Metformin-Avandia Combo Slows Progression to Type 2 in Two-Thirds of At-Risk Patients

A Canadian study that tracked 207 patients suggests that a low-dose combination of metformin and Avandia can reduce the development of type 2 diabetes by 66 percent in people at high risk for the condition.

Researchers at the University of Toronto (funded by Avandia’s manufacturer, GlaxoSmithKline) selected 207 people with impaired glucose tolerance, which is a precursor to type 2, and gave them either the Avandia-metformin combination or a placebo over a four-year period. The drugs were administered daily in doses of 2 mg of Avandia and 500 mg of metformin.  Typical daily doses for each drug, if taken as a standalone, are 4 to 8 mg for Avandia and 1,000 to 2,000 mg for metformin.

At the end of the study, the Canadian researchers found that 14 percent of the patients receiving the drug combination had developed type 2, versus 39 percent of the patients on placebo. This means that the Avandia-metformin recipients had only about one-third as much risk of acquiring type 2.

Other studies have shown that metformin alone reduces the risk of acquiring type 2 by 30 percent. Avandia has been shown to produce a risk reduction of up to 60 percent, but that success rate has come with some concerns. Part of the reason for using both drugs in low doses was to avoid negative side effects that have been associated with both drugs, particularly Avandia, at regular dosages.

Avandia (GlaxoSmithKline’s trade name for rosiglitazone) works to sensitize the body to insulin, helping it establish better control of blood glucose. Sales of Avandia, which was first marketed in 1999, reached a $2.2 billion peak in the U.S in 2006. But subsequent concerns that the drug increases the risk of heart disease and heart attack cut into sales, which dropped to $660 million by 2009.

Metformin, which lowers blood sugar levels, has long been the first “go-to” drug in doctors’ apothecary for treating newly diagnosed type 2. It is also increasing in favor as a drug for treating pre-diabetes and gestational diabetes. Its side effects are fairly benign, including stomach upset and diarrhea.

Although the results from such a small sample are not definitive, they suggest a way in which Avandia might be able to regain some market share, especially in the burgeoning field of pre-diabetes care. The possibility of using a low-dose therapy to stave off type 2 is attractive, but it is not a cure. That outcome awaits better insights into how the body develops insulin resistance and pancreatic beta cell disease.

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