Dec. 11 --
WEDNESDAY, Dec. 10 (HealthDay News) -- Two widely prescribed diabetes drugs, Avandia and Actos, double the risk of fractures in women but not in men, a new British analysis finds.
Avandia (rosiglitazone) and Actos (pioglitazone) are used to lower blood sugar in patients with type 2 diabetes. Recent studies have suggested that the risk for heart failure, death and heart attack were increased with Avandia, touching off a controversy that resulted in new U.S. Food and Drug Administration-mandated label warnings about the drug.
"Women who are taking these drugs should reconsider the options," said lead researcher Dr. Yoon Loke, a clinical senior lecturer at the University of East Anglia in Norwich. "There are quite a lot of choices for women with type 2 diabetes. I am not sure that taking a drug that causes fractures is the best choice."
There are about 4 million people in the United States who take these drugs, which are called thiazolidinediones, Loke noted.
The report was published in the Dec. 10 online issue of the Canadian Medical Association Journal.
For the meta-analysis, Loke's team evaluated 10 trials that included 13,715 diabetics taking Avandia, Actos, or neither drug. The studies found that these drugs reduced bone density in the spine and hips of women taking these medications.
Loke's group estimated this loss of bone density would double the risk of fractures in women taking either drug. For women already at risk for fractures, the researchers estimated one fracture would occur for every 21 women, and for those at low risk for fractures, one fracture would occur in 55 women taking these drugs.
However, no effect on bone density among men was seen in any of the studies the researchers analyzed.
Loke speculates that women are affected because of an interaction between the drugs and estrogen, which weakens bones in women. The difference may also result from women having smaller, thinner bones to begin with, so that even a loss of a little bone mass can increase the risk of fractures, Loke added.
Loke thinks that these drugs need stronger warnings about potential side effects. "The U.S. Food and Drug Administration needs to give a much stronger warning to women. And the warning should be that really these drugs should be avoided if at all possible," he said.
Dr. Lorraine Lipscombe, from the Institute for Clinical Evaluative Sciences and the University of Toronto in Canada and author of an accompanying journal editorial, thinks this study raises more concerns about the use of these drugs.
"This evidence adds to the growing concern regarding these drugs, which have also been associated with a higher risk of heart failure, and possibly heart attacks," Lipscombe said. "Because diabetes drugs are typically approved based on their effects on sugar control rather than long-term outcomes, these adverse effects have only emerged after the drugs have been on the market."
There is still not enough evidence as to the clinical benefit of these drugs -- aside from lowering blood sugar -- therefore the use of these drugs in diabetes treatment is unclear, Lipscombe said.
"Because clinical trials are designed to assess the expected effects of drugs, they often don't have enough power to detect unexpected or less common effects," Lipscombe said. "Therefore, a more standardized post-marketing surveillance process is needed to ensure that potential adverse effects are recognized as early as possible."
GlaxoSmithKline, the maker of Avandia, said this study rehashes something which is already known and reflected on its label. In addition, the company stands behinds the drug as "a safe and effective treatment for type 2 diabetes for the appropriate patient."
"The association with thiazolidinediones on bone fracture has been previously reported," said GlaxoSmithKline spokesman Jeff McLaughlin. "The labeling for rosiglitazone and pioglitazone notes the observation of an increased incidence of bone fractures in women taking the medication."
The risk of fracture should be considered in the care of patients, McLaughlin said. "In addition, GlaxoSmithKline has previously communicated this information directly to physicians via a health-care provider letter," he noted.
For more about diabetes, visit the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.
SOURCES: Yoon Loke, M.D., clinical senior lecturer, University of East Anglia, Norwich, U.K.; Lorraine Lipscombe, M.D., Institute for Clinical Evaluative Sciences and the University of Toronto; Jeff McLaughlin, spokesman, GlaxoSmithKline, Philadelphia; Dec. 10, 2008, Canadian Medical Association Journal