole.
Acetyldigoxin
The serum concentration of Acetyldigoxin can be increased when it is combined with Metformin.
Acetylsalicylic acid
The risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Metformin.
Aclidinium
Metformin may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Acrivastine
Metformin may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Acyclovir
Acyclovir may decrease the excretion rate of Metformin which could result in a higher serum level.
Adefovir
Adefovir may decrease the excretion rate of Metformin which could result in a higher serum level.
Adefovir dipivoxil
Adefovir dipivoxil may decrease the excretion rate of Metformin which could result in a higher serum level.
Agmatine
The serum concentration of Agmatine can be increased when it is combined with Metformin.
25 References
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  8. 8 . Lucis OJ: The status of metformin in Canada. Can Med Assoc J. 1983 Jan 1;128(1):24-6.PubMed: 6847752
  9. 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. 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
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  12. 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. 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
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