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...
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Pharmacodynamic
**General effects**
Insulin is an important hormone that regulates blood glucose levels [19]. Type II diabetes is characte...
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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...
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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...
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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**...
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Adverse Effects
Effect | Regions | Age Groups | Incidences | Evidence Type |
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Diarrhea | US |
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Vomiting | US |
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Nausea | US |
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Flatulence | US |
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Diarrhea | US |
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Asthenia | US |
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Indigestion | US |
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Vitamin B12 Deficiency | US |
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Nausea | US |
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Vomiting | US |
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Abdominal Discomfort | US |
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Headache | US |
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Abnormal stools | US |
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Hypoglycemia | US |
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Myalgia | US |
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Lightheadedness | US |
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Dyspnea | US |
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Nail disorders | US |
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Rash | US |
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Increased sweating | US |
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Taste Disorders | US |
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Chest discomfort | US |
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Chills | US |
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Flu syndrome | US |
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Flushing | US |
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Palpitation | US |
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Myalgia | US |
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Hypoglycemia | US |
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Dyspnea | US |
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Light-headedness | US |
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Abnoraml stools | US |
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Chest discomfort | US |
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Chills | US |
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Flu-like Syndrome | US |
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Flushing | US |
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Nail disorder | US |
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Rash | US |
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Increased sweating | US |
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Taste Disorder | US |
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Palpitation | US |
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Lactic Acidosis | US |
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Lactic Acidosis | US |
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Mixed hepatocellular liver injury | US |
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Hepatocellular liver injury | US |
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Cholestatic liver injury | US |
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Hypoglycemia | US |
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Contraindications
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Food Interactions
Avoid alcohol.
Take with food. Food reduces irritation.