A new study shows that the glucose-lowering effect of metformin – a drug used to treat type 2 diabetes – takes place in the gut and not in the bloodstream.

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Type 2 diabetes patients with impaired kidneys cannot take the current version of metformin.

The revelation, published in the journal Diabetes Care, means that a delayed-release form of metformin that the researchers tested could suit the 40% of type 2 diabetes patients who cannot use the current formulation.

Metformin (short for metformin hydrochloride, also known as Glucophage and other brand names) has been used in the treatment of type 2 diabetes for nearly 60 years.

Despite the drug’s veteran status, scientists are not exactly sure how and where in the body most of its glucose-lowering effect takes place.

The new study, led by the University of North Carolina School of Medicine at Chapel Hill, provides strong evidence that metformin does most of its work in the gut, and not in the bloodstream, as many had assumed.

First author John Buse, a professor of medicine, says:

“Our clinical trials show that metformin works largely in the lower intestine, reversing half a century of conventional thinking.”

In their paper, the team describes how they carried out a phase 1 and a phase 2 trial of the experimental drug Metformin Delayed Release (Metformin DR). Prof. Buse says:

“These studies provide evidence that delivering Metformin DR to the lower bowel significantly reduces the amount of metformin in the blood, while maintaining its glucose-lowering effect.”

One of the main reasons metformin is not suitable for all patients with type 2 diabetes is because it collects in the blood of those with poor kidney function, raising the risk of a life-threatening condition called lactic acidosis, where lactic acid builds up in the bloodstream faster than it can be removed.

There are currently around 4 million people in the US with type 2 diabetes who cannot take metformin because of impaired kidneys.

In the phase 1 trial, the researchers compared single daily doses of Metformin DR to immediate-release metformin (Metformin IR) and extended-release metformin (Metformin XR) in 20 healthy subjects who were each randomly assigned to receive one of the three treatments.

The results showed that participants who took the DR version had half the amount of metformin in their blood compared with those who took the IR or XR versions.

In the phase 2 trial, the researchers tested the effects of various doses of Metformin DR against placebo or Metformin XR in a total of 240 type 2 diabetes patients at various clinics.

They found that Metformin DR was around 40% more potent than Metformin XR. Metformin DR also showed a statistically significant and sustained reduction in fasting plasma glucose over 12 weeks compared with placebo.

The researchers note that for most patients, the treatment was well tolerated, and the side effects were much the same as those already known to occur with current forms of metformin. Prof. Buse concludes:

These findings create an opportunity to develop a new metformin treatment option for the 40% of patients that currently can’t take this first-line drug of choice.”

Last year, Medical News Today learned that taking metformin may help people live longer.