Novel metformin may be safer in renally impaired diabetics

Last Updated: 2015-09-03

By David Douglas

NEW YORK (Reuters Health) - Delayed-release metformin (Met DR), also know as Elcelyx, is formulated to deliver drug to the lower bowel and may curb the circulation-based side effects of other formulations, according to a recent study.

"The American Diabetes Association and the European Association for the Study of Diabetes recommend metformin as the first-line treatment for type 2 diabetes patients, but there isn't an equally effective oral treatment option for patients with renal impairment who are unable to take the drug because of accumulation in the circulation," co-author of the study, Dr. Mark Fineman of Elcelyx Therapeutics in San Diego, California, wrote in email to Reuters Health.

In the two phase study, published online August 18 in Diabetes Care, Dr. Fineman and colleagues compared the bioavailability and glycemic effect of Met DR to that of immediate release metformin (Met IR) and extended-release metformin (Met XR).

The randomized study of 20 healthy volunteers in Phase 1 found that the bioavailability of 1,000 mg Met DR administered twice a day was about half that of Met IR and Met XR.

In Phase 2, the researchers conducted a dose-ranging study in 240 patients with type 2 diabetes.

After 12 weeks, the researchers found that compared to placebo, all doses of Met DR produced "statistically significant, clinically relevant, and sustained reductions" in fasting plasma glucose (FPG).

Compared to Met XR, Met DR demonstrated about a 40% increase in potency.

The investigators concluded that metformin primarily restricted to the gut effectively lowers plasma glucose levels. In fact, they added, "the gut contribution to glucose lowering may be more important than systemic mechanisms."

"These clinical results provide strong evidence that metformin works in the gut to lower glucose," Dr. Fineman told Reuters Health. "As Metformin DR is engineered to principally target the gut and not the circulation it may mitigate the risk of metformin associated lactic acidosis."

"Based on these results," he concluded, "we are conducting additional clinical trials to support development of this important therapeutic option to patients with type 2 diabetes and moderate renal impairment for whom metformin is currently contraindicated."

This study was commissioned and funded by Elcelyx Therapeutics. Four of the eight authors are employees of the company.

SOURCE: http://bit.ly/1LjZSST

Diabetes Care 2015.