Examples

Generic Name	Brand Name
metformin hydrochloride	Glucophage, Glucophage XR

How It Works

Metformin decreases the level of androgens produced by the ovaries and adrenal glands. It also helps the body use insulin and may reduce the risk of diabetes.

Metformin lowers blood sugar levels by:

• Decreasing the amount of sugar produced by the liver.
• Increasing the amount of sugar absorbed by muscle cells and decreasing the body's resistance to insulin (insulin resistance).

When blood sugar is lower, less insulin is needed, so the body makes less insulin. And when insulin is lower, the body produces a lower level of androgens.

Why It Is Used

Metformin is a diabetes medicine sometimes used for lowering insulin and blood sugar levels in women with polycystic ovary syndrome (PCOS). This helps regulate menstrual cycles, start ovulation, and lower the risk of miscarriage in women with PCOS. Long-term use also lowers diabetes and heart disease risk related to high insulin levels. ¹

Metformin: ¹

• Does not cause the pancreas to make more insulin. When taken alone, it will not cause low blood sugar (hypoglycemia).
• Lowers fat (lipid and triglyceride) levels in the blood.
• Reduces abnormal clotting factors and markers of inflammation that can lead to hardening of the arteries (atherosclerosis).
• Decreases the level of androgens.

Metformin can be used to treat women with PCOS to reduce insulin levels and promote normal ovarian function. Metformin is best used in addition to eating a healthy diet, losing weight, and exercising regularly.

How Well It Works

Metformin lowers insulin, androgen, and cholesterol levels. It also improves metabolism in women who are insulin-resistant.

• Metformin may be useful in restoring regular menstrual cycles and starting ovulation in about 45% of women with PCOS. ²
• In general, oral fertility medicines are the first choice of treatment for infertility. ³
• Clomiphene (Clomid) and metformin may be more effective when they are taken together, but more research is needed to confirm if this is true.
• Some studies show that taking metformin has helped with in vitro fertilization (IVF), but other research did not support this.
• Metformin may lower the risk of miscarriage or gestational diabetes in women with PCOS, but this has not yet been confirmed by research. Metformin is probably safe to take while you are pregnant, but as metformin is only FDA-approved for the treatment of diabetes, you should talk with your doctor about the use of this medicine for reducing your risk for miscarriage or treating PCOS symptoms.

Side Effects

The most common side effects of metformin are:

• Nausea.
• Loss of appetite.
• Diarrhea.
• Increased abdominal gas.
• A metallic taste.

These side effects occur 20% to 30% of the time. Side effects usually decrease over time. The dosage of metformin is usually increased gradually to prevent these possible side effects. ⁴

Blood levels of vitamin B12 can decrease in women who take this medicine, but the lower level usually does not cause health problems. Doctors do recommend that women on metformin take a daily multiple vitamin supplement.

A rare side effect of taking metformin is a condition called lactic acidosis. This happens when metformin builds up in the blood instead of being removed by the kidneys. If not treated, this acid buildup can lead to coma and death.

Metformin should not be used by women who:

• Are dehydrated from not eating or drinking, or from having a fever.
• Are about to have a surgical procedure or an X-ray with contrast dye.
• Have kidney or liver problems.
• Drink excessive amounts of alcohol.

The use of metformin during pregnancy is not well researched. So if you are pregnant or are trying to get pregnant, be sure to talk with your doctor about what is best for you.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

You may need to stop taking metformin temporarily before major surgery or other medical procedures, such as X-rays that use contrast dyes. Talk to your doctor about this before your surgery or procedure.

The effect of metformin may be increased if you also take cimetidine (Tagamet). Before taking metformin, talk with your doctor about any other medicines you are taking.

Metformin is safe to use in teenage girls with PCOS. Some experts suggest starting long-term metformin therapy when PCOS is first diagnosed, with the goal of lowering the risks of diabetes, infertility, and heart disease. But the safety of long-term treatment is not yet known. ⁵

Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.

Citations

1. Ehrmann DA (2005). Polycystic ovary syndrome. New England Journal of Medicine, 352(12): 1223–1236.

2. Lord JM, et al. (2003). Metformin in polycystic ovary syndrome: Systematic review and meta-analysis. BMJ, 327(7421): 951-953.

3. Legro RS, et al. (2007). Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 356(6): 551–566.

4. Barbieri RL (2007). Polycystic ovary syndrome. In DC Dale, DD Federman, eds., ACP Medicine, section 16, chap. 5. New York: WebMD.

5. Speroff L, Fritz MA (2005). Anovulation and the polycystic ovary. Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 465–498. Lippincott Williams and Wilkins.