With blood sugar management like Ozempic and Mounjaro making headlines, it’s easy to forget that some drugs have been helping patients with type 2 diabetes for decades. Metformin is a popular one. But while the drug has been around for more than 60 years, scientists have discovered what it does to the brain.
The new research is published in the journal Science advances Identifies the brain pathway that metformin appears to work on (along with effects on other areas of the body). It’s generally accepted that metformin lowers blood sugar by reducing how much glucose the liver puts out, but this study shows that glucose regulation is mostly in the brain.
Meet with the experts: Christoph Buettner, MD, Ph.D., head of the department of endocrinology at Rutgers Robert Wood Johnson Medical School; Kelly Johnson-Arbor, MD, a toxicologist at MedStar Health; Jamie K. Allen, Ph.D., Associate Professor of Pharmacology and Toxicology at Michigan State University
In a previous mouse study, the same research team found a protein called Rap1 in the brain, which affected how glucose is broken down in the body. During that study, the researchers discovered that metformin traveled to an area of the brain called the ventromedial hypothalamus, where it essentially shut down Rap1.
The researchers then bred mice lacking Rap1 and found that metformin had no effect on their blood sugar management, even though other drugs did. Overall, the findings suggest that metformin has major effects on the brain.
But why is it different? Here’s what doctors want you to know.
What is metformin?
According to the US National Library of Medicine, metformin is an oral medication in a class of drugs called biguanides that is commonly used to treat type 2 diabetes. Medicines are designed to help control the amount of glucose (or sugar) in the blood. Jamie K., associate professor of pharmacology and toxicology at Michigan State University. “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 Allen, PhD.
Metformin specifically reduces the amount of glucose you take in from food, as well as the amount of glucose made by the liver per liter. At the same time, the drug increases the body’s response to insulin, the hormone that controls blood glucose levels.
“There are probably more complex mechanisms at play as well,” Allen says.
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, a toxicologist at MedStar Health.
Why is it different?
Although metformin has been widely used for decades, the details of how it works have not been fully figured out. “Surprisingly, even though metformin has been used in the US for more than six decades, we still don’t fully understand how it works,” says Christoph Buettner, MD, PhD, chief of endocrinology at Rutgers Robert Wood Johnson Medical School. “It is the most prescribed diabetes drug in the world.”
These findings suggest that it may affect the brain, liver, and gut. “It’s important to know how it works in the brain,” says Allen. “We don’t know much about satiety and the central mechanisms behind appetite and blood sugar control.”
The findings “change the way we think about metformin,” Dr. Buettner says. “This supports the important role the brain plays in glucose metabolism,” he continues. “This may also explain why metformin causes modest weight loss, changes in hunger and appetite, and possible effects on brain aging or cognition, these are brain effects.”
Metformin is also “very affordable,” Allen says. “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 it or similar treatments would be a big win for the diabetes community and beyond, she says.
These findings could potentially lead to new and better treatments for various diseases, Dr. According to Johnson-Arbor. “By studying the effects of metformin outside the liver, scientists may be able to discover new applications for this decades-old drug, such as new treatments for diabetes, neurological disorders and heart disease,” she says.
What happens 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 take a deeper dive into how metformin affects the brain by looking at humans.
Still, experts say this is just the beginning. “Research is a long way from the clinic, but it’s important,” Allan says.
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