- A new mouse study suggests metformin may work primarily by acting on cells in the gut rather than mainly on the liver.
- The researchers found the drug appears to make intestinal cells use up more glucose by interfering with their energy production.
- It is an important mechanistic finding, but it comes from mice and does not overturn decades of clinical practice overnight.
Metformin has been used for decades, but scientists have never completely agreed on how it works.
The usual explanation has been that it mainly acts on the liver to reduce glucose production.
A new study suggests the gut may be the more important target.
Researchers found that metformin seems to block part of the mitochondria’s energy machinery in intestinal cells.
That forces the gut to use more glucose itself.
In simple terms, the intestine starts acting like a sponge, pulling more glucose out of the bloodstream.
The team tested this in mice engineered so that their gut cells were resistant to this mitochondrial effect.
In those mice, metformin lost much of its glucose-lowering power.
That strongly suggests the gut is not just involved, but central to the drug’s action.
The finding also helps explain a few long-standing clinical observations.
People on metformin often have lower blood sugar after meals.
They also tend to have lower citrulline levels and higher GDF15, both of which make more sense if the drug is stressing intestinal metabolism.
- Metformin may help some people with type 1 diabetes use less insulin
- Metformin may mimic some exercise-related metabolic effects in prostate cancer care
- Metformin may lower blood sugar through the brain as well as the body
The study also found parallels with berberine, a popular supplement sometimes marketed online as a natural alternative to diabetes drugs.
The researchers say berberine may be acting through the same pathway, although metformin has the far stronger evidence base.
This is a mouse study, so caution is needed.
But it is a serious piece of work and it adds to a growing shift in how metformin is understood.
The drug may still be old, but it clearly still has surprises left in it.
