Metformin Lowers Glucose Through Brain Rap1 Pathway at 1 μg Dose, Study Finds

1 articles · Updated · ScienceAlert · Aug 1

Science Advances reported that metformin lowered blood glucose in mice through the brain’s ventromedial hypothalamus, where the drug activated SF1 neurons via the Rap1 pathway.
Rap1 deletion in that brain region blocked metformin’s glucose-lowering effect in high-fat-diet mice, even though the animals still responded to insulin and GLP-1 agonists.
A 1 μg metformin dose injected directly into obese mice’s brains significantly reduced blood glucose, suggesting the brain is highly sensitive to the drug compared with oral or peripheral dosing.
The findings challenge the long-held view that metformin works mainly through the liver and gut and point to brain-targeted diabetes treatments; researchers also plan to test whether the same pathway underlies reported anti-aging brain effects.