Pioglitazone as well as rosiglitazone increases fractures in women
Pioglitazone (Actos; Takeda) increases fracture risks in women with diabetes, a new analysis of clinical trial data reported by the US Food and Drug Administration indicates.
Earlier this month, the FDA
published a safety alert together with an
analysis by Takeda of its clinical trials database, comparing patients
treated with pioglitazone (over 8,100 patients) with a comparator (either
placebo or active agent; over 7,400 patients). The analysis showed an
increased risk of fractures in female patients taking pioglitazone compared
with those taking a comparator.
The sites of the fractures are different from those associated with post-menopausal
osteoporosis (eg, hip or spine). Most of the excess fractures were in
the forearm, hand and wrist or foot, ankle, fibula and tibia. The fracture
incidence was 1.9 fractures per 100 patient-years in the pioglitazone-treated
group and 1.1 fractures per 100 patient-years in the comparator-treated
group. The findings confirm the side effect to be a feature of all the
licensed thiazolidinediones.
In December 2006, the ADOPT study (a diabetes outcome progression trial)
revealed this side effect with rosiglitazone (Avandia; GlaxoSmithKline).
ADOPT aimed to compare glycaemic control with rosiglitazone relative
to metformin and to glibenclamide monotherapies in 4,360 patients. Rury
Holman, professor of diabetic medicine at the diabetes trials unit, University
of Oxford, and an investigator on the ADOPT study, said that while it
would be premature to take patients off these agents, health care professionals
should be vigilant and consider the risk for the individual patient.
Steven Kahn, lead investigator on ADOPT, warns that, while bone health
strategies may be prudent in at-risk patients, at this time it is not
known whether pharmacological approaches that can be taken to prevent
osteoporotic fractures will be effective in preventing fractures with
thiazolidinediones.
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The
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