How Does Metformin Work?

What is metformin?

Metformin (chemical name: dimethylbiguanide) is a medication commonly used to treat type 2 diabetes.

Essentially, it works by lowering insulin resistance. It makes it easer for cells in the body to take up insulin and use insulin. This means that even if a person’s pancreas is only able to make a little bit of insulin, their cells can use that insulin more effectively.

Then, your pancreas does not have to work quite as hard.

Also, eat less carbohydrate, and your pancreas does not have to work so hard.

The name of metformin, dimethylbiguanide, breaks down as follows. “Di methyl” refers to two methyl groups (a grouping of one carbon and three hydrogen atoms: CH3) on the molecule. “Bi guanide” refers to a grouping of two guanide structures in the molecule.

Like many names of chemicals, “dimethylbiguanide” sounds complex at first, but is really just a list of the groups of atoms in the molecule it describes.

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Keep in mind that THE lifestyle factors to lower insulin resistance, are diet/nutrition, and exercise of any kind!

Physical activity that includes moderate intensity or high intensity builds muscle mass, increases strength, and makes your circulatory system more efficient. There are many benefits to building muscle mass. Muscle burns calories even at rest.

Aerobic exercise or “cardio” builds cardiovascular endurance.

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What does metformin do?

Normally in the body, the digestive system breaks down carbohydrates, and glucose enters the bloodstream from the gut.

Metformin helps with this glucose by helping it get into the cells in the rest of the body, especially skeletal muscle (the voluntary muscles that we are considering when we think about going to the gym).

Glucose ALSO enters the bloodstream from the liver. That’s right; your liver manufactures its own glucose in a process called gluconeogenesis. Metformin slows this process down, decreasing the amount of glucose that the liver adds.

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Side effects of metformin

All drugs have multiple effects. We call the ones we like, the intended effects. We call the ones we don’t like, side effects.

Side effects of metformin include stomach upset. Probably symptoms such as nausea or diarrhea are the most common side effects, but not very dangerous for most people.

Metformin can increase the risk of a metabolic illness called lactic acidosis, which is a serious condition when it occurs. Some patients are at more risk for this than others.

However, there are also “good” side effects and some off-label uses. Some studies have suggested benefits of metformin to the cardiovascular system and the kidneys.

Metformin does not tend to cause weight gain. This is notable since many diabetes medications, including insulin, stimulate the body to add fat.

Some patients benefit by decreased symptoms of PCOS (polycystic ovarian syndrome). PCOS causes infertility and higher risk for gestational diabetes.

Metformin is widely considered to have little to no risk of hypoglycemia. It is widely considered to have less risk for hypoglycemic episodes than other diabetes medications including insulin and sulfonylureas.

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Metformin discovered

The first precursor to metformin, guanidine, was recognized as lowering blood sugar as early as 1918. By the 1940s, guanide medications were used to treat diabetes. However, there were a lot of side effects. Since a lot of patients were dying from lactic acidosis, these drugs fell out of favor.

Metformin was first used to treat diabetes in 1957, by a French doctor named Jean Stern.

At least two other guanide type medications were experimented with and discarded by the 1970s due to side effects. Metformin has less side effects than other medications of this type.

Metformin was used for years in Europe before the U.S. approved its use for diabetes treatment in 1995.

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Sources

Bailey CJ. Metformin: historical overview. Diabetologia. 2017 Sep;60(9):1566-1576. doi: 10.1007/s00125-017-4318-z. Epub 2017 Aug 3. PMID: 28776081.

Buse JB, DeFronzo RA, Rosenstock J, Kim T, Burns C, Skare S, Baron A, Fineman M. The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies. Diabetes Care 2016;39(2):198–205. doi: https://doi.org/10.2337/DC15-0488. Epub 2015 Aug 18. Print 2016 Feb 1.

Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014 Jul;19(7):658-64. PMID: 25364368; PMCID: PMC4214027.

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