The thiazolidinediones, rosiglitazone and pioglitazone, are peroxisome proliferator–activated receptor γ (PPAR-γ) agonists. They effectively reduce glycated hemoglobin among patients with type 2 diabetes mellitus by approximately 1 to 1.5 percentage points compared with placebo and are used as second-line treatment agents. However, rosiglitazone and pioglitazone have been associated with peripheral edema, congestive heart failure, and bone fractures.1,2 An increased risk of myocardial ischemia has been attributed to rosiglitazone.2 An increased risk of bladder cancer associated with pioglitazone is noted in the current label. Spontaneous reports of macular edema with the use of thiazolidinediones has resulted in regulatory warnings on this potential association. However, the causality remains unclear.