Understanding Metformin

There are many reasons why a woman may not ovulate regularly. It appears that some women are resistant to the hormone insulin. Insulin is normally thought of as the hormone produced by the pancreas that helps regulate blood sugar. While this is true, insulin also has many other effects in the body. The ovary has receptors for insulin and thus insulin is capable of modifying hormone production from the ovaries.

The are several conditions that may result in a woman becoming resistant to the effects of insulin. Among these are  PCOS – Polycystic Ovary Syndrome – genetics and obesity. When insulin resistance occurs, the body needs a higher level of insulin to accomplish the same tasks. High insulin levels are frequently seen in this condition.

If insulin resistance is the cause for a woman’s anovulation (not ovulating) then it stands to reason that improving the insulin resistance or lowering the insulin levels may be successful at causing ovulation to return.

In fact some studies in overweight women with insulin resistance demonstrated that Metformin (Glucophage) was successful in getting ovulation to occur without any other additional medications. It also seemed to improve the response to a fertility medication called clomiphene citrate.

Results of the World’s Largest Metformin Study

Recently, a study was published comparing metformin to clomid in patients with PCOS. This study was conducted on over 600 patients and involved several academic centers. There were three groups of patients that were compared. Group 1 took metformin alone. Group 2 too clomid alone. Group 3 took a combination of metformin and clomid.

The outcome being measured in this study was the live birth rate. Patients were treated for 6 months or until an ongoing pregnancy occurred. The results were somewhat surprising. The total cumulative live birth rate in the metformin group after 6 months was only 7%. The clomid group had a live birth rate of about 25%. The live birth rate in the combination group was similar to the rate with clomid alone.

The results of this study indicate that while it is possible to ovulate and achieve pregnancies with metformin – this treatment is not nearly as efficient as clomid. Furthermore, combining clomid and metformin did not do any better than clomid alone. The main advantage of metformin therefore, is that the rate of multiple pregnancies was lower than in the clomid groups.

A secondary outcome looked at in this study was whether metformin was able to lower the miscarriage rate in women with PCOS. In fact, the results were just the opposite. The metformin groups had a higher rate of miscarriage although, when analyzed statistically, the results could have been due to chance.

Metformin (Glucophage) Instructions

Glucophage comes as either a short acting or extended release (Glucophage XR). I like to use the XR for a few reasons:

  • The tablets can all be taken together at the same time. It is not necessary to spread the dose out as was done with the short acting variety
  • The side effects seem to occur less frequently

Glucophage XR comes as 500 mg tablets. Most women will start with the 500 mg tablets. The starting dose is one tablet a day for one week. If this dose has been tolerated, then two tablets a day are taken during the second week. Finally, three tablets a day are taken during third week and continues thereafter. Some women will tolerate the medicine well and can increase their dose more quickly. Others may need to go more slowly.

Metformin also comes in a liquid preparation known as Riomet. There is also a long acting formulation that comes in a higher dose. Fortamet come in 1000 mg tablets. If a PCOS patient had demonstrated that she can tolerate the higher dose of metformin, switching to Fortamet can make pill taking a little easier since only two pills are required to reach the desired 2000 mg dose.

Metformin Side Effects

Gastrointestinal disturbance: Approximately 1/3 of the people who take glucophage will experience one or more of the following symptoms: nausea, diarrhea, vomiting bloating, or flatulence. Starting on a lower dose (1 tab / day) may reduce the likelihood of this problem. Taking glucophage with meals also may help. Symptoms do resolve with continued treatment.

Lactic acidosis: This is a rare but serious metabolic condition that results from accumulation of lactate in the blood. It can be seen in persons with diabetes, kidney problems and other problems. Glucophage may cause Lactic acidosis in 3 in 100,000 patients taking Glucophage over the course of a year. Lactic acidosis can be fatal when serious.

The symptoms of lactic acidosis are often subtle and non-specific. They include malaise, muscle aches (myalgia), difficulty breathing, increasing sleepiness (somnolence), and non-specific abdominal distress. IF YOU EXPERIENCE THESE SYMPTOMS, CONTACT THE OFFICE IMMEDIATELY.

Because of the risk of lactic acidosis, you should not take Glucophage if:

1. You have chronic kidney or liver problems
2. You drink alcohol excessively
3. You are scheduled to undergo a hysterosalpingogram or have surgery
4. You are pregnant

Metformin effects on pregnancy

A small series suggested that using metformin during pregnancy may have a benefit in terms of reducing the risk of miscarriage or gestational diabetes. Metformin is considered pregnancy category B. Animal studies in rats and rabbits at very high doses did not result in a higher than expected incidence of birth defects. There are no good, well-controlled trial in women. One study suggested that the use of metformin in pregnancy resulted in a higher incidence of some pregnancy complications. It is recommended that Metformin be stopped immediately upon the diagnosis of pregnancy. However, studies are currently ongoing to try to determine the safety and effectiveness of metformin in pregnancy.

A recent study has found pre-eclampsia, a complication of pregnancy involving high blood pressure, was over four times higher when metformin was used to treat gestational diabetes. You should read more about metformin risks here.