Diabetes Drug Used for More Than 60 Years Found to Unexpectedly Affect the Brain

A 2025 study found that metformin lowers blood glucose not only through the liver and gut, but also via the brain.

Published in Science Advances, the work identified Rap1 signaling in the ventromedial hypothalamus (VMH) as a key pathway.

In mice lacking Rap1 in that brain region, metformin no longer reduced blood glucose.

Direct delivery of tiny metformin doses into the brain still lowered glucose, pointing to SF1 neurons as part of the mechanism.