Metformin (dimethylbiguanide), a powerful antidiabetic agent, is an oral drug that is considered in most standard guidelines as the first-line treatment for Type 2 Diabetes. Since its introduction as a recognized medication in the 1950s, it has helped many people with Type 2 Diabetes and has been extensively prescribed by doctors worldwide. But what is the actual science behind this modern miracle?
Through the Looking Glass: Metformin's Mechanism of Action
In the world of pharmacology, metformin is placed under the biguanides medication class, with its active ingredient being guanidine. According to the American Diabetes Association, the drug traces its roots back to medieval Europe, when the Galega plant was used as a treatment for diabetes (and if you want to a few key definitions about Type 2 Diabetes, check out this article I wrote!).
On a molecular level, the complete mechanisms of this drug class are still not fully understood. Looking at it piece-by-piece, we can see that various studies have something to say about its effects.
Metformin is thought to act primarily on the liver by inhibiting the release of hepatic glucose. After ingesting metformin—usually in the form of a pill—it is slowly absorbed in the upper part of the small intestine and then transported to the liver. This is also the same reason why, aside from the gut, the hepatocytes (tiny cells making-up the liver) end up getting higher amounts of metformin compared to the blood.
Once it arrives in the hepatocytes, it acts through various signaling pathways to regulate gluconeogenesis, which is another term for glucose production in the liver.
One of the most important enzymes that metformin activates is AMPK, or AMP-activated protein kinase. AMPK is responsible for controlling the metabolism of glucose and fat in the liver. Simply put, it causes the liver to pump out less glucose into the bloodstream, thereby lowering blood sugar.
Two other ways in which metformin lowers blood sugar are 1) decreasing the absorption of glucose from the intestine and 2) increasing uptake of circulating glucose into the body's cells.
Metformin achieves its peak concentration within 4-8 hours after administration and it is often administered twice daily. Once ingested, metformin is primarily unchanged throughout the process and does not undergo metabolization, leaving it unbound and delivered all throughout the body until it gets excreted by the kidneys. It's recommended that people who take metformin also stick to a healthy lifestyle (diet & exercise)!
Here's further research to learn about Metformin:
Fast facts related to metformin treatment:
- According to "Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications" (2019), metformin has been found to increase glucose uptake in fat cells—a process that goes on with or without insulin. This was especially evident in people with obesity.
- Metformin can be used to enhance fertility among people with polycystic ovarian syndrome (PCOS).
- The use of metformin has increased among pregnant women. No evidence of adverse effects has been observed in multiple trials of metformin use in pregnancy. In spite of this, current recommendations still state that it should be discontinued upon the confirmation of pregnancy, as it has the ability to cross the placenta. Further studies are likely needed to change these recommendations.
- Metformin is present in breast milk in small amounts. Metformin may be used in breastfeeding women, but nursing mothers are advised to consult their doctors first before taking in any form of diabetes medication.
As with any treatment, there are necessary precautions that should be considered before metformin is prescribed. It is important to let your doctor know what kind of medications you are currently taking and what other conditions you are experiencing that may warrant additional tests. If you want to compare Metformin with other medications you're taking, check out Caretalk's treatment comparison tool.
Metformin has helped many people in the last few decades, improving the quality of life of those with Type 2 Diabetes worldwide. Medications are only one part of the management, together with proper diet and exercise. It is still important to actively do your part in your care, all while taking advantage of the marvels of modern medicine.