6 Reasons Why Metformin Might Not Be Safe For PCOS

By Clare Goodwin

Last updated: September 3, 2020

Have you been prescribed metformin for PCOS and are wondering what the side affects are? Metformin is often described as a ‘safe’ drug, but read on to find out why this might not be the case.

The first thing I asked my GP when I received my diagnosis was what I could take to ‘fix’ it. She gently explained that there was no pill or surgery that could cure my condition. However, there was a drug that could help with the elevated insulin levels caused by it: metformin. She claimed it was a safe drug with no major side effects that would help with insulin resistance and weight loss.

At first, I thought metformin was a wonder drug. I lost about 5kg in 4 months, more than I had ever been able to lose previously. I was ecstatic.

Metformin side effects

I had a quick look online to see whether there were any side effects. I found that diarrhea, loose stools, fatigue, and muscle soreness were commonly experienced. But I thought that it was small price to pay for finally being able to lose some weight.

However, when I investigated further I found that that there are some much more sinister side effects of metformin that aren’t so widely publicised. These include:

  • Depleting our bodies of essential nutrients.
  • Increasing the risk of having a baby with a neural tube defect by up to 9 times.
  • Reducing energy levels by almost 50%.
  • Killing beneficial gut bacteria.

This article is not intended to be a case against metformin for PCOS. There is no doubt that metformin helps to reduce weight, lowers blood glucose levels, and promotes ovulation. My concern is the lack of studies about the safety of long-term use of metformin for PCOS, especially in utero.

Drugs can help with the associated symptoms of a disease, but they cannot fix the root cause of it. Metformin is a drug with a band-aid approach. This means that whilst it helps to fix some parts of the body, it causes damage to others. Current research shows that some natural remedies are just as effective at improving insulin resistance. It’s therefore time to question the use of metformin for PCOS.

What is Metformin?

Metformin is a drug that is said to make our cells more sensitive to insulin. It’s therefore commonly used to treat insulin resistance – something which affects 70-80% of women with PCOS. If you’re not sure if you have insulin resistance then you can find a full explanation of insulin resistance here

Insulin is a storage hormone.When we eat, our body detects a rise in blood sugar (glucose). Our body doesn’t like our blood sugar levels to be too high, as this can lead to damage of the cells. These cells include our brain, liver, pancreas, heart, and eye cells. The body therefore stores any excess glucose in muscle and liver cells for later use.

Insulin is an incredibly important hormone that allows the efficient storage of glucose. It does this by ‘unlocking’ cells and allowing glucose to go into them. Without insulin our cells would starve. This is why people with Type 1 diabetics  (where the body doesn’t produce any insulin) need to inject insulin to survive.

Insulin is excreted by the pancreas. There, it binds to specialised receptors on cells to unlock them, similar to the way a key opens a door. Insulin resistance occurs when the cells fail to respond to insulin correctly. The result of this is that the excess glucose cannot be stored efficiently. As a result, the pancreas tries to produce more insulin in order to it to have its proper effects. This continues until the pancreas can no longer produce sufficient insulin, causing blood sugar levels to rise.

How does Metformin work?

Metformin works by lowering the amount of glucose in the blood. It does this in three ways:

By preventing the liver from creating excess glucose

When there is too much glucose in the blood, the pancreas sends a message to the liver and tells it to stop producing more glucose. However, this is disrupted if you have insulin resistance. Instead, the liver continues to release more and more glucose, exacerbating the problem. Metformin helps by mimicking the messenger and acting directly on the liver to tell it to stop producing more glucose.

By increasing the sensitivity of muscle cells to insulin

This makes them more able to remove excess glucose from the blood.

By slowing the absorption of sugars from the intestines

This lowers overall blood sugar levels.

Metformin and weight loss

Our body doesn’t like sugar being in the blood for too long, as it starts to damage cells. Instead, the excess sugar is transported into the liver, where it is converted into fat and stored for later use. Metformin can help to control weight by preventing the excess glucose in the blood. Preventing excess glucose reduces fat storage in the liver. Despite this, metformin appears to be no more efficient than dieting or widely available natural treatments.

