Is the evidence from clinical trials for cardiovascular risk or harm for glitazones convincing?

Thiazolidinediones (TZDs), agonists of the nuclear receptor peroxisome proliferator-activated receptor-gamma, induce the expression of many genes, including several enzymes and transporters involved in glucose and lipid metabolism. Although the efficacy of TZDs on blood glucose control in type 2 diabetes is not questionable, their cardiovascular effects have been debated, with beneficial or harmful actions suggested by different authors. This article reviews the available clinical evidence on the cardiovascular effects of TZDs, discussing possible mechanisms underlying the observed effects and suggesting some directions for future research.