Rosiglitazone Linked to Fracture Risk in Women

Yael Waknine

Disclosures

February 21, 2007

February 21, 2007 — The risk for upper arm, hand, or foot fractures may be increased in women receiving rosiglitazone maleate vs metformin HCl or glyburide for type 2 diabetes mellitus, according to a warning from the US Food and Drug Administration (FDA) and GlaxoSmithKline (GSK).

An alert was sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.

The warning was based on data from A Diabetes Outcome Progression Trial (ADOPT), which followed 4360 drug-naive, newly diagnosed patients for 4 to 6 years. The study's primary end point was to compare glycemic control achieved by rosiglitazone, metformin, and glyburide monotherapy.

Although results showed that rosiglitazone was significantly more effective than either metformin or glyburide in reducing the risk for therapeutic failure, women receiving the drug were significantly more likely than their metformin- and glyburide-treated counterparts to experience fractures of the humerus (rate per 100 patient-years, 0.23 for rosiglitazone vs 0 for metformin and 0 glyburide), hand (0.37 vs 0.21 and 0.06), or foot (1.01 vs 0.36 and 0.25).

These fractures differ from those commonly associated with postmenopausal osteoporosis (eg, hip or spine); hip fracture rates in the rosiglitazone vs metformin and glyburide groups were 0.09 vs 0.10 and 0, and spine fracture rates were 0.05 vs 0.05 and 0.06. Fracture rates for men were similar among the 3 groups (1.16 vs 0.98 and 1.07).

Moreover, a company-requested independent interim analysis of fracture rates in a large, ongoing, long-term rosiglitazone trial has provided further evidence for these observations. Final results of this study, which was initiated to evaluate cardiovascular end points in patients with type 2 diabetes, are expected to be available in 2009.

GSK notes that the clinical significance of these findings remains unclear, and the mechanism for the observed increase in fractures uncertain; further evaluations are ongoing.

In the interim, the risk for fracture should be considered when initiating or continuing rosiglitazone therapy, particularly in women. As with all type 2 diabetic patients, assessment and maintenance of bone health according to current standards of care is advised.

Rosiglitazone is currently marketed as a single drug ( Avandia), in combination with metformin HCl ( Avandamet), and with glimepiride ( Avandaryl, all made by GSK) for use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. Additional information regarding use of rosiglitazone may be obtained by contacting the company at 1-888-825-5249.

Healthcare professionals are encouraged to report rosiglitazone-related adverse events to the company at the telephone number above. This information may also be communicated to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch , or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

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