After 60 years, scientists uncover metformin’s hidden brain effects - ScienceDaily

What the report says

ScienceDaily, citing materials from Baylor College of Medicine, reported on July 25, 2026, that researchers have identified a brain-related mechanism that may help explain how metformin lowers blood sugar. Metformin has long been used as a first-line treatment for type 2 diabetes, with much of its effect traditionally linked to the liver and, in more recent research, the gut. The new study, published in Science Advances, points to a role for the ventromedial hypothalamus, a brain region involved in whole-body glucose regulation.

The research team, led by corresponding author Dr. Makoto Fukuda of Baylor, focused on Rap1, a protein in that hypothalamic region. In experiments using genetically engineered mice on a high-fat diet, low-dose metformin did not improve blood sugar when Rap1 was absent in the targeted brain area. Other treatments, including insulin and GLP-1 agonists, still worked, suggesting the finding was specific to metformin’s pathway.

Researchers also tested very small amounts of metformin delivered directly into the brains of diabetic mice and reported significant glucose-lowering effects at doses far below typical oral exposure. Further tissue studies indicated that metformin activated SF1 neurons in the ventromedial hypothalamus, but this response depended on Rap1 being present.

The findings matter because they suggest metformin may act partly through a central nervous system pathway, not only through peripheral organs. However, the evidence described in the report comes from preclinical mouse and tissue experiments, so it does not by itself establish a new treatment approach for patients. The authors said the work could guide future diabetes therapies that more directly target this brain pathway.