Fluid retention with thiazolidinediones

Fluid retention with thiazolidinediones may be dose-dependent and a class effect (99). There is little or no evidence to suggest a direct negative effect on cardiac performance. Because the symptoms may be due to increased permeability of the microcirculation, they may respond more quickly to drug withdrawal than to diuretic therapy. 

Thiazolidinediones may produce fluid retention and edema however, the mechanism by which this occurs is not completely understood. It is known that blood volume increases approximately 10% with these agents, resulting in approximately 6% of patients developing edema. Thus, these drugs are contraindicated in situations in which an increased fluid volume is detrimental, such as heart failure. Fluid retention appears to be dose-related and increases when combined with insulin therapy. 

Cardiac effects Thiazolidinediones can cause fluid retention, which may exacerbate or lead to heart failure. Discontinue therapy if any deterioration in cardiac status occurs. Rosiglitazone and pioglitazone are not recommended in patients with NYHA Class 3 and 4 cardiac status. 

Edema Use pioglitazone and rosiglitazone with caution in patients with edema. Because thiazolidinediones can cause fluid retention, which can exacerbate or lead to CHF, use with caution in patients at risk for heart failure and monitor patients at risk for heart failure for signs and symptoms of heart failure. 

Thiazolidinediones cause fluid retention and are thus contraindicated for patients with heart failure. 

Another frequent side effect of insuhn therapy is weight gain. Some is due to increased caloric storage of glucose by insuhn, and some is due to renal sodium retention resulting in fluid retention and edema. These effects can synergize with oral agents that are often coadministered with insuhn, particularly sulfonylureas and thiazolidinediones. 

Cardiac dysfunction increases insulin resistance, suggesting that thiazolidinediones, which reduce insulin resistance might be a good choice in patients with diabetes and cardiac dysfunction. However, this case suggests that they can worsen fluid retention, perhaps by vasodilatation (57). 

Peripheral edema, which occurred in 6% of patients administered pregabalin in controlled trials (compared to 2% in the placebo arm). The peripheral edema is not a consequence of congestive heart failure, or renal or hepatic insufficiency. The thiazolidinedione class of oral hypoglycemics may increase the risk of fluid retention. In addition, because of limited data, pregabalin should be administered cautiously in patients with NYHA class III or IV cardiac status. 

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