Diabetes Q&A

Study: Metformin Works in the Gut, Not Bloodstream

New research has found that metformin, a glucose-lowering drug used in the treatment of type 2 diabetes, primarily takes effect within the gut and not within the bloodstream.

"Our clinical trials show that metformin works largely in the lower intestine, reversing half a century of conventional thinking," researchers wrote.
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Despite metformin’s use in diabetes treatment for nearly 60 years, little data exists on how and where the glucose-lowering effects of the drug occur.

In order to further explore the mechanisms behind metformin, researchers conducted a phase 1 and phase 2 trial comparing various dosages of Metformin Delayed Release (MDR)—a form of the drug designed to target the gut and limit exposure to the blood stream—to standard metformin, Extended-Release Metformin (XRM), and placebo.1

In the phase 1 trial involving 20 participants, researchers found that participants given MDR had ∼50% less metformin in their blood than those taking standard metformin and XRM.

In the phase 2 trial of 240 patients with type 2 diabetes, MDR showed a significant, sustained reduction in plasma glucose levels compared to placebo.

"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 MDR to the lower bowel significantly reduces the amount of metformin in the blood, while maintaining its glucose-lowering effect."2

"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," they concluded.

—Michael Potts

Reference:

  1. Buse JB, DeFronzo RA, Rosenstock J, et al. 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. August 2015 [epub ahead of print]. doi: 10.2337/dc15-0488.
  2. Diabetes drug metformin’s primary effect is in the gut, not the bloodstream [press release]. August 18, 2015. http://news.unchealthcare.org/news/2015/August/diabetes-drug-metformin2019s-primary-effect-is-in-the-gut-not-the-bloodstream.