One study showed that metformin helped women to reduce their weight by 5-10 pounds over a 4-8 month period. However, a high protein diet and resistance training can produce the same amount of weight loss. It’s also worth noting that the high protein diet didn’t exclude any inflammatory foodsso it would be even more interesting to see the combined results of an anti inflammatory diet and resistance training.

The study above reflects my own personal experience of metformin and PCOS, and that which I’ve seen in many of my patients. Metformin appears to be very effective in reducing weight by about 5kg, but then seems to simply stop working.

Metformin and pregnancy

Our ovaries are very sensitive little things. In our evolutionary days, ovulation (and the ability to turn it on and off), was our only form of contraception. Our body didn’t want to risk bringing a baby into the world unless the environment was absolutely perfect for it. As a result, we developed the ability to shut down ovulation if the environmental conditions weren’t suitable.

One theory suggests that when the body detects high blood sugar then it perceives this as an unsuitable environment for pregnancy and subsequently shuts down ovulation. We would therefore expect that reducing blood glucose levels would improve ovulation rate.

Indeed, an analysis of 13 trials on metformin and PCOS concluded that metformin helped to improve ovulation rate. However, the researchers made an important note in their conclusion.

“No data is available regarding the safety of metformin in long term use in young women and only limited data on it’s safety in early pregnancy.”

This is an incredibly important point to note. While metformin for PCOS may help with conception rate, is there are greater price that we, and the unborn foetus, pay for that?

Some herbs and supplements can be just as beneficial as metformin for PCOS.

The unknown Metformin side effects

We know that high blood sugar and diabetes is dangerous. This is why metformin, a drug which prevents them, is never really critically evaluated.

Like all drugs, metformin doesn’t treat the root cause of the problem. It cannot help with all of the things that cause high blood sugar and insulin resistance. Instead it treats the symptoms caused by them, chemically covering up the protective mechanism of insulin resistance and overriding what is an important bodily process. What’s worse, however, is that by doing this metformin is also damaging the body in many other ways, including:

Metformin depletes the body of nutrients, leading to insulin resistance and weight gain

That’s right. Metformin can actually cause the problems that it’s supposed to treat. Metformin depletes the body of essential nutrients, such as vitamin B12 and folate.

Vitamin B12 is involved in a huge number of important bodily processes.  This includes hormone production, DNA and RNA synthesis, and nerve conduction. Needless to say, B12 deficiency definitely isn’t something you want.

I know what you’re thinking. Okay, that might not be good, but surely it’s a small price to pay if I want lose weight and get pregnant?

Wrong. So very wrong.

If you have PCOS and insulin resistance, then you already have much lower levels of vitamin B12 than you should. Studies have also shown that the lower your vitamin B12 and folate levels are, the more likely you are to have  insulin resistance and gain weight. In fact, treatment with both of these can help to improve insulin resistance and reduce inflammation. It’s therefore likely that the deficiency is partly to blame for causing the insulin resistance in the first place.

30% of people who take metformin for PCOS are vitamin B12 deficient. If you have PCOS and insulin resistance caused by low levels of B12, you don’t want to take a drug which could lower those levels even more.

Metformin may predispose your unborn child to neural tube defects

Metformin and PCOS can cause a vitamin B12 deficiency which is associated with insulin resistance. However, B12 deficiency can also cause an increased risk of neural tube defects in unborn children. This is important for all women, but especially those who are trying to get pregnant.

One study found that mothers with a vitamin B12 deficiency were up to nine times more likely to have a baby with neural tube defect, compared to those who did not have a deficiency.

Risk of Neural Tube Defects per 1000 Births According to Maternal B12 Status

Source: Molloy, A et al (2009) Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification. Pediatrics;123;917-923

Given this information, it would be expected that vitamin B12 levels are checked in all women who are prescribed metformin for PCOS, especially if trying to concieve. However, from my experience this is rarely happening.

I recently conducted an online survey and found that almost 75% of women who had been prescribed metformin for PCOS and had neither had their B12 levels checked or been advised that they may need a B12 supplement. Although this may not be scientifically accurate, it certainly replicates what I’m seeing with my patient base.

