Metformin – The Complete Guide for Non-Diabetics

by

Should Healthy People Take Metformin?

Background

  • Drug or Supplement: DRUG
  • Natural or synthetic: NATURAL
    • metformin is extracted from the herb Galega officinalis (French lilac, also known as goat’s rue or Italian fitch
  • Years since Discovery: 99 (1922)
  • Safe for Humans: YES
    • Based on the fact that it is taken by more than one hundred million people worldwide and has been for decades. I would hope we would know if there were serious, detrimental effects by now.
  • Research Demonstrating Effectiveness in Humans: TRUE
  • Discoverer: UNKNOWN
  • Typical Dosage: 500mg b.i.d
  • Human Half Life: 4-8.7 hours

Metformin is the fourth most commonly prescribed drug in the United States. 88 million people in the United States alone take it. It is the most commonly prescribed treatment for Type II diabetes.

French Lilac. One of the plants metformin comes from

Mechanism of Action

Metformin works by:

  1. Decreasing glucose production by the liver
  2. Increasing the insulin sensitivity of body tissues

Editors note: we have noticed immediate and sustained (over a period of hours) reductions in our blood glucose after taking 500mg of metformin. So we are surprised that is has a low risk of causing low blood sugar.

Where Can You Buy Metformin?

Since in many countries it is a drug, you need to visit a doctor to receive a prescription.

Here is a list of countries for which you do and don’t need a prescription to get metformin. Perhaps on your next trip to one of these countries you can stock up for a while.

What Conditions Does It Treat?

  1. Type II Diabetes
  2. It is also taken to treat polycystic ovary syndrome
  3. It appears to reduce the rate of various cancers in quite a few studies

Who Takes It?

And what do those prominent in the anti-aging community say about metformin?

  1. Nir Barzilai – Says that there are “lots of animals, and if you give them metformin they live longer”
    – Nir Barzilai has specialized in researching metformin, ostensibly because he believes in it. There is a plethora or videos on YouTube where he discusses metformin. He has also thoroughly researched the Ashkenazi Jewish community centenarians in the New York City area. His book is excellent and I recommend it.
    – I don’t assume that Nir Barzilai takes metformin, though I do not actually recall him saying whether or not he personally takes it.

What prominent scientists DO take metformin?

  1. David Sinclair

What prominent longevity scientists DON’T take metformin?

  1. Peter Attia
  2. Matt Kaeberlein (he says doesn’t take it in the YouTube video below)
  3. Charles Brenner

Everyone mentioned above has an MD or PhD. I don’t want anyone getting offended.

Matt Kaeberlein thinks that “[metformin] might help” and that it “probably won’t hurt” (see below YouTube video for a link to exactly where he says this).

If you have updates about what any of the above mentioned scientists and doctors have said about metformin, please let me know!

Watch more of what Kaeberlein thinks here (he mentions that “metformin blunts the effects of exercise“):

Here is what I could find about what Dr. Brenner thinks about metformin:

Who May Want to Take Metformin?

Metformin simulates caloric restriction and exercise. While “cardio” exercise reduces future diabetes more than metformin does, again it may be a good option for those that refuse to exercise or can’t exercise.

So people that can’t or won’t exercise are candidates for taking metformin. Also those who have a family history of Type II diabetes may want to consider taking metformin.

Who Shouldn’t Take It

  1. Those who have recently resistance trained or are very serious about resistance training. See this article.
Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial
Because metformin reduces inflammation, we hypothesized that it would augment the muscle response to progressive resistance exercise training (PRT) in healthy older participants. Following 14 weeks o…
Wiley Online LibraryR. Grace Walton

Common Side Effects

The most common side effects are gastrointestinal in nature. Meaning it upsets your stomach. Personally for me, and this is verging on TMI, it doesn’t give me diarrhea but sort of just makes me need to use the bathroom more. This does go away after a few weeks for most people.

Nausea, vomiting, stomach upset, diarrhea, weakness, or a metallic taste in the mouth may occur.

Long term use (multiple years; the study used 3.2 years) can cause Vitamin B12 deficiency Actual study

How Much Does it Cost?

