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New Study Shows Metformin Resides in Gut, Not Circulation

Even though metformin delayed release resides in gut, it still maintains glucose-lowering effect…

Metformin has been known to be the first line treatment for type 2 diabetes if the side effects are tolerable. According to new study published by Diabetes Care, metformin delayed release (metformin DR) primary effect is in the gut, not the circulation. Comparison of the formulations were done into two studies.

Twenty healthy volunteers participated in study 1, a phase 1 randomized trial, which was designed to compare the bioavailability of single daily doses of metformin DR to metformin immediate-release (metformin IR) and metformin extended-release (metformin XR).

Study 2 was a phase 2, multicenter, placebo-controlled trial that included 240 type 2 diabetes (T2DM) patients; it was designed to determine glycemic control. The randomized group received metformin DR 600, 800, or 1,000 mg once daily; blinded placebo; or unblinded metformin XR 1,000 or 2,000 mg for over 12 weeks.

In phase 1 study, the bioavailability of metformin DR in the bloodstream was half compared with patients who received metformin IR or metformin XR.

In the phase 2 study, metformin DR showed a 40 percent increase in potency compared to metformin XR. Furthermore, metformin DR had statistically significant and prolonged decrease in fasting plasma glucose levels compared with placebo over the 12 weeks. “All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information,” said the researchers.

In conclusion, according to the researchers, dissociation of the glycemic effect from plasma exposure with gut-restricted [metformin] DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.

Practice Pearls:

  • Cautions in patients with kidneys impairment
  • Metformin DR showed a 40% increase in potency compared to metformin XR.

Buse, John B., 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 Dia Care (2015): Dc150488.