Metformin’s blood sugar control starts in the brain, not just the liver, study finds
For more than six decades, metformin has been one of the most trusted drugs for type 2 diabetes. Doctors have long believed it worked mainly in the liver and gut. But now, scientists have made a surprising discovery — metformin also acts on the brain.
A New Role for the Brain in Blood Sugar Control
Researchers at Baylor College of Medicine, along with international collaborators, found that metformin lowers blood sugar by targeting a brain protein called Rap1 in the hypothalamus — the part of the brain that helps control metabolism.
Dr. Makoto Fukuda, senior author of the study, explained:
“We’ve known that metformin reduces glucose production in the liver and interacts with the gut, but our findings show that the brain is also a key player in how this drug works.”
The Rap1 Connection
The team studied genetically engineered mice lacking Rap1 in a brain region called the ventromedial hypothalamus (VMH). When these mice were given metformin, their blood sugar levels did not drop — unlike normal mice. Interestingly, other diabetes drugs like insulin still worked, proving the effect was specific to metformin.
When researchers injected very tiny amounts of metformin directly into the brains of diabetic mice, blood sugar levels fell significantly — even at doses thousands of times smaller than usual. This showed the brain is extremely sensitive to the drug.
Why This Discovery Matters
Most diabetes medications target the liver, pancreas, or gut. Finding that metformin works in the brain could open the door to new therapies that act directly on brain pathways.
The study also hints at broader benefits. Metformin is already linked to slowing brain aging. Scientists now wonder if this brain Rap1 pathway is responsible for those effects too.
The Big Picture
This breakthrough changes how experts think about one of the world’s most prescribed drugs. Instead of only targeting organs like the liver and intestines, metformin also taps into the brain’s powerful role in regulating blood sugar — and it does so at very low doses.
As Dr. Fukuda put it:
“These findings give us a new perspective on diabetes treatment and may help us design therapies that are even more effective and precise.”
The research was published in Science Advances and supported by organizations including the National Institutes of Health, American Diabetes Association, and American Heart Association.
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Date: September 10, 2025
Source: Baylor College of Medicine