Metformin, introduced as a treatment for type 2 diabetes nearly 60 years ago, is now the recommended first-line treatment for newly diagnosed patients, but researchers are still debating on exactly how the drug works.

Now, a new study from researchers at the University of North Carolina School of Medicine, Elcelyx Therapeutics, and other leading endocrinologists shows strong evidence that metformin’s primary effect happens in the gut, not the bloodstream.

The paper outlines results from phase 1 and phase 2 studies involving the investigational drug Metformin Delayed Release (Metformin DR), designed to target the lower bowel and limit absorption into the blood.

First author John Buse, MD, PhD, professor of medicine, and director of the Diabetes Care Center at the University of North Carolina School of Medicine, says:

“Our clinical trials show that metformin works largely in the lower intestine, reversing half a century of conventional thinking. These findings create an opportunity to develop a new metformin treatment option for the 40 percent of patients that currently can’t take this first-line drug of choice.

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. 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."

For that reason, Metformin DR may prove to be a treatment option for the four million type 2 diabetes patients in the United States with impaired kidney function.

John B. Buse, Ralph A. DeFronzo, Julio Rosenstock, Terri Kim, Colleen Burns, Sharon Skare, Alain Baron, and Mark Fineman The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation. Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies Diabetes Care, doi:10.2337/dc15-0488

Image: Alex Williamson, Wellcome Images

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