Number or women that have been prescribed Metformin for PCOS and also had B12 levels checked and/or a supplement recommended

If you are trying to conceive and taking metformin for PCOS, then it’s essential to make sure you are getting your vitamin B12 and folate levels checked. I’d also recommend working with a practitioner to ensure your levels are optimum.

Metformin during pregnancy leads to heavier mothers and babies

It’s been shown that metformin can cross the placental barrier and therefore potentially impact the foetus. However, what’s also concerning is that there have been few studies that have looked at potential postnatal effects on the baby.

Although there is no conclusive evidence, some studies have indicated that metformin may cause metabolic changes in babies born to mothers who have taken the drug during pregnancy. These metabolic changes could predispose the child to complications later in life.

For example, one study found that in women who took metformin during pregnancy, both mother and baby were heavier one year postpartumcompared to women who were given a placebo.

In addition, a study on mice found that baby mice exposed to metformin in the womb suffered from a damaged metabolism later in life and were more likely to become obese.

Let’s think about that evidence for a moment. Metformin is a drug that we know disrupts the normal communication in the body, can cross the placental barrier, and may potentially lead to metabolic disruption in babies. I’m not sure how that passed ethics approval.

Metformin can reduce your energy by up to 48%

Every cell in the body contains mitochondria. Mitochondria can be compared to tiny powerhouses, providing energy to cells so that they can carry out all their functions.

Studies have shown that metformin depletes the mitochondria’s ability to produce energy, meaning that you are effectively operating on half the energy that you should have.

This means that when you’re taking metformin for PCOS,  then the cells in all of your essential organs, including your brain and heart, your GI tract and muscle cells are only working at half capacity.

It is no wonder women taking metformin for PCOS feel so fatigued all the time.

Metformin kills your gut bacteria

Gut bacteria is essential for immune function and proper weight regulation. Read any forum about metformin and you’ll find loads of stories from women who are having to base their everyday lives around where the nearest toilet just incase they have an ‘incident’.

However, what most people don’t realise is that this side effect of metformin is much worse than suffering from loose stools. The reason that metformin has this effect is because it’s actually an antibiotic which seriously affects the microbiome (community of bacteria) living in the intestine.

There are 100 trillion bacteria living inside our intestines, and studies have shown that they are responsible for 70% of our immune system functioning. We also know that these bacteria directly control the calories that we extract from food and therefore aid weight regulation.

It’s no wonder then that if these bacteria are disrupted then weight loss gets even harder.

Metformin stops exercise for insulin resistance working

In my article, What’s the Best Exercise for PCOS Weight Loss” I explained how research shows that resistance exercise is the best kind for women with PCOS because it’s the most effective for weight loss. This is because resistance exercise makes our muscles more sensitive to insulin

But metformin stops this from happening.  One study divided people with insulin resistance into three groups: one group took metformin, one group did resistance exercise, and the final group was took metformin and also did exercise. Participants in the metformin group showed reduced blood insulin levels. Participants in the exercise group also showed reduced blood insulin levels, in addition to reduced blood glucose levels. However, in the metformin and exercise group, participants actually had increased insulin and blood glucose levels.

Effect of metformin, exercise and both on blood glucose and insulin levels

Metformin for PCOS and exercise

Natural Metformin alternatives

There are many natural alternatives, which have robust research, that have been found to be just as effective as metformin at reducing insulin resistance and promoting weight loss.

One example is a berberine, a herb extract. One study which compared berberine and metformin found that berberine improved all markers of insulin sensitivitymore so than metformin.

Effect of Berberine vs Metformin on Insulin Resistance

Metformin for PCOS and natural alternatives

Unfortunately, as they do not receive training about them in medical school, doctors generally have limited knowledge about herbs and supplements. Therefore, they they won’t be able to advise you on what’s suitable for you and your condition.

But don’t worry, because I’ve compiled a cheat sheet for you, which contains details of all of the natural remedies which have been scientifically proven to be as effective as metformin for PCOS and helping with weight loss and insulin sensitivity.  Included is information about herbs, such as berberine mentioned above, vitamins, diet, exercise and alternative treatments, all of which can help you with the weight loss and insulin sensitivity complications associated with PCOS.