Key Points:
- A new study from Kobe University suggests that metformin, a widely used diabetes drug, helps lower blood sugar by pushing glucose into the gut, where gut bacteria convert it into beneficial compounds.
- Researchers found that metformin quadruples glucose excretion into the intestines, reducing inflammation and improving insulin response.
- The findings could explain why metformin is effective in managing type 2 diabetes and may lead to new treatment strategies.
How metformin may affect blood sugar
Metformin has been a cornerstone of type 2 diabetes treatment for decades, yet scientists have long debated exactly how it works.
Most research has focused on its impact on the liver, where it improves insulin sensitivity and reduces glucose production. But new findings from Kobe University in Japan suggest that metformin’s effects extend beyond the liver — it also plays a key role in the gut.
According to a study published in the journal Communications Medicine, metformin causes the body to excrete glucose into the intestines at nearly four times the normal rate.
Once in the gut, this glucose serves as fuel for beneficial bacteria, which break it down into short-chain fatty acids (SCFAs) — compounds previously thought to come only from fiber fermentation. SCFAs improve gut health, reduce inflammation, and enhance insulin sensitivity.
What the study evaluated
The research team analyzed metformin’s effects in both humans and mice. Five adults with type 2 diabetes were given the drug, and researchers measured their glucose excretion into the gut. They also conducted similar experiments in mice, tracking the breakdown of glucose using special isotopes.
Key study findings
The study found that:
- Even individuals not taking metformin excreted some glucose into their intestines (0.41 grams per hour), but metformin-treated individuals excreted nearly four times as much (1.65 grams per hour), demonstrating the drug’s role in enhancing this process.
- In mice, gut bacteria converted the excreted glucose into short-chain fatty acids, which have anti-inflammatory properties and may help regulate blood sugar.
- The glucose excretion process occurred primarily in the jejunum, the middle section of the small intestine.
Metformin significantly increased the movement of glucose from the bloodstream into the gut, revealing a newly recognized way the drug may help regulate blood sugar. The researchers believe this newly discovered mechanism contributes to metformin’s well-documented benefits for people with diabetes.
According to the researchers, metformin may help lower blood sugar not only through the liver but also by promoting glucose excretion into the gut, where it can be metabolized by beneficial bacteria. Senior author Wataru Ogawa, MA, PhD, of Kobe University described this as “a novel symbiotic relationship between the host and its microbiota.”
The study also found that in mice, gut bacteria readily broke down glucose into SCFAs, a process researchers hope to further investigate in humans.
Why this matters
Understanding how metformin lowers blood sugar could lead to new treatments for diabetes and related metabolic conditions. The study’s findings suggest that metformin may promote a healthier gut microbiome, offering additional benefits beyond blood sugar management.
José-Manuel Fernández-Real, MD, PhD, a researcher at the University of Girona who was not involved in the study, noted: “Even a slight rise in SCFA production could enhance gut barrier function, reduce inflammation, and improve insulin sensitivity, all of which are beneficial for managing diabetes.”
Limitations and next steps
While promising, the study had several limitations:
- The human trial included only five participants, meaning larger studies are needed to confirm these results.
- The mouse experiments involved only male rodents, so potential sex differences in glucose metabolism remain unexplored.
- The long-term effects of metformin-induced glucose excretion on gut health and metabolic function were not evaluated.
Future research will examine whether metformin’s impact on gut bacteria can be replicated in larger human studies and whether different diets influence how the drug interacts with the microbiome.
The bottom line
This study provides new insight into how metformin works, highlighting its impact on the gut microbiome as a key factor in its blood-sugar-lowering effects. While metformin remains a cornerstone of diabetes treatment, these findings could pave the way for gut-targeted therapies that enhance its benefits.
For more details, check out the official press release from Kobe University and the full study in Communications Medicine.
Want to learn more about metformin? Read Metformin: Everything You Wanted to Know and Diabetes Medicine: Metformin.
