Takeda Pharmaceuticals, in according to FDA ( Food and Drug Administration ) has informed healthcare providers about recent safety data concerning Pioglitazone-containing products, i.e., Actos, ActoPlus Met ( Pioglitazone and Metformin ), and Duetact ( Pioglitazone and Glimepiride ). These products are used to treat type 2 diabetes mellitus.
To date, cumulative worldwide postmarketing exposure is more than 7 million patient-years for Actos and nearly 40,000 patient-years for ActoPlus Met.
Takeda has recently undertaken an analysis of its clinical trial database of Pioglitazone with a special focus on fractures, comparing patients treated with Pioglitazone or a comparator ( either placebo or active ).
The maximum duration of Pioglitazone treatment was up to 3.5 years. There were more than 81 00 patients in the Pioglitazone-treated groups and over 7400 patients in the comparator-treated groups, corresponding to just under 12,000 patient-years exposure per group.
There was no increased risk of fracture identified in men. However, there were more reports of fractures in female patients taking Pioglitazone than those taking a comparator.
The majority of fractures observed in female patients who received Pioglitazone were in the distal upper limb ( forearm, hand and wrist ) or distal lower limb ( foot, ankle, fibula and tibia ).
The fracture incidence calculated was 1.9 fractures per 1 00 patient-years in the Pioglitazone-treated group and 1. 1 fractures per 100 patient-years in the comparator-treated group. The observed excess risk of fractures for women in this data set on Pioglitazone is therefore 0.8 fractures per 100 patient-years of use.
The explanation for this finding is currently not known. It should also be noted that none of the Pioglitazone studies in the database addressed, or were designed to study, the effect on bone, but fractures were collected as adverse events. Due to the limitations of the existing data set, multiple known risk factors for fractures cannot be excluded as confounding variables. Further evaluation of these findings is ongoing.
The risk of fracture should be considered in the care of female patients with type 2 diabetes mellitus who are currently being treated with Pioglitazone, or when initiation of Pioglitazone treatment is being considered.
Source: FDA, 2007