Two thiazoladinediones (TZDs) are currently approved for the treatment of type 2 diabetes: pioglitazone (Actos) and rosiglitazone (Avandia). Through unique actions these drugs improve insulin sensitivity, endothelial dysfunction and the dyslipidemia associated with type 2 diabetes, properties which have sparked interest in their potential antiatherogenic effects. The first large study to evaluate vascular outcomes, PROACTIVE, suggested a protective effect of pioglitazone on such outcomes. Controversy regarding that study was reviewed here.
One of the safety issues surrounding TZDs is their ability to exacerbate heart failure, a topic which was reviewed in the April 2006 issue of Cleveland Clinic Journal of Medicine. Current evidence suggests that TZDs are associated with fluid retention in some patients, and that such fluid retention may occasionally be associated with precipitation or exacerbation of heart failure. These effects appear to be due to renal and vascular effects rather than deleterious effects on the myocardium itself. The effects are reversible and may require stopping the drugs. Rather than cause heart failure outright it is more likely that the drugs induce fluid retention thereby unmasking previously asymptomatic cardiac dysfunction.
Recommendations regarding TZDs and heart failure are summarized. They should be avoided in class III and IV heart failure and used with caution in class I and II heart failure. Given the increased risk for heart failure in all diabetics, careful cardiac assessment initially and at intervals during treatment is wise.
One of the citations in the CCJM review is this excellent overview of the relationship between diabetes and heart failure published in Diabetes Care.
On a related note, macular edema has been associated with TZDs. Given that it tends to occur in those patients who develop peripheral edema it is likely a manifestation of the general tendency for fluid retention. Because the association is based on retrospective reviews and post marketing data the precise incidence is not known and cause and effect relationships are unclear.