Metformin is one of the most widely used medicines in the world. Millions of people with type 2 diabetes take it every day to help control their blood sugar levels.
Doctors have prescribed this medication for decades because it is affordable, effective, and generally considered safe. Even though metformin has been used for so long, scientists have still been trying to fully understand exactly how it works inside the body.
For many years, researchers believed metformin mainly worked by targeting the liver. The common explanation was that the drug lowered blood sugar by reducing the amount of glucose produced by the liver. This idea became widely accepted in medicine and was taught for decades.
Now, a new study from Northwestern University is challenging that long-standing belief. The new research suggests that metformin may actually work mainly in the gut rather than the liver. The study was carried out in mice and published in the journal Nature Metabolism.
The researchers found that metformin appears to act directly on cells lining the intestine. Instead of mainly blocking sugar production in the liver, the drug may help the intestine pull more glucose out of the bloodstream and use it for energy.
Glucose is the body’s main fuel source. After people eat, carbohydrates are broken down into glucose, which enters the bloodstream. The body then uses insulin to move this glucose into cells where it can be used for energy.
In people with type 2 diabetes, this system does not work properly. Blood sugar levels remain too high, which over time can damage blood vessels, nerves, kidneys, eyes, and other organs.
The Northwestern researchers discovered that metformin changes the way intestinal cells produce energy. Inside cells are tiny structures called mitochondria, which are often described as the cell’s power plants. They help turn nutrients into usable energy.
The study found that metformin slows down part of the mitochondria’s energy production process in gut cells. Because of this slowdown, the intestine begins burning more glucose for fuel. This helps remove extra sugar from the bloodstream.
Professor Navdeep Chandel, one of the lead researchers, explained that the intestine may act almost like a sponge, soaking up excess sugar from the blood after meals. This could explain why many people taking metformin often have lower blood sugar after eating.
The research also helps explain several puzzling effects doctors have observed in metformin users over the years. For example, people taking metformin often have lower levels of a substance called citrulline.
Citrulline is produced in the small intestine by mitochondria. If metformin slows mitochondrial activity, citrulline production naturally decreases.
The study also helps explain why metformin increases levels of a hormone called GDF15. This hormone is linked to reduced appetite and weight loss. Researchers believe the gut senses stress in its energy system and responds by releasing signals that affect hunger and metabolism.
Another interesting part of the study involved berberine, a plant-based supplement that has become popular online for blood sugar control. Some social media users even call berberine “nature’s Ozempic.” However, many medical experts warn that berberine has not been tested as carefully as prescription medications.
The Northwestern team discovered that berberine may affect the same biological pathway as metformin in the intestine. Still, the researchers emphasized that metformin has decades of strong clinical evidence supporting its safety and effectiveness, while supplements like berberine are much less studied.
To perform the research, scientists used genetically modified mice. The mice were engineered so that some intestinal cells were protected from metformin’s effects on mitochondria. In those mice, metformin lost much of its ability to lower blood sugar levels. This gave strong evidence that the gut is one of the drug’s main targets.
The findings may change how scientists think about diabetes treatment in the future. Instead of focusing mainly on the liver, researchers may now explore ways to target the gut more directly to control blood sugar.
The study also shows how one medicine can produce many different effects throughout the body. By affecting mitochondria, metformin may influence blood sugar, appetite, weight, and metabolism all at once.
The findings are exciting because they provide a more complete understanding of one of the world’s most important diabetes medications. At the same time, the research was conducted in mice, so more studies in humans will still be needed before scientists can fully confirm how the drug works in people.
Overall, the study provides strong evidence that the intestine may play a much larger role in blood sugar control than previously believed. It may also help scientists develop better diabetes treatments in the future that work more directly through the gut while reducing side effects.
If you care about blood sugar, please read studies about why blood sugar is high in the morning, and how to cook sweet potatoes without increasing blood sugar.
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Source: Northwestern University.
