Every year, more than 80 million prescriptions for the common diabetes drug metformin are dispensed in the U.S., making it one of the most prescribed medications in the country. However, researchers are still learning how the drug actually produces its blood-sugar-lowering effects in the body, decades after its U.S. approval and distribution in the 1990s.
Based on years of research, experts believed that metformin’s main strategy was telling the liver to stop releasing extra sugar into the blood, thereby lowering the overall concentration that can cause harm over the long term, the core issue behind type 2 diabetes. But a new study conducted by Northwestern University and published in Nature Metabolism suggests an entirely different location where metformin influences blood sugar levels: the gut.
“Metformin essentially helps the intestine suck the glucose out of the bloodstream, which further highlights that the gut plays a major role in regulating blood sugar levels,” said study co-author Navdeep Chandel, professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine, in a press release.
Metformin Acts on Blood Sugar Levels Already in the Gut
Sugar, or glucose when referring to its basic molecular form, is the most important source of energy for the body. It’s the fuel our cells run on to carry out basic molecular functions, but our bodies can get overwhelmed when there is too much glucose. Chronically high blood sugar levels can desensitize the insulin response (the hormone that directs where in the body absorbed glucose needs to go) and can lead to tissue damage.
Previous research already showed that metformin intervenes with glucose after it enters the cell by blocking part of the energy-producing machinery, the mitochondrion. When studying the effects of metformin more closely using human data and testing mice, the team observed that metformin works its cellular magic in the gut, before it reaches the liver.
“Our study suggests that revisiting assumptions about metformin’s mechanism may offer a more detailed understanding of how it works,” said the study’s first author, Zach Sebo, in the statement. Their findings also show how future drug and supplement research should consider targeting the gut to effectively lower blood sugar levels.
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Patient Observations Confirm Gut Pathway
The researchers’ discovery on a molecular basis also lines up with common clinical observations in people who take metformin, further supporting their theory. Chandel describes how patients taking metformin can show lower blood sugar levels right after they eat because the drug enables the gut to “soak up” the extra glucose from the meal.
Other evidence comes from lower concentrations of citrulline and higher levels of the appetite-regulating hormone GDF15 in people taking metformin. Both compounds’ release depends on the performance of mitochondria in the gut.
“People have always wondered how one drug can do 10 things,” said Chandel. “Well, it can do that if the drug is hitting a big node in a cell, and hitting mitochondria in a cell is a big node. So, if you can get into those cells and inhibit mitochondria, it's going to have huge effects.”
Nature’s Ozempic Berberine Works Like Metformin
Through their discovery, the researchers saw a connection to a popular over-the-counter supplement dubbed “Nature’s Ozempic.” According to Cleveland Clinic, this plant-derived compound called berberine has been used for centuries in traditional medicine and may support weight loss and lower blood sugar levels.
Their study found that berberine may operate through the same gut-related mechanism as metformin. Nonetheless, experts are still hesitant to embrace the substance’s health claims, warning people not to consider a supplement a replacement for approved medication.
“Metformin has decades of clinical evidence behind it, whereas supplements like berberine are far less rigorously tested,” explained Chandel. “If you're going to use berberine, you may as well use the real deal.”
This
article is not offering medical advice and should be used for informational
purposes only.
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Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
- This article references information from a study published in Nature Metabolism:Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control
- This article references information from the Cleveland Clinic: Berberine: What It Is, Benefits and Side Effects