Rosiglitazone and Risk of Cancer

OBJECTIVE Despite experimental data suggesting a protective effect of peroxisome proliferator-activated receptor-gamma agonists with respect to malignancies, results of available epidemiological studies on the incidence of cancer in rosiglitazone-treated patients are not univocal. The aim of this meta-analysis of randomized clinical trials is to assess the effect of rosiglitazone on the incidence of cancer. RESEARCH DESIGN AND METHODS Randomized clinical trials of rosiglitazone with duration of >24 weeks were retrieved through Medline and from the GlaxoSmithKline Web site, which reports main results of all trials sponsored by GlaxoSmithKline; incident malignancies were retrieved from the summary of serious adverse events. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% CI. Considering differences in the duration of follow-up among treatment arms in some of the trials, we also calculated the incidence of cancer in rosiglitazone and control groups. RESULTS Eighty trials, enrolling 16,332 and 12,522 patients in the rosiglitazone and comparator groups, respectively, were retrieved. Rosiglitazone was not associated with a significant modification of the risk of cancer (OR 0.91 [95% CI 0.71-1.16], P = 0.44). The incidence of malignancies was significantly lower in rosiglitazone-treated patients than in control groups (0.23 [0.19-0.26] vs. 0.44 [0.34-0.58] cases/100 patient-years; P < 0.05). CONCLUSIONS The use of rosiglitazone appears to be safe in terms of incidence of cancer, whereas its possible protective effect needs to be further investigated.