Since Metformin is a generic drug it is very affordable. It costs from $26-$52 per month in the U.K, depending on if you take 500mg or 1000mg per day. Generic versions are made in countries all around the world. We believe that in India, for instance, the cost would be closer to $10-$15 per month based on mail orders we have seen.

Most Important Research Paper

This is the most cited research papers about metformin:

  1. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes [link] The Lancet, Volume 352, Issue 9131, 1998
    Even though metformin was discovered in 1922, it wasn’t used, in the “West” at least, until the 1990s. This study appears to be one of the first that “investigated whether intensive glucose control with metformin has any specific advantage or disadvantage.”
    The paper found that “Median glycated haemoglobin (HbA1c) was 7·4%in the metformin group compared with 8·0% in the conventional group. Patients allocated metformin, compared with the conventional group, had risk reductions of 32% (95% CI 13–47, p=0·002) for any diabetes-related endpoint, 42%”

Should Healthy People Take Metformin?

The science is mixed about this. We certainly do not know if metformin reduces all-cause mortality. We won’t know that for at least decades. Not like that trial is being done anyways. Or will be done.

There is very little research in healthy people, since it is prescribed for Type II diabetes. It is fairly definitive that it blunts the effects of cardiovascular exercise.

  1. New York Times Article about metformin blunting the benefits of cardio vascular exercise
  2. CAMERA study: Metformin for non-diabetic patients with coronary heart disease: a randomised controlled trial
    – n = 173
    – mean age: 63
    – Results: “Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose”
    – Takeaway: “Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins”
    – However:
    – My thoughts: It’s surprising that A1c declined but fasting glucose didn’t. I would have thought there would have been a strong correlation between these two variables. But metformin did not positively impact common CVD markers for those that were high risk.
    – Everyone in this trial were taking statins
    – I reviewed the differences between the placebo and control groups they were fairly similar with no glaring differences.
    – There were almost three times as many people excluded from the primary outcome analysis though in the metformin group. (11 metformin excluded vs 4 placebo group excluded). This is a large difference, when the primary outcome analysis groups are only 75 and 83 respective. The reasons stated for the difference are (metformin group on left and placebo right):

– So I wonder about this big difference. Is it possible that a few of the metformin group had other positive health tests and decided “this trial isn’t for me; I’m healthy now?”. Possible. We don’t know. Unfortunately this adds to the uncertainty about “metformin for non-diabetics”. Although this trial was 100% statin takers, which also isn’t “metformin for healthy non-diabetics”.
– So besides not meeting the primary endpoint, this study did measure some non-CVD metrics that could be interesting for us. Let’s look at those.
– (metformin group is on the left in the following images)
– metformin significantly reduced all measures of adiposity (body weight [by over 3kg], body fat, body mass index, and waist circumference) compared with placebo,

We will continue to update this section as more research becomes available.

Does metformin prevent cancer?

It sure seems to.

There have been quite a few large studies showing that those who take metformin have reduced rates of cancer.

I recommend reading this overview of publications about the reduced risk of cancer of those who were taking metformin.

  1. In this metaanalysis, which included 47 independent studies with 65,540 cancer cases in patients with diabetes they showed that overall cancer incidence was reduced by 31%. Cancer mortality was reduced by 34%. When they controlled for BMI, the rate of cancer was still reduced by 18%. They concluded that the magnitude of reduction was modest and did not affect all populations equally. This is the forest plot for this meta-analysis. The horizontal lines to the left of the vertical line show the reduction of each study. I wonder what happened in the second study that showed an increase in cancer rates

Do Diabetics Who Take Metformin Live Longer than Non-Diabetics?

There was a famous observational study done in England which was published in 2013. This study is quoted over and over. Perhaps it should be; perhaps it shouldn’t be. In the study, they observed that aged (the entire study covered 60-75 year olds) diabetics who took metformin did live 15% longer than non-diabetics who were not taking metformin in a 2.5 year observation period. Almost all of the effects were seen in the 71-75 year old age group. The two 61-65 and 65-70 old groups showed only a slight advantage for metformin. See our article here about this study and our thoughts about it.