WEDNESDAY, Nov. 17 (HealthDay News) -- Using the controversial diabetes drug Avandia as an example, new research finds that doctors' prescribing patterns vary across the country in response to warnings about medications from the U.S. Food and Drug Administration.

The result is that patients may be exposed to different levels of risk depending on where they live, the researchers said.

"We were looking at the impact black-box warnings for drugs have at a national level, and, more specifically, at a geographical level, and how these warnings are incorporated into practice," said study lead researcher Nilay D. Shah, an assistant professor of health services research at the Mayo Clinic in Rochester, Minn.

In 2007, the FDA required that Avandia come with a "black-box warning" -- the strongest warning possible -- alerting consumers that the drug was associated with an increased risk of heart attack.

Before the warning, Avandia was widely prescribed throughout the United States, although regional differences existed. "There was about a two-fold difference in use before the warning -- around 15.5 percent use in Oklahoma versus about 8 percent in North Dakota," Shah said.

Right after the warning, the use of Avandia dropped dramatically, from a nationwide high of 1.3 million monthly prescriptions in January 2007 to roughly 317,000 monthly prescriptions in June 2009.

"There was a huge decrease in use across the country," Shah said. "But there was quite a bit of residual use."

After the FDA warning, the researchers still found as much as a three-fold difference in use across the nation. In Oklahoma, Avandia use dropped to about 5.6 percent, but in North Dakota it tumbled to 1.9 percent, Shah said.

The reasons for the differences aren't clear. Some factors might include how doctors are made aware of FDA warnings and how they react. Another factor could be the policy of state health insurance plans, including Medicaid, in terms of covering drugs, he said.

Also, prominent doctors in given areas can influence the choice of drugs other doctors make, Shah said. And drug-company marketing may play a role, he said.

"At this point we don't have good insight into these differences," he said.

This problem isn't unique to Avandia, Shah said. "This is not uncommon with a lot of drugs," he said. "This is a good case example."

The report was published in the Nov. 17 edition of the New England Journal of Medicine.

The study also found that the American Diabetes Association's January 2009 consensus statement advising against prescribing Avandia appeared to have had a "negligible influence" on trends in its use.

The study authors think the FDA could do a better job of alerting all doctors about warning labels. "The FDA could provide a tool for doctors and patients to show the risks and benefits of going on the drug," Shah said.

As for Avandia, in September the FDA introduced further restrictions on use of the drug. The agency is requiring Avandia's maker, GlaxoSmithKline, to develop a program that will limit access to the drug to patients for whom other treatments have not worked.

Also, doctors will have to state and document a patient's eligibility to use Avandia. They will also have to tell patients about the cardiovascular safety risks associated with Avandia, and patients will have to acknowledge that they understand those risks.

Commenting on the new study, Dr. Luigi Meneghini, professor and director of clinical operations in the division of endocrinology, diabetes and metabolism at the University of Miami Miller School of Medicine, said "there was still some confusion about the negative effects of Avandia."

"Physicians tend to be skeptical and not change their habits unless there is solid evidence, and with Avandia the evidence was not as solid as one would want," he said. "But, for the majority of physicians there was clearly a change in the way they prescribe."

With the new restrictions the FDA has placed on Avandia, Meneghini believes that very few doctors will be prescribing the drug anymore.

Meneghini added that the FDA is pretty good at getting warning information out to doctors. "Whether the warning is heeded depends on the availability of the drug, the importance of the drug and patient desires," he said.

Also, many doctors stopped prescribing Avandia when the warning came out due to fear of liability, Meneghini said. "That drove a lot of the decisions," he said.

More information

For more on Avandia, visit the U.S. National Library of Medicine.