Alternatives to glucophage for treating insulin resistance in PCOS

For women with polycystic ovary syndrome – PCOS, insulin resistance is a common finding. In addition, many of these women do not respond to Clomid (Clomiphene Serophene) (Clomid resistance). For these reasons, many women are now treated with a diabetes medication known as glucophage (metformin) which works, in part, to reduce insulin resistance and improves the chances for ovulating spontaneously or with Clomid. However, many women will have side effects from glucophage such as bloating, cramping, diarrhea, flatulence and nausea. The most serious complication of glucophage is lactic acidosis which is a rare but potentially life threatening condition.

Sitagliptin (Januvia)

Incretins are naturally occurring hormones secreted from the intestines in response to food intake. In the pancreas, incretin hormones act to increase insulin secretion in response to rising sugar levels in the blood. This helps to ensure an appropriate insulin response following ingestion of a meal.

Sitagliptin prolongs the action of incretin hormones by prohibiting their degradation through inhibition of the dipeptidyl peptidase-4 enzyme (DPP4).

A 12 week study of obese women with PCOS who were unable to tolerate metformin were treated with sitagliptin. Sitagliptin was found to improve insulin resistance. another study found that the chance for ovulation was similar to metformin. sitagliptin, however, was tolerated much better than metformin was.

Sitagliptin has been rated by the FDA as belonging to pregnancy category B. Reproduction studies have been performed in rats and rabbits. Doses of sitagliptin up to 12 time the maximum recommended human dose did not impair fertility or harm the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Sitagliptin administered to pregnant female rats and rabbits from gestation day 6 to 20 (organogenesis) did not produce birth defects at approximately 30- and 20-times the maximum recommended human dose. Higher doses increased the incidence of rib malformations in offspring at approximately 100 times human exposure at the MRHD.

Byetta (Exenatide for injection)

Byetta belongs to a class of medications known as incretin mimetics. The incretin hormone which scientists have studied the most is called glucagon-like peptide-1 (GLP-1). Byetta works by mimicking the effects of GLP-1. Studies show it increases insulin sensitivity.

Byetta is approved by the FDA for the treatment of diabetes – not PCOS yet. Two advantages of Byetta that have been shown in clinical studies include better control of blood sugar levels in diabetics and weight loss. Since Byetta improves insulin resistance, some scientists feel that PCOS patients may benefit from taking Byetta.

In a study of 60 overweight women with PCOS, Byetta improved the likelihood of women having regular menstrual cycles. The combination of Byetta with metformin was found to be better than either metformin or Byetta alone. Byetta alone showed improvement in several parameters such as weight, BMI, insulin resistance and androgen levels. Byetta in combination with metformin improved these parameters to a greater extent then Byetta alone.

It is clear, therefore, that Byetta exerts a positive impact on PCOS patients and that combining Byetta with metformin works better than either medication alone.

Byetta has been rated by the FDA as belonging to pregnancy category C. Byetta has been shown to cause reduced fetal and neonatal growth and skeletal effects in mice.  Byetta has also been shown to cause skeletal effects in rabbits. There are no adequate and well-controlled studies in pregnant women. Byetta should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The most common adverse events associated with Byetta were nausea, vomiting, diarrhea, feeling jittery, dizziness, headache, and dyspepsia. In October of 2007, the FDA reported that it had received 30 reports of patients taking Byetta developing a serious condition known as pancreatitis. Five patients developed serious complications from the pancreatitis such as kidney failure. Although most patients improved after they stopped taking Byetta, eight out of the thirty patients did not improve.

Since those initial reports, there have been several studies trying to determine if there is a relationship between Byetta and pancreatitis. The results have been mixed, some studies showed an increased risk, some did not. Complicating the matter is the fact that type 2 diabetics have a higher rate of pancreatitis even without the use of Byetta. As of late 2011, there were no reports of PCOS patients taking Byetta developing pancreatitis.

At this time, Byetta cannot be recommended as a first-line treatment for PCOS. It may be considered as an alternative, however, with proper counseling.

Glycosidase Inhibitors for PCOS Treatment

Precose (Acarbose)

50-100 mg and are taken with meals

Miglitol (Glyset)

50-100 mg and are taken with meals

Acarbose is another medication used to treat diabetes. Acarbose is an alpha-Glycosidase inhibitor. It works by reducing the absorption of monosaccharides (simple sugars) through intestines and minimize the increase in blood sugar and insulin seen after meals. Serious side-effects of acarbose are rare and although it shares many of the gastrointestinal side effects as glucophage (abdominal distension, diarrhea and flatulence), lactic acidosis is not a problem with this drug. side effects may lessen over time.

Some studies have demonstrated that these medications are capable of lowering the androgen levels in women with PCOS.

In a recent study, researchers looked at 30 women with polycystic ovary syndrome – PCOS who did not previously respond to Clomid . The women were divided into two groups. One group received acarbose and Clomid. The other group received glucophage and clomid.

By the end of three months, the women taking acarbose lost more weight than the glucophage group. Both groups showed a similar improvement in the number of women who ovulated. There were 15 women in each in group and they were studies for three months so there was a possibility of 45 ovulatory cycles (15 x 3). The acarbose group had 20 ovulations and the glucophage group had 24 ovulations. The incidence of side effects was the same in both groups and there were no serious adverse effects in either group.

In summary, it seems that acarbose could provide a reasonable alternative to glucophage for treating insulin resistance in polycystic ovary syndrome – PCOS patients, though the expected benefits are minimal. This was a small study so there isn’t nearly as much data showing a positive effect as exists for glucophage at the moment. Acarbose did not have a better ovulation rate than glucophage so the main benefit comes down to a lower risk of lactic acidosis which is a very rare complication anyway.

