How does metformin work in your body?

Metformin lowers blood sugar primarily by suppressing glucose production in the liver. The liver normally produces glucose from building blocks such as lactate and glycerol. Multiple research groups confirm that metformin strongly inhibits this process, called gluconeogenesis. That is its most firmly established effect.

How metformin does this is somewhat more complex, and scientists are still debating it. A well-known explanation is that it mildly suppresses a step in the liver cell's energy machinery (the mitochondria). This lowers the energy status of the cell, which in turn slows glucose production. The problem is that this effect has been demonstrated in many studies only at concentrations higher than those found in the blood of someone taking the standard daily dose. Its clinical relevance is therefore not beyond dispute.

A more recently discovered mechanism does appear to occur at lower, clinically relevant doses. Metformin disturbs the balance between oxidation and reduction in the liver cell and inhibits a specific enzyme that converts lactate and glycerol into glucose. This mechanism is considered a better explanation for what actually happens in your body at the usual doses.

Metformin also activates a cellular emergency signal, a kind of energy sensor that is triggered when a cell's energy supply drops. That sensor then sets in motion processes that lead to less fat production in the liver, greater fat burning, and improved insulin sensitivity. However, animal research shows that metformin still works even when this sensor is switched off, so it is not the sole explanation.

In addition, metformin appears to dampen the liver's response to glucagon, a hormone that raises blood sugar. And there are early indications that the gut and gut bacteria also play a role in how the drug works. The latter remains an active area of research without firm conclusions. Metformin is currently being investigated in cancer and other age-related conditions as well, but this is still exploratory and does not yet justify use outside of diabetes.