(HealthDay News) — Metformin may act via a predominantly lower bowel-mediated mechanism, according to research published online August 18 in Diabetes Care.

John B. Buse, MD, PhD, from the University of North Carolina School of Medicine at Chapel Hill, and colleagues conducted two studies to assess delayed-release metformin (Met DR). The first study compared the bioavailability of single daily doses of Met DR with immediate-release metformin (Met IR) and extended-release metformin (Met XR) in 20 otherwise healthy volunteers. The second examined glycemic control in 240 individuals with type 2 diabetes mellitus over 12 weeks.

The researchers found that the bioavailability of 1,000mg Met DR was about half of that of Met IR and Met XR. In the second study, there were significant, clinically relevant, and sustained reductions in fasting plasma glucose levels over 12 weeks with Met DR (600, 800, and 1,000mg) compared with placebo, with about a 40% increase in potency vs. Met XR. At 12 weeks, the placebo-subtracted changes from baseline in hemoglobin A1c were consistent with fasting plasma glucose changes. Treatments were generally well tolerated.

“Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action,” the authors write.

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Several authors disclosed financial ties to pharmaceutical companies, including Elcelyx Therapeutics, which funded the study.

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