Metformin (Glucophage)

Metformin is a drug that increases the body’s sensitivity to insulin. It also decreases glucose (sugar) production by the liver and decreases intestinal absorption of glucose. Metformin, however, does not cause hypoglycemia (low blood sugar). It is known that some women with polycystic ovarian syndrome (PCOS) have insulin resistance. Although not diabetic, they must secrete larger amounts of insulin to keep their blood sugar in the normal range. It is thought that high insulin levels may contribute to the ovulatory dysfunction that is seen with PCOS. Therefore, improvement in insulin sensitivity in PCOS patients may help ovulation. When given to women with PCOS, metformin has been shown to be associated with a decrease in male hormone levels, improvement in menstrual patterns and a better response to ovulation induction with fertility drugs.

Most studies have not looked at pregnancy as the endpoint, so the true benefit, if any, of metformin on pregnancy rates remains to be determined. The main reason to give metformin is to facilitate ovulation, either spontaneous, or induced. Some women who are not trying to get pregnant may be placed on metformin. In these women metformin may cause their menstrual periods to become more regular and may decrease their risk of developing diabetes. The safety of metformin use in pregnancy has not been established in humans. Metformin is a “Class B” drug, which means that animal studies have not demonstrated any harmful effects, but definitive human studies are lacking. Continuation of metformin during pregnancy may have some beneficial effects including a decrease in the miscarriage rate and a decrease in the development of gestational diabetes.

The side effects of metformin are primarily gastrointestinal and are most common during the first few weeks of therapy. These include diarrhea, nausea, vomiting, abdominal bloating, flatulence (gas), and decreased appetite. These symptoms generally improve with time. An unpleasant or metallic taste is sometimes noted, but this also usually goes away. Metformin has been associated with a serious and sometimes fatal condition called “lactic acidosis”. This has been reported to occur in about 1 in 33,000 patients who take metformin. These patients have usually had preexisting kidney disease. Symptoms of lactic acidosis include feeling very tired and weak, unusual muscle pain, trouble breathing, feeling cold, dizzy or lightheaded, or suddenly developing a slow or irregular heartbeat. Should you develop any of these symptoms you should report them immediately to your doctor. The risk of lactic acidosis is increased if you have kidney or liver disease, drink alcohol heavily (including binge drinking) or become severely dehydrated. If you are to have an x-ray procedure using iodine containing contrast, such as an IVP or HSG, you should stop taking metformin 2 days prior to the procedure and not restart it until 2 days after the procedure. You should not drink excessive amounts of alcohol while taking metformin. You should notify your doctor if you are diagnosed with any type of kidney or liver disease while taking metformin.

One of the beneficial side effects of metformin is weight loss. Many women with PCOS are overweight and the benefits of weight loss have been clearly established. Therefore if you take metformin you might expect some weight loss. However, you should also work at improving your dietary habits and increasing your physical activity to further enhance weight loss.

Metformin has been approved by the United States Food and Drug Administration (FDA) for the treatment of non-insulin dependent diabetes mellitus. Its use as an adjuvant to ovulation induction and fertility treatment has not been approved by the FDA, but numerous research studies have shown that it may be beneficial.