Rosiglitazone and risk of cancer - A meta-analysis of randomized clinical trials

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% Cl. 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% Cl 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.