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 [19]. 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 perip... 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 increa... 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

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
    Vitamin B12 Deficiency US
  • Kind: experimental
    • Percent: 7
  • 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
    Lactic Acidosis US
  • Kind: experimental
    • Percent: 0.03
  • Post Marketing
    Lactic Acidosis US
  • Kind: experimental
    • Percent: 0.000047
  • Post Marketing
    Mixed hepatocellular liver injury US
    Post Marketing
    Hepatocellular liver injury US
    Post Marketing
    Cholestatic liver injury US
    Post Marketing
    Hypoglycemia US
    Varying Reports

    Contraindications

    • Route:
      • Oral
    • Hypersensitivity:
      • true
    • Regions: US
    • Regions: Canada
    • Patient Conditions:
        • Name: Shock
        • Drugbank Id: DBCOND0020137
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions Associated With:
        • Name: Pregnancy
        • Drugbank Id: DBCOND0018394
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Dehydration
        • Drugbank Id: DBCOND0003946
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Stress conditions
        • Drugbank Id: DBCOND0108211
    • Patient Conditions Associated With:
        • Name: Surgery
        • Drugbank Id: DBCOND0020344
        • Name: Traumas
        • Drugbank Id: DBCOND0024565
        • Name: Infection
        • Drugbank Id: DBCOND0014227
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Excessive Alcohol Consumption
        • Drugbank Id: DBCOND0061174
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Lactic Acidosis
        • Drugbank Id: DBCOND0028962
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Hypoxemic state
        • Drugbank Id: DBCOND0124547
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Cardiorespiratory insufficiency caused by Heart Failure
        • Drugbank Id: DBCOND0124545
        • Combination Of:
          • Caused By:
              • Name: Heart Failure
              • Drugbank Id: DBCOND0027920
          • Included Conditions:
              • Name: Cardiorespiratory insufficiency
              • Drugbank Id: DBCOND0124546
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Cardiovascular collapse
        • Drugbank Id: DBCOND0095129
    • With Drugs Coadmin:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Renal Insuffiency
        • Drugbank Id: DBCOND0070847
    • With Drugs Coadmin:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Hepatic Insufficiency
        • Drugbank Id: DBCOND0031307
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe hepatic dysfunction
        • Drugbank Id: DBCOND0098613
        • Modification Of:
          • Base:
            • Name: Hepatic dysfunction
            • Drugbank Id: DBCOND0094733
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Serum creatinine above upper limit for age range
        • Drugbank Id: DBCOND0124544
    • Regions: Canada
    • Patient Conditions:
        • Name: Impaired kidney function
        • Drugbank Id: DBCOND0098871
    • Regions: Canada
    • Patient Conditions:
        • Name: Kidney function unknown
        • Drugbank Id: DBCOND0124543
    • Regions: US
    • Patient Conditions:
        • Name: Impaired kidney function
        • Drugbank Id: DBCOND0098871
    • With Drugs:
        • Name: Empagliflozin
        • Drugbank Id: DB09038
    • 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: 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. Food reduces irritation.