New York: In a major breakthrough, researchers have found that the common diabetes drug metformin’s primary effect occurs in the gut and not the bloodstream as previously thought.

The findings create an opportunity to develop a new metformin treatment option for the 40 percent of Type 2 diabetes patients who currently cannot take metformin.

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.

Researchers, however, still debate precisely how the drug works.

“Our clinical trials show that metformin works largely in the lower intestine, reversing half a century of conventional thinking,” said John Buse, first study author and director of the diabetes care centre at University of North Carolina.

The paper, appeared online in the journal Diabetes Care, 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.

One of the top reasons metformin is not 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.

“The new findings show that delivering Metformin DR to the lower bowel significantly reduces the amount of metformin in the blood, while maintaining its glucose-lowering effect,” Buse stressed.

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 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.

The phase 1 randomized study involved 20 healthy subjects.

In the phase 2 study, various doses of Metformin DR were compared to placebo or Metformin XR in patients with Type 2 diabetes.

Metformin DR exhibited a 40 percent increase in apparent potency compared to Metformin XR.

“Also, Metformin DR exhibited statistically significant and sustained reductions in fasting plasma glucose levels over 12 weeks compared to placebo,” the authors noted.

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.

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 findings hold promise for millions suffering from Type 2 diabetes worldwide which results mostly from wrong lifestyle and food habits.

India leads the world with largest number of diabetic people, earning the dubious distinction of being termed the “diabetes capital of the world”.

The number of diabetic patients in Indian are expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken.