Rosiglitazone (Avandia) Linked to Fractures in Women

ROCKVILLE, Md., Feb. 21 -- The FDA informed physicians today of a report by GlaxoSmithKline of an increased number of arm, hand, and foot fractures among women taking rosiglitazone (Avandia) for newly diagnosed type 2 diabetes.

The FDA and drug company advised clinicians to carefully consider fracture risk before initiating rosiglitazone therapy.

The company said that a review of safety data from the ADOPT (A Diabetes Outcome and Progression Trial) in 4,360 patients was generally consistent with the known safety profile of the drug, but "significantly more female patients who received rosiglitazone experienced fractures than did female patients who received either metformin or glyburide."

The fracture rate was 2.74 per 100 patient years for the 645 women treated with rosiglitazone versus 1.54 per 100 patient years for the 590 women in the metformin arm and 1.29 per 100 patient year for 605 women treated with glyburide.

Although there was an increase in fractures of the humerus, hand, and foot for women taking rosiglitazone, there was no increase in hip or spine fractures, which are common sites of osteoporotic fractures in postmenopausal women.

Following the review of ADOPT safety data, the company requested an independent safety committee review of fracture data from ongoing rosiglitazone study, which was designed to evaluate cardiovascular safety of the drug.

The company said that the results of that analysis were consistent with the observations in ADOPT, but the independent safety committee "recommended that the study continue without modification." Final results of that study are expected in 2009.

Alexander R. Cobitz, M.D., Ph.D., senior director of metabolism, clinical development, and medical affairs at GlaxoSmithKline, said "the clinical significance of the findings from these two long-term trials is incomplete, and the mechanism(s) for the observed increase in fractures is uncertain."

Nonetheless, Dr. Cobitz concluded that "the risk of fracture should be considered in the care of patients, especially female patients, with type 2 diabetes mellitus who are currently being treated with rosiglitazone, or when initiation of rosiglitazone treatment is being considered."

Finally, he added that attention to assessing and maintaining bone health should be an integral part of care for all patients with diabetes.