Metformin is an antidiabetic agent that belongs to a class of drugs called biguanides. The U.S. Food and Drug Administration (FDA) has approved metformin for use in treating type 2 diabetes, which occurs when glucose (blood sugar) builds up in the blood due to the body’s inability to effectively use insulin (a hormone that regulates glucose). Researchers are also studying metformin as a possible treatment for symptoms associated with polycystic ovarian syndrome (PCOS). Some physicians prescribe metformin to treat irregular ovulation for women with PCOS.

PCOS is a disorder of the endocrine system in which a woman's ovaries produce excessive amounts of androgens (male hormones such as testosterone). Among other symptoms, PCOS causes irregular menstrual cycles and raises the risk of heart disease. Clinical trials have found that metformin:

• Reduces androgen levels. High levels of male hormones significantly contribute to PCOS.
  
  
• Improves ovulation. Metformin allows women to resume regular menstrual cycles and can increase fertility in some women.
  
  
• Controls hirsutism when prescribed at higher doses. Hirsutism is excessive hair growth throughout the face and body. It is a symptom commonly associated with PCOS.
  
  
• Helps reduce the incidence of PCOS-associated obesity. It can also lead to better glucose regulation through its effects on insulin resistance. 

To date, the FDA has not specifically approved metformin as a treatment for PCOS. However, clinical trials are under way that may eventually result in the FDA approving metformin for PCOS therapy.

Metformin is an antidiabetic agent used to lower glucose (blood sugar) levels. Traditionally, it has been used to treat people with type 2 diabetes, which occurs when glucose accumulates in the blood due to the body’s inability to effectively use insulin (a hormone that regulates glucose). Research is under way to determine the effect of metformin in treating symptoms related to polycystic ovarian syndrome (PCOS). This is a type of endocrine system disorder in which the ovaries produce excessive amounts of androgens (male hormones such as testosterone). Some patients with PCOS are also insulin resistant.

Metformin belongs to a class of drugs called biguanides. These drugs prevent the liver from producing too much glucose, and reduce the amount of glucose from dietary sources. They also increase the sensitivity of muscle tissue to insulin, which allows for better absorption of glucose. Biguanides slow the absorption of glucose from food digested in the small intestine.

Metformin is the only biguanide approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes. However, clinical trials are testing the use of metformin in treating PCOS. “Off-label” use of metformin is currently prescribed by some physicians for PCOS patients. Off-label use allows physicians to prescribe FDA-approved drugs for patients who may benefit from their use, even though the drug has not been specifically approved for treating their condition.

Among other symptoms, PCOS causes irregular menstrual cycles and raises the risk of heart disease. Clinical trials have found that among women with PCOS, metformin:

• Reduces androgen levels. High levels of male hormones are a major contributor to PCOS.
  
  
• Reduces insulin resistance. High insulin levels may contribute to high androgen levels and irregular ovulation in women with PCOS.
  
  
• Improves ovulation. Metformin helps women resume their  regular menstrual cycles. Research indicates that the drug improves ovulation in normal-weight and overweight patients and increases fertility in some women.
  
  
• Controls hirsutism when prescribed at higher doses. Hirsutism is excessive hair growth throughout the face and body. It is a symptom commonly associated with PCOS because of the high male hormone levels.
  
  
• Helps reduce the incidence of PCOS-associated obesity.

Researchers believe that regular use of metformin may ultimately help reduce cardiovascular disease complications that stem from PCOS. Metformin may be a particularly good treatment option for women diagnosed with both PCOS and type 2 diabetes. However, to date, the FDA has not specifically approved metformin for treating PCOS. Metformin may help increase fertility among some women with PCOS. However, recent studies show that although metformin treats other symptoms of PCOS well, other drugs, such as the fertility drug clomiphene, work better for women who are trying to get pregnant.

Metformin is sold in various formulations and under several brand names, such as:

People with kidney disease (nephropathy) should not use biguanides such as metformin. These patients are at high risk of developing a buildup of lactic acid in the blood (lactic acidosis). This is the most serious side effect associated with metformin, and is potentially life-threatening.

