Nissen and Wolski (1) recently reported a meta-analysis of 42 clinical trials involving 27 847 patients that ignited a firestorm of controversy by concluding that treatment with rosiglitazone (Avandia, GlaxoSmithKline, Brentford, United Kingdom), a widely prescribed, peroxisome proliferator-activated receptor-γ agonist, was associated with an approximately 43% greater risk for myocardial infarction and an approximately 64% greater risk for cardiovascular death than placebo or other antidiabetic regimens. In performing their analysis, the investigators screened 116 phase 2, 3, and 4 trials. Of these, 48 met the predefined inclusion criteria of having a randomized comparator group and at least 24 weeks of drug exposure in all groups. Six of the 48 trials, with an unknown number of patients, were excluded because they did not report any cardiovascular events. Of the remaining 42 trials (38 double-blind and 4 open-label), only 10 assessed rosiglitazone monotherapy against placebo. Of the 32 trials comparing rosiglitazone with other antidiabetic therapy, 28 evaluated rosiglitazone versus placebo as an add-on therapy to sulfonylurea (n = 12), metformin (n = 10), insulin (n = 5), or usual care (n = 1), and 4 compared rosiglitazone monotherapy head-to-head with sulfonylurea or metformin. Thus, most of the trials were placebo-controlled.