I would think of acarbose as a second line drug for the time being. If first line drugs like glucophage were not tolerated or ineffective than trying something like acarbose might be reasonable.

Chromium treatment for PCOS

Chromium is a mineral required in small quantities by the body. It enables insulin to function normally and helps the body process (metabolize) carbohydrates and fats. Good sources of chromium include carrots, potatoes, broccoli, whole-grain products, and molasses. Picolinate, a by-product of the amino acid tryptophan, is paired with chromium in supplements because it is claimed to help the body absorb chromium more efficiently. Chromium deficiency is very rare in developed countries. Nonetheless, it has become a popular supplement.  Chromium picolinate has been suggested to promote weight loss, build muscle, reduce body fat, and enhance the function of insulin. It may lower levels of cholesterol and triglycerides.

Chromium picolinate is of possible interest in the treatment of PCOS patients due to its possible effects in improving insulin resistance. A few small studies have been performed in which women with PCOS were given chromium.

One such study, in women with polycystic ovary syndrome, found that chromium picolinate (200 μg/d) improved glucose tolerance compared with placebo but it did not improve ovulatory frequency or the abnormal hormonal parameters commonly found in women with PCOS. The authors of this study concluded that future studies in the polycystic ovary syndrome population should examine higher dosages or longer duration of treatment.

Another study examined the effects of chromium picolinate at a dose of 1000 ug per day. PCOS patients were given chromium but were instructed not to change their diet or exercise level. These PCOS patients experienced a  38% mean improvement in a measure of insulin resistance. These authors concluded that chromium picolinate, an over-the-counter dietary product, may be useful as an insulin sensitizer in the treatment of polycystic ovary syndrome.

Exercise and PCOS

Exercise may be the single most important lifestyle factor for both preventing and reversing insulin resistance. Exercise training results in a preferential loss of abdominal body fat and reverses the loss of muscle mass associated with insulin resistance, providing the single-most important intervention for changes in body composition.

Exercise improves insulin sensitivity in skeletal muscles and fat tissue, reducing both fasting blood sugar and insulin levels. Findings demonstrate that consistent exercise training, even without accompanying improvements in body composition, improve peripheral insulin activity in subjects with impaired glucose tolerance.

Even an exercise routine as simple as incorporating brisk walking four times weekly dramatically improves endurance fitness, decreases body fat stores, tends to reduce food consumption, and decreases insulin resistance.

To date, only a few controlled studies have examined the direct effects of physical exercise in PCOS women. In the first study, a 6-month exercise program significantly decreased plasma total homocysteine concentrations and waist-to-hip ratio, but had no effect on fasting insulin or androgen levels in young overweight and obese women with PCOS.

More recently, a 2005 study showed that insulin resistance was improved by up to 25% in sedentary women with PCOS and insulin resistance following a 5-month moderate-intensity exercise program without weight loss. In 2007, investigators determined that any improvements seen with exercise in PCOS patients were lost within 12 weeks if they stopped their exercise program.

Green Teas for PCOS

Many varieties of green tea have been created in China and other countries. these teas can differ substantially due to variable growing conditions, processing and harvesting time. Although many health benefits are supposed to result from drinking green teas, few if any of these claims have been proven in rigorously performed studies.

Herbal Drugs and Chemicals

Unfortunately, the internet has resulted in a huge increase in the use of herbal drugs and elixirs. In addition to being exempt from U.S. Food and Drug oversight, there is little evidence to support the use of these powerful chemical compounds. There are reported cases of adverse complications occurring in women taking these things to try to promote their fertility.

Cinnamon for PCOS

Cinnamon is a spice that comes from the bark of a small evergreen tree native to Sri Lanka and South India. The bark is widely used as a spice due to its distinct odor. In India it is also known as “Daalchini”.

Cinnamon is prepared by roughly pounding the bark, soaking it in sea-water, and then quickly distilling the result. Cinnamon contains a large amount of active chemicals including cinnamic aldehyde, ethyl cinnamate, eugenol, cinnamaldehyde, beta-caryophyllene, linalool and methyl chavicol.

Like other herbal remedies, there are many varieties of cinnamon which have distinct chemical components and may differ from each other substantially. It is therefore difficult to perform accurate scientific comparisons and draw valid conclusions.

In the summer of 2007, a very small pilot study was performed to determine whether cinnamon had any beneficial effects on women with PCOS. Fifteen women with polycystic ovary syndrome were randomized to daily oral cinnamon and placebo for 8 weeks. The results indicated a reduction in insulin resistance in the cinnamon group but not in the placebo group. Because the number of women studied was so small, a larger trial is needed to confirm the findings of this pilot study.

Vitex for PCOS

Vitex agnus-castus  (commonly called just Vitex, but also called Chaste Tree, Chasteberry, or Monk’s Pepper — is a plant which grows in the Mediterranean region. The leaves, stem, flowers and ripening seeds, have been used for medicinal purposes.

The berries have been used as an herbal drug for both the male and female reproductive systems. The leaves are believed to have the same effect but to a lesser degree. This plant is commonly called monk’s pepper because it was originally used as anti-libido medicine by monks to aid their attempts to remain celibate. It is believed to decrease sexual interest, hence the name chaste tree.

There is little if any clinical evidence of a benefit of Vitex for infertility or women with PCOS. Like other herbal drugs, many varieties of the plant are grown in various areas. The chemical composition is quite complex and varied from variety to variety.

One study has found that treatment with one variety of Chinese Vitex caused a slight reduction of a pituitary hormone known as prolactin in mice. There are no studies in human beings. There are no studies which have looked at the effects of Vitex in women with PCOS.