A physician should test the kidney function of all candidates for metformin therapy. This can be done using a blood test called the serum creatinine, or a urine test.

Symptoms of lactic acidosis include weakness, fatigue and unusual muscle pain or stomach discomfort.

Liver disease, heart failure and alcohol abuse all can trigger lactic acidosis. Patients with a history of those conditions may not be good candidates for biguanide therapy. Alcohol affects how metformin is metabolized, so even patients who do not drink regularly should do so in moderation. Patients who drink to excess, even sporadic episodes of binge drinking, should alert their physicians before beginning therapy with metformin. Dehydration also raises the risk of lactic acidosis, so patients should talk to their physician about ways to keep hydrated in all circumstances.

Patients who are having surgery or medical tests that use dye should inform their physician of their use of metformin. The dyes can impair kidney function, causing the drug to build up in the blood. Patients may be advised to suspend their use of these medications for a period of time.

Other conditions that may affect use of metformin include:

• Severe injury, burns or infection
  
  
• Severe diarrhea or vomiting
  
  
• Female hormone changes that occur during puberty, menstruation or pregnancy
  
  
• Ketones (produced when fat is burned for energy instead of glucose) in the urine or blood
  
  
• Abnormal functioning of adrenal, pituitary or thyroid gland
  
  
• Severe intestinal problems, including slow stomach emptying
  
  
• Major surgery
  
  
• Poor food absorption and undernourishment
  
  
• Conditions that cause low glucose (blood sugar) or rapid glucose changes
  
  
• Heart or blood vessel disorders
  
  
• Liver disease
  
  
• Severe mental stress

Although metformin has not been associated with birth defects, the drug is rarely prescribed to women who are pregnant. Women should inform their physician if they are pregnant or planning to become pregnant before beginning treatment with metformin. Women who are breastfeeding should also notify their physician prior to beginning metformin treatment. Studies have not determined if the drug passes into a woman’s breast milk.

Side effects associated with biguanides, such as metformin, often can be greatly reduced by taking the medication with food. Side effects may include:

• Stomach problems, including:
  
  
• Nausea and vomiting
• Diarrhea
• Abdominal bloating or gas
  
  
• Breathing difficulties
  
  
• Buildup of lactic acid in the blood (lactic acidosis)
  
  
• Resumption of ovulation in premenopausal women who are not ovulating. This might necessitate the use of contraception if pregnancy is not desirable.

Some patients may find that use of biguanides prevents the body from properly absorbing vitamin B12. This can increase the risk of B12 deficiency, which can cause nerve damage and other problems. A physician may suggest vitamin supplements as a way to restore proper levels of vitamin B12.

Biguanides can cause a significant increase in ovulation (up to eight times), which is one reason why they are used to treat polycystic ovarian syndrome. Women taking biguanides should consult with a physician, preferably an obstetrician-gynecologist (ObGyn), about the medication’s effect on fertility.   

Metformin usually interacts well with other medications. However, patients should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications.

Patients who take metformin must be careful to limit their consumption of alcohol, as they can become sick if they consume more than two to four drinks a week.

Other medications that may interact poorly with metformin include:

• Calcium blocking agents. These increase blood and oxygen supply to the heart and include:
  
  

  Amlodipine Bepridil Diltiazem  Felodipine Flunarizine

  Isradipine Nicardipine Nifedipine Nimodipine Verapamil

  
  
• Amiloride, furosemide and triamterene (reduce swelling and fluid retention)
  
  
• Cimetidine and ranitidine (help treat ulcers and other stomach conditions)
  
  
• Dioxin, procainamide and quinidine (heart medications)
  
  
• Morphine (painkiller)
  
  
• Quinine (treats malaria)
  
  
• Trimethoprim (treats urinary tract infections)
  
  
• Vancomycin (antibiotic)
  
  
• Warfarin (anticoagulant)

Metformin is not known to be associated with birth defects or other problems in humans. However, the drug is not often prescribed to women who are pregnant. Women should tell their physician if they are pregnant or considering becoming pregnant before beginning treatment with metformin.

It is not known if metformin passes into breast milk. Women who are breastfeeding should consult with their physician before taking metformin.