Increased Risk of Fracture Associated with Diabetes Drugs Avandia and Actos in Women

A recent study has found that the diabetes drugs Avandia (rosiglitazone) and Actos (pioglitazone) increased the risk of fractures in women. The drugs belonged to a class of drugs called the thiazolidinediones or glitazones. Glitazones work by activating the peroxisome proliferator-activated receptors( PPARs ) and thereby reducing the insulin resistance. Insulin resistance is a common feature in the type 2 diabetes mellitus. Adverse effects seem to be quite common with the thiazolidinediones. Previous studies have shown increased risk of heart failure and heart attacks with rosiglitazone. But pioglitazone seems to be free of the negative effects on the cardiovascular system. Earlier, another member of the group Troglitazone (Rezulin), was withdrawn from the market due to an increased incidence of drug-induced hepatitis.

Dr. Sonal Singh, an assistant professor at the Wake Forest University Baptist Medical Center did a meta-analysis of data from previous clinical studies. The study revealed that use to the glitazones doubled the risk of fractures in women. The most common fractures suffered by women were in their arms and legs, Dr. Singh said. But there was no statistically significant increase in the incidence of bone fractures among men. The data was collected from 10 randomised controlled studies involving 13715 patients and 2 observational studies involving 31,679 patients. The bone mineral density of women exposed to the above drugs was significantly low at the lumbar spine. One possible explanation for these findings is that women are affected because of an interaction between the drugs and estrogen. Also, women have smaller, thinner bones compared to men and hence a little loss of bone density predisposes them to fractures. The researchers concluded that the relatively modest benefits of rosiglitazone and pioglitazone should be balanced against their long term effects on the bone and the cardiovascular system and that clinicians should reconsider their use in women with type 2 diabetes mellitus.

Last year, the interim findings form a group of researchers affliated with Newcastle Diabetes Centre and Newcastle University, Newcastle upon Tyne, United Kingdom and published in the New England Journal of Medicine found that rosiglitazone was associated with an increased risk of heart failure. The data analysis was inconclusive regarding the effect of rosiglitazone on the overall risk of hospitalization or death from cardiovascular causes. A study published in the Journal of American Medical Association concluded that among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality. The higher cost and the adverse effects of the glitazones makes them less appealing for the initial first line of therapy for diabetes mellitus. The initiation of Rosiglitazone and Pioglitazone is contraindicated in patients with New York Heart Association class III or IV Heart Failure, and cautions exist for their use in any patient with heart failure. The prescription of glitazones for women should be scrutinized in context of its doubling the risk of fractures.


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