Patients with diabetes, especially women, who take thiazolidinediones, which include commonly prescribed drugs such as Avandia and Actos, may have an increased risk of developing cancer, according to a new report.

“There is more to these drugs than first meets the eye,” Dr. Maria E. Ramos-Nino from the University of Vermont, Burlington, told Reuters Health. “The long-term consequences and benefits are not understood.”

Ramos-Nino and colleagues investigated the association of thiazolidinediones and cancer prevalence among nearly 9,000 diabetic patients participating in a large database. A randomly selected sample of 1,003 of these participants were interviewed about personal and clinical characteristics, including any history of malignancy. The findings are published in the current issue of BMC Medicine.

After factoring in the potential effects of other risk factors, the investigators found that the use of any thiazolidinedione was associated with a 59-percent increased risk of cancer. The use of Avandia (rosiglitazone) increased the malignancy risk by 89 percent, whereas the increased risk associated with Actos (pioglitazone) was not statistically significant.

“We are not aware of a convincing explanation or previous results to support the finding in this study of an association with cancer for rosiglitazone, but not for pioglitazone,” the researchers write. Both drugs are thought to work through the same mechanism and have a similar potency. Therefore, another mechanism may account for the association.

Women taking thiazolidinediones were more than twice as likely to have cancer as women not taking thiazolidinediones, the researchers note, but the association was not statistically significant in men.

Conversely, the use of sulfonylurea by women was associated with a 51-percent lower risk of cancer, the report indicates.

“The gender-dependent observation is difficult to explain,” the team notes. “We do not know which specific tumors are increased in the thiazolidinedione users in this population.”

The authors acknowledge that the study has several limitations, including its cross-sectional design, lack of confirmation of cancer, and the absence of information on the temporal relation between thiazolidinedione use and cancer.

“Our data do not provide strong evidence to change practice at this time,” Ramos-Nino stressed. “They are disturbing, to be sure, but require further investigation before clinical decisions should be changed.”

SOURCE: BMC Medicine, June 21, 2007.