Revealed After 60 Years, Diabetes Medicine Turns Out to Affect the Brain

JAKARTA - For more than six decades, metformin has been one of the main drugs in the treatment of type 2 diabetes. This drug is widely known for its ability to lower blood sugar levels by reducing glucose production in the liver and increasing insulin sensitivity.

However, behind its long-term use, the mechanism of metformin's work has not been fully understood until now.

The latest research from the Baylor College of Medicine in the United States in 2025 revealed a surprising finding, metformin apparently works directly on the brain. This finding opens up new perspectives in the medical world, especially in the development of more effective diabetes therapies.

Makoto Fukuda, a pathophysiologist involved in the study, explained that scientists have focused on the liver and intestines as the main targets of metformin. However, recent research is turning its attention to the brain as the center of regulation of the body's metabolism.

"It has been widely accepted that metformin lowers blood glucose levels mainly by reducing glucose production in the liver. Other studies have also found that this drug works through the gut," said Fukuda, quoted from the Science Alert website.

"We study the brain because it is known as the main regulator of the whole body's glucose metabolism," he continued.

In the study, scientists found that metformin works through a specific pathway in the brain, specifically in a part called the ventromedial hypothalamus (VMH). In this area there is a protein called Rap1 which plays a role in glucose metabolism.

Experiments in mice show that metformin is able to reach the VMH and deactivate Rap1. This effect is proven to be important, because when mice are engineered without the Rap1 protein, metformin no longer provides benefits against diabetes-like conditions.

This finding is strong evidence that metformin has a different mechanism of action than other diabetes drugs. Furthermore, the researchers also identified a specific type of nerve cell involved in this process, namely the SF1 neuron. Activation of these neurons seems to be the key to metformin's antidiabetic effect in the brain.

"We found that SF1 neurons are activated when metformin enters the brain, suggesting that these neurons are directly involved in the way the drug works," said Fukuda.

This discovery not only broadens our understanding of metformin, but also opens up opportunities to create more specific therapies. By targeting specific neurons, future treatments have the potential to be more effective and have fewer side effects.

In addition to its benefits in controlling diabetes, metformin is also known to have other interesting effects, including slowing the aging process. This drug is even categorized as geroprotective, that is, a drug that can slow down various aging mechanisms in the body.

A number of studies have shown that metformin can reduce DNA damage, increase the activity of genes related to longevity, and protect brain function.

In another study in 2025 involving more than 400 postmenopausal women, metformin was compared with another diabetes drug, namely sulfonylurea. The results were quite striking.

"The group using metformin has a 30 percent lower risk of dying before the age of 90 compared to the sulfonylurea group," he said.

This finding strengthens the suggestion that metformin not only serves as a diabetes drug, but also has the potential to improve quality and life expectancy.

However, the use of metformin still has side effects that need to be considered. Digestive disorders such as nausea, diarrhea, and abdominal discomfort are quite common, even up to 75 percent of users experience them. Additional risks can also arise in individuals with impaired kidney function.

However, overall, metformin is still considered one of the relatively safe and effective therapies. With this new discovery, scientists are now looking at metformin from a different perspective. Not just as a drug that works in the liver or intestines, but also as an agent that affects the central system in the brain.

"This discovery changes the way we look at metformin," said Fukuda.

"This drug not only works in the heart or intestines, but also in the brain." he continued.

If further studies in humans can confirm these findings, it is not impossible that metformin will be used for various other medical purposes in the future, ranging from metabolic therapy to protection against brain aging.

This research is an important step in understanding the relationship between the brain and the body's metabolism, as well as paving the way for more sophisticated and targeted treatment innovations.