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What is Metformin? A Summary of N,N-dimethylbiguanide

We take a look at the drug metformin, which is popular with biohackers.

Metformin bottleMetformin bottle
 

We take a look at this diabetic drug that some researchers think may slow down aging.

What is metformin?

Metformin is a prescription drug and is available as a tablet or an oral solution. It is a commonly used first-line medication for the treatment of type 2 diabetes and is also used in the treatment of polycystic ovary syndrome.

You can find metformin tablets in two forms: immediate-release and extended-release. The immediate release tablet goes by the brand name Glucophage, and the extended release goes by Glucophage XR, Glumetza, and Fortamet.

Both types of tablet are sold as generic drugs, as the patent on metformin expired back in 2001. Generic drugs typically cost significantly less than the brand name versions, though in some circumstances, they may not be available in all of the strengths  that brand name suppliers offer.

Metformin is in the biguanide class of drugs, a group of drugs that work in a similar way. It was originally discovered in 1922, but it did not receive approval for another fifty years or more [1]. The French physician Jean Sterne initiated the first study in humans in the 1950s; it was registered as a medicine in France in 1957, but it was not approved until 1995 in the United States [2].

The World Health Organization lists metformin on its model list of essential medicines, a list of the most effective and safe medicines that are critical in a health system. To that end, metformin is believed to be one of the most widely used drugs used for the treatment of diabetes.

How does metformin work?

It works by decreasing glucose production in the liver, reducing the amount of glucose your body absorbs, and boosts the effect of insulin on your body. Insulin is a hormone that assists your body in removing excessive sugar from your bloodstream, and this helps to reduce your blood sugar levels, a cause of diabetes.

In this manner, metformin helps people with type 1 diabetes to manage their condition by keeping their high blood sugar under control.

Metformin and anti-aging

There is a constant process of balance happening in our cells between anabolic processes that produce energy from nutrients and catabolic processes that consume that energy. This balancing act becomes critical when there is a scarcity of nutrients to keep our cells powered and functioning.

Famine is an example of when this balance becomes vitally important to keep someone alive. When such conditions are experienced our cells switch to a pro-survival state and prioritize survival and energy conservation instead of growth. By entering this state our cells have a better chance to survive and help us to remain alive. Without a doubt our ancient ancestors who often experienced periods of starvation and famines would have benefited from this.

Metformin seems to trigger the same pro-survival state in our cells by reducing the activity of our mitochondria, the powerhouses of our cells. This causes the mitochondria to slow down the pace at which they convert nutrients into a universal cellular energy known as adenosine triphosphate (ATP).

The reduction in ATP triggers an enzyme known as AMPK which detects low energy levels. This then activates various pro-survival mechanisms including autophagy to conserve energy and keep the cells alive.

Metformin may also support longevity by lowering both insulin resistance and blood sugar levels. By improving the way the body manages insulin it may even help non-diabetics to live a longer and healthier life.

Some researchers, such as Dr. Nir Barzilai, believe that metformin may prove useful as a way to slow down aging and is leading a clinical trial called TAME to find out if it can. We talked to him about his interest in metformin in the “We Can Live Healthier for Longer” interview.

Potential health benefits

There is some evidence that metformin may help to prevent the cardiovascular and cancerous complications of diabetes [3-4]. Metformin is also not associated with weight gain, so it is ideal for diabetics who suffer from weight control issues, which are common in diabetes.

Generally speaking, metformin is well tolerated and appears to have protective effects on the vascular system [5], though some common side effects can include diarrhoea, nausea and abdominal pain. There is risk of high blood lactic acid if taken inappropriately and in overly large doses [6]. It should not be used by people with significant liver damage or kidney problems.

Metformin is of interest to people working in the field of rejuvenation biotechnology, and mouse studies show that it increases lifespan and healthspan [7]. There is also some data that suggests that type 2 diabetics that take metformin may also live longer than non-diabetics [8].

Metformin side effects

Taking metformin can cause mild side effects, including diarrhea, nausea, stomach pain, heartburn, and gas. More serious potential side effects include lactic acidosis and hypoglycemia (low blood sugar). You should call your doctor if you experience any side effects while taking metformin.

However, metformin has a number of known interactions with other drugs, including diabetes drugs such as insulin and glyburide, along with blood pressure management drugs such as furosemide and hydrochlorothiazide.

Cholesterol-modifying drugs, such as NAD+ precursor niacin, are worth noting, as this is a popular supplement in the life extension community and can make metformin less effective in lowering blood sugar levels.

Using metformin with the glaucoma drugs acetazolamide, brinzolamide, dorzolamide, and methazolamide may increase your risk of lactic acidosis. Metformin has known interactions with topiramate, a drug used to treat nerve pain and seizures, and may raise your risk of lactic acidosis. Phenytoin, which is used to treat seizures, can make metformin less effective in lowering your blood sugar. Cimetidine, which is used to treat heartburn and other stomach problems, can interact with metformin and increase your risk of lactic acidosis.

Some hormone drugs may also make metformin less effective in lowering blood sugar. Corticosteroids like budesonide, fluticasone, prednisone, and betamethasone have potential interactions. Estrogens such as estradiol, conjugated estrogens (Premarin), and birth control pills or patches can also interact. Isoniazid, an anti-tuberculosis drug, can also make metformin less effective in lowering blood sugar.

Thyroid drugs may make metformin less effective in lowering your blood sugar too. These include levothyroxine, liothyronine, and liotrix.

Lactic acidosis is an uncommon but very serious side effect of metformin. This is when lactic acid builds up in the bloodstream and is a medical emergency that requires treatment in the hospital. It is fatal in about half of people who develop it.

Disclaimer

This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.

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Literature

[1] Fischer, J., & Ganellin, C. R. (Eds.). (2010). Analogue-based drug discovery II. John Wiley & Sons.

[2] Stargrove, M. B., Treasure, J., & McKee, D. L. (2008). Herb, nutrient, and drug interactions: clinical implications and therapeutic strategies. Elsevier Health Sciences.

[3] Malek, M., Aghili, R., Emami, Z., & Khamseh, M. E. (2013). Risk of cancer in diabetes: the effect of metformin. ISRN endocrinology, 2013.

[4] Griffin, S. J., Leaver, J. K., & Irving, G. J. (2017). Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia, 60(9), 1620-1629.

[5] Triggle, C. R., & Ding, H. (2017). Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium. Acta Physiologica, 219(1), 138-151.

[6] Lipska, K. J., Bailey, C. J., & Inzucchi, S. E. (2011). Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes care, 34(6), 1431-1437.

[7] Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., … & Schwab, M. (2013). Metformin improves healthspan and lifespan in mice. Nature communications, 4, 2192.

[8] Bannister, C. 1., Holden, S. E., Jenkins‐Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G., … & Currie, C. J. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non‐diabetic controls. Diabetes, Obesity and Metabolism, 16(11), 1165-1173.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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