GlaxoSmithKline ( GSK ) has informed HealthCare Professionals of recent safety data concerning Rosiglitazone-containing products, i.e., Avandia ( Rosiglitazone maleate ) tablets, Avandamet ( Rosiglitazone maleate and Metformin hydrochloride ) tablets, and Avandaryl ( Rosiglitazone maleate and Glimepiride ) tablets.
Rosiglitazone is used in treating type 2 diabetes mellitus. To date, cumulative worldwide post marketing exposure is more than nine million patient years for Avandia, one million patient years for Avandamet, and 33,000 patient years for Avandaryl.
ADOPT ( A Diabetes Outcome and Progression Trial ) trial has been completed. ADOPT was a randomized, double-blind, parallel group study of patients with recently diagnosed type 2 diabetes mellitus whose progression of diabetes was followed for 4-6 years. The primary goal of the study was to compare glycemic control with rosiglitazone relative to Metformin and to Glyburide monotherapies in 4,360 randomized patients. The results of ADOPT were published in the New England Journal of Medicine ( NEJM ).
A review of the safety data in ADOPT was consistent, in general, with the known safety profile of Rosiglitazone. However, significantly more female patients who received Rosiglitazone experienced fractures than did female patients who received either Metformin or Glyburide.
The observed incidence of fractures for male patients in ADOPT was similar among the three treatment groups.
The majority of fractures observed in female patients who received Rosiglitazone during ADOPT were in humerus, hand, or foot.
These sites of fracture are different from those associated with post-menopausal osteoporosis ( e.g., hip or spine ).
In ADOPT, the number of female patients with a hip or spine fracture was low and similar among the three treatment groups.
At GSKs request, an independent safety committee reviewed an interim analysis of fractures in another large ongoing, long-term, controlled Rosiglitazone clinical trial.
The primary purpose of that study is to investigate cardiovascular endpoints in patients with type 2 diabetes mellitus.
The results of the preliminary analysis were reported to GSK as being consistent with the observations from ADOPT.
Source: GlaxoSmithKline, 2007