With popular drugs like Ozempic and Mounjaro making headlines for managing blood sugar, it’s easy to forget that some drugs have been helping type 2 diabetes patients for decades. Metformin is a popular one. But while this drug has been around for more than 60 years, scientists are discovering what it does to the brain.
New research published in journal Advances in science identifies a brain pathway through which metformin appears to work (along with the impact it has on other areas of the body). It is generally accepted that metformin lowers blood sugar by reducing the amount of glucose the liver releases, but this study found that much of this glucose regulation appears to take place in the brain.
Meet the experts: Christoph Buettner, MD, Ph.D., chief of the division of endocrinology at Rutgers Robert Wood Johnson Medical School; Kelly Johnson-Arbor, MD, toxicologist at MedStar Health; Jamie K. Alan, Ph.D., Associate Professor of Pharmacology and Toxicology at Michigan State University
In a previous mouse study, the same research team discovered a protein in the brain called Rap1 that influenced how glucose is broken down in the body. During that study, the researchers found that metformin traveled to an area of the brain called the ventromedial hypothalamus, where it essentially shut down Rap1.
The researchers then bred mice that lacked Rap1 and found that metformin had no impact on blood sugar management, even though other drugs did. Overall, the findings suggest that metformin has a large impact on the brain.
But why does this matter? Here’s what doctors want you to know.
What is metformin?
Metformin is an oral drug in a class of drugs called biguanides that is commonly used to treat type 2 diabetes, according to the US National Library of Medicine. The medicine is designed to help control the amount of glucose (or sugar) in the blood. “Metformin has been used for decades to treat diabetes, although there has been extensive research into its use in other conditions such as cancer and PCOS,” says Jamie K. Alan, Ph.D., associate professor of pharmacology and toxicology at Michigan State University.
Metformin specifically lowers the amount of glucose you absorb from food as well as the amount of glucose your liver makes, according to Alan. At the same time, the drug increases the body’s response to insulin, a hormone that controls the amount of glucose in the blood.
“There are probably more complex mechanisms at play,” says Alan.
Metformin is also being explored for other health conditions. “Because metformin can pass through the bloodstream and into the brain, scientists have also studied whether it can be an effective treatment for depression and neurological disorders,” says Kelly Johnson-Arbor, MD, toxicologist at MedStar Health.
Why does this matter?
Even though metformin has been widely used for decades, the details of how it works have not been fully discovered. “Amazingly, even though metformin is a drug that has been used for more than six decades in the US, we still don’t fully understand how it works,” says Christoph Buettner, MD, Ph.D., chief of endocrinology at Rutgers Robert Wood Johnson Medical School. “It’s the most prescribed diabetes drug in the world.”
These findings suggest it could have an impact on the brain, liver and gut. “It’s valuable to learn how this works in the brain,” says Alan. “There is so much we don’t know about satiety and the central mechanisms behind appetite and blood sugar control.”
The findings “change the way we think about metformin,” says Dr. Buettner. “It supports the important role the brain plays in glucose metabolism,” he continues. “It may also explain why metformin causes modest weight loss, changes in appetite and hunger, and possible effects on brain aging or cognition, because these are effects on the brain.”
Metformin is also “extremely affordable,” says Alan. “It’s oral, so no injections are needed,” she adds. (By comparison, Ozempic and Mounjaro are injectable drugs.) As a result, finding new ways to use or similar treatments would be a big win for the diabetes community and beyond, she says.
These discoveries could lead to new and better treatments for a number of diseases, according to Dr. Johnson-Arbor. “By studying the effects of metformin outside the liver, scientists may be able to find new applications for this decades-old drug, such as new treatments for diabetes, neurological disorders and heart disease,” she says.
what is happening now
These are new findings, so more research is needed. However, the study’s research team also shared in a press release that they plan to dig deeper into how metformin affects the brain, including in humans.
However, experts say this is just the beginning. “Research is a long way from the clinic, but it’s important,” says Alan.
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