A common diabetes drug metformin's primary effect occurs in the gut and not the bloodstream, scientists have found, reversing half a century of conventional thinking.
The findings could create a new metformin treatment option for the 40 per cent of patients who currently can not take this first-line drug of choice, the researchers said.
Metformin was introduced as a treatment for type 2 diabetes nearly 60 years ago and is now the recommended first-line treatment for newly diagnosed patients.
The study provides strong evidence that metformin's primary effect occurs in the gut, not the bloodstream.
The study outlines results from phase 1 and phase 2 studies involving the investigational drug Metformin Delayed Release (Metformin DR), which is designed to target the lower bowel and limit absorption into the blood.
"Our clinical trials show that metformin works largely in the lower intestine, reversing half a century of conventional thinking," said first author John Buse, professor of medicine, and director of the Diabetes Care Centre at the University of North Carolina School of Medicine in US.
"One of the top reasons metformin isn't used for all people with type 2 diabetes is that patients with impaired kidneys accumulate too much drug in the blood, and this can result in life-threatening lactic acidosis," Buse said.
"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," he said.
Because of this, Metformin DR may prove to be a treatment option for the four million type 2 diabetes patients in the US with impaired kidney function, researchers said.
In the phase 1 study, single daily doses of Metformin DR were compared to immediate-release metformin (Metformin IR) and extended-release metformin (Metformin XR) in 20 healthy volunteers.
The amount of metformin in the bloodstream after Metformin DR treatment was approximately half the amount seen with Metformin IR or Metformin XR.
In the phase 2 study, doses of Metformin DR were compared to placebo or Metformin XR in patients with type 2 diabetes.
Metformin DR exhibited a 40 per cent increase in apparent potency compared to Metformin XR. Metformin DR exhibited statistically significant and sustained reductions in fasting plasma glucose levels over 12 weeks compared to placebo.
Treatment was generally well tolerated, with adverse events consistent with those for currently available metformin products.
The phase 2 randomised trial included 240 patients with type 2 diabetes at multiple study centres. Patients received either 600, 800 or 1,000 mg of Metformin DR once daily, blinded placebo, or unblinded Metformin XR at 1,000 or 2,000 mg per day.
The study was published in the journal Diabetes Care.
