Metformin

Metformin is one of the oldest, most widely used, and least-expensive antidiabetic drugs for treatment of type 2 diabetes (T2DM). It is one of several orally-available medicines for this disease, but is very different structurally from the other compounds.

Other Names

Chemical structure of metformin hydrochloride. Source: NIH

Uses

Metformin is used to help control blood glucose levels in persons with type 2 diabetes by reducing glucose production in the liver and increasing sensitivity to existing insulin. It is not a replacement for injected insulin and is not used in treating type 1 diabetes. It is often used in combination with other medications as part of regimen that includes recommendations for weight loss and decreased caloric intake.

Metformin is also used in treating polycystic ovary syndrome.^[1]

How Metformin Is Taken

Metformin is provided as tablets to take by mouth; the tablets may contain metformin as the only active ingredient or may also contain other medicines. The regular tablet is usually taken with meals two or three times a day. The extended-release tablet is usually taken once daily with the evening meal. Tablets are usually taken at the same time each day and should be swallowed whole. The dose of metformin is adjusted gradually in response to how well it is tolerated and how well the patient's blood sugar levels respond to the drug.

How It Works

In contrast to some other medications, the precise (molecular) mechanism of metformin is not known. However, it is well-established that metformin acts as an insulin sensitizer in that it increases the blood glucose-lowering activity of insulin. The beneficial glycemic effects of metformin are mainly attributed to lowering the amount of glucose produced by the liver (hepatic gluconeogenesis), and increased peripheral tissue insulin sensitivity. Metformin probably works by interrupting mitochondrial oxidation in the liver and by correcting intracellular calcium abnormalities in tissues such as the liver, fat, and skeletal muscle.^[2]

How the body affects Metformin

Metformin is excreted unchanged in the urine. The body does not seem to modify metformin, as no metabolites have been identified in humans, and the drug is not excreted in the bile. After oral administration, about 90% of the absorbed drug is eliminated via the kidneys in the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the drug may enter and leave red blood cells.

Benefits

Blood glucose control; tendency to lose weight; improved lipid levels...

Side Effects

Metformin alone does not lead to low blood sugar levels; however, it is often taken in combination with other medications that can cause this. Symptoms of low blood sugar (hypoglycemia) include shakiness, dizziness or lightheadedness, sweating, nervousness or irritability, sudden changes in behavior or mood, headache, numbness or tingling around the mouth, weakness, pale skin, hunger, and clumsy or jerky movements.

Metformin itself may cause may cause side effects. In most patients, the effects are not troublesome enough to mandate discontinuation. Commonly-reported side effects of metformin include: diarrhea, bloating, stomach pain, gas, constipation, unpleasant metallic taste in mouth, heartburn, headache, sneezing, cough, runny nose, flushing of the skin, nail changes, and muscle pain.

Chest pain or rash are serious side effects that require immediate discontinuation of metformin and medical evaluation.

Risks and Precautions

Metformin carries a very small risk of causing lactic acidosis; the risk is about 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L), decreased blood pH, and electrolyte disturbances. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 µg/mL are generally found.^[3]

Interactions

History

Goat's rue provided starting material for the discovery of metformin. Source: Wikimedia Commons

Alternatives

Statistics

Research

Interesting Facts

• The relatively simple chemical structure of metformin contributes to its low cost, since the molecule can be made from even simpler starting materials in large quantities. A recent publication describes an improved (ecologically friendly, using only a few mg of reactants and a few drops of solvent) method for metformin synthesis that involves a 5-minute reaction in a microwave.^[6]

References

1. ↑ Moll E, van der Veen F, van Wely M. The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update. 2007 Nov-Dec;13(6):527-37. Abstract | Full Text | PDF
2. ↑ Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002 Jul 2;137(1):25-33. Abstract | PDF
3. ↑ Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med. 2003 Nov 24;163(21):2594-602. Abstract | Full Text | PDF
4. ↑ Hadden DR. Goat's rue - French lilac - Italian fitch - Spanish sainfoin: gallega officinalis and metformin: the Edinburgh connection. J R Coll Physicians Edinb. 2005 Oct;35(3):258-60. Abstract
5. ↑ http://www.fda.gov/bbs/topics/ANSWERS/ANS00627.html "FDA Approves New Diabetes Drug "
6. ↑ Shalmashi A. New Route to Metformin Hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) Synthesis. Molbank 2008, M564. Full Text

External links

• Metformin (in wikipedia)