What is metformin? How does it work (mechanism of action)?
Metformin is an oral medication that lowers blood glucose (sugar) by influencing the body's sensitivity to insulin and is used for treating type 2 diabetes. Insulin is a hormone produced by the pancreas that controls glucose levels in blood by reducing the amount of glucose made by the liver and by increasing the removal of glucose from the blood by muscle and fat tissues. As a result, insulin causes blood glucose levels fall. Diabetes caused by a decrease in production of insulin that causes increased production of glucose by the liver, and reduced uptake (and effects) of insulin on fat and muscle tissues. Metformin acts by increasing the sensitivity of liver, muscle, fat, and other tissues to the uptake and effects of insulin. These actions lower the level of sugar in the blood.
Unlike glucose-lowering drugs of the sulfonylurea class, for example glyburide (Micronase, DiaBeta) or glipizide (Glucotrol), metformin does not increase the concentration of insulin in the blood and, therefore, does not cause excessively low blood glucose levels (hypoglycemia) when used alone. In scientific studies, metformin reduced the complications of diabetes such as heart disease, blindness, and kidney disease
The FDA aproved metformin in December 1994.
What are the uses for metformin?
- Metformin is used for treating type 2 diabetes in adults and children. It may be used alone or in combination with other diabetic medications.
- Metformin also has been used to prevent the development of diabetes in people who are at risk.
- Treatment of polycystic ovaries
- Weight gain due to medications used for treating psychoses.
What are the side effects of metformin?
The most common side effects with metformin are
These symptoms occur in one out of every three patients. These side effects may be severe enough to cause therapy to be discontinued in one out of every 20 patients. These side effects are related to the dose of the medication and may decrease if the dose is reduced.
Metformin may also cause:
- weakness or lack of energy
- respiratory tract infections,
- low levels of vitamin B-12,
- low blood glucose (hyperglycemia)
- constipation,
- indigestion, muscle pain,
- heartburn, and
- chills.
A serious but rare side effect of metformin is lactic acidosis. Lactic acidosis occurs in one out of every 30,000 patients and is fatal in 50% of cases. The symptoms of lactic acidosis are
- weakness,
- trouble breathing,
- abnormal heartbeats,
- unusual muscle pain,
- stomach discomfort,
- light-headedness, and
- feeling cold.
Patients at risk for lactic acidosis include those with reduced function of the
- kidneys or liver,
- congestive heart failure,
- severe acute illnesses, and
- dehydration.
What is the dosage for metformin?
- For treating type 2 diabetes in adults, metformin (immediate release) usually is begun at a dose of 500 mg twice a day or 850 mg once daily. The dose is gradually increased by 500 mg weekly or 850 mg every two weeks as tolerated and based on the response of the levels of glucose in the blood. The maximum daily dose is 2550 mg given in three divided doses.
- If extended tablets are used, the starting dose is 500 mg or 1000 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg except for Fortamet (2500 mg of Fortamet, once daily or in two divided doses). Glumetza tablets (500 -1000mg formulations are given once daily (either 1000 to 2000mg). Fortamet and Glumetza are modified release formulations of metformin. Metformin should be taken with meals.
- For pediatric patients 10-16 years of age, the starting dose is 500 mg twice a day. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg in divided doses.
- Children older than 17 years of age may receive 500 mg of extended release tablets daily up to a maximum dose of 2000 mg daily. Extended release tablets are not approved for children younger than 17 years of age.
- Metformin-containing drugs may be safely used in patients with mild to moderate renal impairment. Renal function should be assessed before starting treatment and at least yearly.
- Metformin should not be used by patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 and starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
- Metformin should be stopped at the time of or before administering iodinated contrast in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Kidney function should be evaluated 48 hours after receiving contrast and metformin may be restarted if kidney function is stable.
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Which drugs or supplements interact with metformin?
- Cimetidine (Tagamet), by decreasing the elimination of metformin from the body, can increase the amount of metformin in the blood by 40%. This may increase the frequency of side effects from metformin.
- Ioversol (Optiray) and other iodinated contrast media may reduce kidney function, which reduces elimination of metformin, leading to increased concentrations of metformin in the blood. Metformin should be stopped 48 hours before and after use of contrast media.
- Thiazide diuretics, steroids, estrogens, and oral contraceptives may increase blood glucose and reduce the effect of metformin. When these drugs are stopped, patients should be closely observed for signs of low blood glucose.
- Alcohol consumption increases the effect of metformin on lactate production, increasing the risk of lactic acidosis.
Is metformin safe to take if I’m pregnant or breastfeeding?
- There are no adequate studies in pregnant women. Most experts agree that insulin is the best treatment for pregnant women with diabetes.
- Metformin is excreted into breast milk and can therefore be transferred to the nursing infant. Nursing mothers should not use metformin.
What else should I know about metformin?
- Metformin is available as
- Tablets: 500, 850, and 1000 mg
- Tablets (extended release): 500, 750, and 1000 mg.
- Solution: 100 mg/ ml
- Metformin should be stored at room temperature between 20 C to 25 C (68 F to 77 F).
- Metormin is available in generic versions of immediate release and extended release formulations.
- You need a prescription from your doctor to obtain metformin.
- Brand names available for metformin in the US include:
- Glucophage
- Glucophage XR
- Glumetza
- Fortamet
- Riomet