Article Summary Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure: A Consensus Statement From the American Heart Association and American Diabetes Association. Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R. Circulation 2003;108:2941-2948. Objective:In patients with diabetes, cardiovascular disease (CVD) is the main cause of mortality and is a common comorbidity. The thiazolidinedione (TZD) agents rosiglitazone and pioglitazone have been shown to reduce blood glucose levels, to decrease the risk for hypertension and hyperlipidemia, to reduce inflammatory biomarkers, and to improve endothelial function and fibrinolytic status in patients with type 2 diabetes. TZDs are indicated as monotherapy or in combination with metformin, insulin, or a sulfonylurea. Clinical trials have shown that edema can occur in patients with type 2 diabetes who are treated with the combination of TZDs plus insulin. Edema may be a symptom of congestive heart failure (CHF). Because patients with diabetes are at increased risk for such cardiovascular disorders as coronary artery disease and hypertension, the American Diabetes Association and the American Heart Association convened a workgroup to examine TZD use. Objective: To evaluate the use of TZDs in patients with preexisting heart disease, and in patients who experience weight gain or develop edema, and to develop a consensus statement based on the findings. Observations: Numerous clinical and epidemiological studies have been conducted comparing the safety and efficacy of TZDs with other antihyperglycemia agents or placebo, either alone or in combination with insulin. Compared with placebo, TZDs result in dose-related weight gain, particularly when used with insulin. TZDs, alone or combined with metformin, sulfonylurea, or insulin, are often accompanied by fluid retention and an increase in plasma volume. The reasons for fluid retention are not fully understood. An increase in plasma volume may be a result of reduced sodium excretion and an increase in sodium retention, as a synergistic action of TZD and insulin to produce arterial vasodilation. Recommendations: Clinicians are advised to examine patients with diabetes to evaluate the possibility of underlying CVD before prescribing TZDs combined with insulin. Patients should be monitored for edema and weight gain, particularly in the first 3 months of treatment. In patients with 1 or more risk factors for CHF, TZDs should be administered at the lower dosage and titrated gradually. In those with no established CVD, TZDs plus insulin may be prescribed according to the package-insert guidelines for each drug. If edema occurs but CHF does not occur during treatment, other potential causes of edema should be investigated. Conclusion: Prospective clinical trials are currently underway to determine the safety of treatment with TZDs in patients with diabetes and underlying cardiovascular disease. Until results are tabulated, clinicians should be aware of the potential risk of CHF in patients with type 2 diabetes who are treated with TZDs and insulin.