Fractures. Both Avandia and Actos appear to increase the risk of bone fractures in women—but not in men, according to a meta-analysis published in December 2008 in the Canadian Medical Association Journal. Researchers looked at 10 clinical trials involving more than 13,000 diabetics who were taking Avandia, Actos, or neither medication. The medications seemed to reduce bone density in the hips and spine of the women taking them—which researchers estimated could double the fracture risk in these women.
The research team theorized that the difference between men and women observed in this analysis may exist partially because women have small er , thin ner bones. Also, these medications may interact with estrogen in the body, resulting in weakening bones. The RECORD trial published in June also found an increased risk of fractures among women taking Avandia. The labels for Actos and Avandia both contain warnings about increased fracture risk in women.
Liver problems. Public Citizen says it has identified 14 cases of liver failure induced by Avandia, including 12 deaths, which occurred between 1997 and 2006. The group used the FDA's Adverse Event Reporting System to identify these cases. Many of the patients, according to Public Citizen, had gotten liver-function tests not long after starting Avandia, and the results were ei ther normal or mildly elevated. The people whose cases Public Citizen examined took Avandia for anywhere from half a week to more than four years . Liver toxicity has also been observed in rats, mice, and dogs that were given Avandia, according to Public Citizen's petition to the FDA. The FDA didn't respond to requests for comment about Public Citizen's analysis of liver risks. Rhyne, the GlaxoSmithKline spokesperson, says the company does not believe there is a link between Avandia and liver failure.