Does Metformin Work in the Gut?

Patient Expert

The drug metformin is one of the most common drugs prescribed to treat type 2 diabetes.  When you’re diagnosed, most physicians prescribe metformin as well as suggesting diet and exercise changes.

But not everyone can tolerate metformin. Some people get diarrhea and nausea, sometimes so severe they stop taking the drug. Starting the drug slowly and then increasing the dosage helps. Taking metformin with meals helps.

But sometimes that’s not enough and you decide to try something else.

Metformin should also not be used if you have impaired kidney function, because the kidney is where the drug is removed, and if your kidneys are impaired, the metformin concentrations might rise too high and cause a serious, sometimes life-threatening, complication called lactic acidosis.

Now a group of researchers have found that they can give metformin in a form that has the same benefits but doesn’t have the same side effects. What they do is coat the metformin with a covering that only dissolves in the lower intestine. This approach is like that of enteric aspirin, which doesn’t dissolve in the stomach and hence doesn’t trigger stomach bleeding, a common side effect of aspirin.

With this form of metformin, which they call metformin DR for “delayed release,” the drug levels in the blood are about half as low as those of regular metformin, but the blood-glucose-lowering effects are the same.

What is interesting about this research is that it suggests that the primary site of action of metformin is in the gut, and not in the liver as has been claimed for some years. Researchers have said that metformin keeps the liver from producing and releasing a lot of glucose, through stimulating a molecule called AMPK.

But the metformin worked even when researchers knocked out the AMPK, suggesting that AMPK might not be important after all.

This new drug has passed Phase 2 clinical trials, which are small trials (in this case 240 patients) to see if a drug is effective, as well as checking its safety. But it still  has to pass Phase 3 trials, which are larger (with up to several thousand patients) and can take several years.

So if you can’t take metformin because of the side effects, or because your kidney function is impaired, you won’t be able to try metformin DR for several years unless you enroll in a clinical study, and the company developing the drug, Elcelyx Therapeutics, is not yet recruiting. There is also a possibility that the drug might not pass the Phase 3 trials. Don’t hold your breath.

Another thing to keep in mind is that one reason metformin is so popular is because it’s cheap, sometimes only $4 for a month’s supply, sometimes free. But any new drug is bound to be expensive, and the higher cost might make it a lot less attractive.

Nevertheless, the idea that metformin might work in the gut and not in the liver is interesting. Another group of researchers proposed a similar idea in 2014. They showed that metformin doesn’t work when it’s given intravenously, even though the blood levels are high.

And often new ways of looking at things result in new ways of treating a disease. Let’s hope this research will lead to new approaches to treating type 2 diabetes. Each new discovery helps.

More articles about metformin:

Could Metformin Actually Protect the Kidneys?

Metformin and Exercise