GlaxoSmithKline (GSK) (PHILADELPHIA, Pennsylvania) informs healthcare providers of recent safety data concerning rosiglitazone-containing products, ie, Avandia® (rosiglitazone maleate) tablets, Avandamet® (rosiglitazone maleate and metformin hydrochloride) tablets, and Avandarylâ„¢ (rosiglitazone maleate and glimepiride) tablets. These products are used in treating type 2 diabetes mellitus (T2DM). The review of the safety data found that significantly more female patients who received rosiglitazone experienced fractures than did female patients who received either metformin or glyburide. The majority of fractures observed in female patients who received rosiglitazone during (A Diabetes Outcome Progression Trial) ADOPT were in the upper arm (humerus), hand, or foot. These sites of fracture are different from those associated with postmenopausal osteoporosis (eg, hip or spine).

In ADOPT, the hip fracture rate in female patients was low. The observed incidence of fractures for male patients was similar among the three treatment groups. The fracture rate was 2.74 per 100 patient years for women treated with rosiglitazone versus 1.54 per 100 patient years for women in the metformin treatment group and 1.29 per 100 patient years for women treated with glyburide. To date, cumulative worldwide postmarketing exposure is more than 9 million patient years for Avandia, 1 million patient years for Avandamet, and 33,000 patient years for Avandaryl.

The safety data were generated from ADOPT, a randomized, double-blind, parallel group study of 4360 patients with recently diagnosed T2DM whose progression of diabetes was followed for 4 to 6 years. The primary goal of the study was to compare glycemic control with rosiglitazone relative to metformin and to glyburide monotherapies.

At GSK's request, an independent safety committee reviewed an interim analysis of fractures in another large, ongoing, long-term controlled rosiglitazone clinical trial. The results of the preliminary analysis were reported to GSK as being consistent with the observations from ADOPT.

Clinical significance of the findings from these two long-term trials remains unclear, and the mechanism(s) for the observed increase in fractures is uncertain; further evaluation is ongoing. GSK believes the risk of fracture should be considered in the care of patients, especially female patients, with T2DM who are currently being treated with rosiglitazone, or when initiation of rosiglitazone treatment is being considered. In these patients, as with all patients with T2DM, attention should be given to assessing and maintaining bone health according to current standards of care.

—A. Techman

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