The Journal of the Canadian Medical Association (CMAJ) has published the results of a systematic review and meta-analysis that aimed to quantify the fracture risk associated with glitazone therapy. There is also an accompanying editorial. This study has also reached the general media (BBC).
The analysis examined data from 10 studies involving 13,715 patients. The trials varied in duration from one to four years, collected data on fracture rates and were all double blind randomised trials. The overall risk of fracture was significantly increased by glitazone therapy with an odds ratio of 1.45 (95% confidence interval 1.18 - 1.79). When analysed separately it was found that there was no significant increase in risk among men but remained significant among women; odds ratio 2.23 (95% CI 1.65 - 3.01).
The authors note that the findings of this study have several limitations. None of the included trials were designed to measure the risk of fractures and a number of trials were excluded from the final analysis because they did not report fracture data.
Despite these limitations the rates of fractures reported were consistent with those observed in observational epidemiologic studies. The authors conclude that, "the relatively modest benefits of thiazolidinediones (glitazones) must be balanced against their significant long-term effects on bone and the cardiovascular system". In addition the authors quote the current NICE guideline recommendations that advise clinicians to "not commence or continue a thiazolidinedione (glitazone) in people who have evidence of heart failure, or who are at higher risk of fracture".
Action: This new analysis further confirms the current third line position for glitazones after metformin and sulphonylureas.