Diabetes Drug Metformin: For several decades, metformin has been a standard medication for managing type 2 diabetes. New findings reported in Science Advances by a team from Baylor College of Medicine and international partners suggest the drug may act in an unexpected way which is by directly affecting the brain. As reported in Science Alert, metformin inhibits a protein known as Rap1 within the brain responsible for regulating energy balance and blood sugar levels.

The study also showed that SF1 neurons become active when the drug is present in the brain, stating they likely play a role in how metformin produces its effects. Prescribed for Type 2 diabetes, metformin is a cheap medicine with a prolonged effect that works by reducing glucose production in the liver while also enhancing the body’s sensitivity to insulin, allowing it to regulate blood sugar.

"It’s been widely accepted that metformin lowers blood glucose primarily by reducing glucose output in the liver,” noted associate professor of pediatrics and nutrition at Baylor and the study’s corresponding author, Dr Makoto Fukuda.

“Other studies have found that it acts through the gut. We looked into the brain as it is widely recognised as a key regulator of whole-body glucose metabolism,” he added.

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Metformin's Affect On Brain

In 2025, researchers from Baylor College of Medicine identified a unique neural pathway that may explain how the drug functions in the brain, adding to the understanding of its effects throughout the body.

"This discovery changes how we think about metformin. It’s not just working in the liver or the gut, it’s also acting in the brain. We found that while the liver and intestines need high concentrations of the drug to respond, the brain reacts to much lower levels,” said Fukuda.

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As per Fukuda, the new knowledge can help create new medication for diabetes that affect the concerned route in the brain.

"In addition, metformin is known for other health benefits, such as slowing brain aging. We plan to investigate whether this same brain Rap1 signaling is responsible for other well-documented effects of the drug on the brain,” he said.