Avandia: Less Risky in Younger, Healthier Patients?

Study Finds Avandia No Riskier Than Actos, Unlike 4 Other Studies

From the WebMD Archives

Aug. 24, 2010 -- A study of patients enrolled in a large HMO finds no evidence that the diabetes drug Avandia is riskier than Actos, a similar medication.

The findings are in striking contrast to four other large studies with similar designs. Data from those studies suggest that Avandia increases risk of heart attack in younger patients and risk of death in older patients.

The new study isn't entirely new. It's an "enhanced version" of data presented to an FDA advisory committee in 2007. Like the earlier version, it finds Avandia is no riskier than Actos, says study author Debra A. Wertz, PharmD, of HealthCore Inc.

"Looking at a composite endpoint of heart attack, acute heart failure, and death, we observed no significant differences between the two agents in our study population," Wertz tells WebMD.

Why did the results differ so markedly from other studies with similar designs?

"All of these studies have different methodologies and different observational data," Wertz says. "Our particular study did look at a commercially insured population that may be healthier and younger than others."

Indeed, a recent study by FDA safety researcher David Graham, MD, and colleagues found that Medicare patients with diabetes were at significantly greater risk of death if they took Avandia rather than Actos. But those patients were all over age 65, with an average age of 74.4.

In the Wertz study, patients' average age was 54. And they were all privately insured, suggesting that even the older patients in the study were more likely to be employed and thus relatively healthy.

Aviandia Study 1 Piece of the Puzzle

Steven Nissen, MD, the Cleveland Clinic cardiologist who was among the first to warn of Avandia's possible heart risks, says the Wertz findings cannot be considered in isolation.

"There is a consistent pattern of excess risk with [Avandia] apparent in multiple observational studies and meta-analyses performed by independent physician-scientists and the FDA," Nissen tells WebMD via email. "The totality of data continue to demonstrate that [Avandia] increases adverse cardiovascular outcomes in comparison to [Actos]."

Even so, Wertz says the new study is important and will be helpful to patients and their doctors in deciding which diabetes treatment is best for them.

Continued

Leanne Chrisman, MD, a diabetes specialist at Cleveland's University Hospitals Case Medical Center, agrees that diabetes patients have to find out what works for them as individuals.

"Medications alter the body's chemistry, and not everybody's chemistry is exactly the same," Chrisman tells WebMD. "Some day there will be some kind of blood test that tells you which drug will work the best for you, but at this point, we can't do that."

Instead of expecting their doctors to tell them what to do, Chrisman says patients have to work with their doctors in a constant back-and-forth. If a drug isn't doing what it's supposed to -- or has a side effect -- patients have to report back to their doctor so that they can try something else.

And diabetes drugs, Chrisman says, are only one leg of the unbalanced three-legged stool on which diabetes patients perch. The other two legs are diet and exercise.

"If you don't pay attention to any one of those legs, they will fall over," she says. "You can try to balance for a while, but it will fall over if you don't pay attention to what impacts you most."

Nissen notes that there is no evidence that Avandia offers any unique benefits not seen with Actos.

In July, an FDA advisory panel split over whether to recommend that Avandia be taken off the market. Twelve of the panel's 33 members said the drug should be withdrawn; all but three others recommended that the drug carry more severe safety warnings.

Final action by the FDA is pending. Meanwhile, a clinical trial directly comparing Avandia and Actos is on hold while the FDA grapples with the issue of whether it can ethically continue.

The Wertz study appears in the American Heart Association journal Circulation Cardiovascular Quality and Outcomes.

WebMD Health News Reviewed by Laura J. Martin, MD on August 24, 2010

Sources

SOURCES:

Wertz, D.A. Circulation Cardiovascular Quality and Outcomes, published online Aug. 24, 2010.

Debra A. Wertz, PharmD, HealthCore Inc., Wilmington, Del.

Leanne Chrisman, MD, family medicine practitioner and diabetes specialist, University Hospitals Case Medical Center, Cleveland.

Steven E. Nissen MD, chairman, department of cardiovascular medicine, Cleveland Clinic.

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