Use of Thiazolidinediones and Risk of Heart Failure in People With Type 2 Diabetes

Abstract

OBJECTIVE -To compare the incidence of heart failure in individuals with type 2 diabetes receiving thiazolidinediones (TZDs) versus other oral antihyperglycemic agents.RESEARCH DESIGN AND METHODS -We conducted a retrospective cohort study using a health insurance claims database. The study sample included patients with type 2 diabetes who received an oral antihyperglycemic agent between January 1995 and March 2001. Those with any claims for TZDs were designated "exposed," and each was compared with five randomly selected unexposed patients. Those with diagnoses of heart failure or who received digoxin or a diuretic in the year before their index date were excluded. The primary measure of interest was incidence of heart failure, which was defined as a hospitalization or outpatient visit with a diagnosis of heart failure.RESULTS -TZD patients (n ϭ 5,441) were younger than control subjects (n ϭ 28,103) but more likely to have coronary artery disease or diabetes complications, receive ACE inhibitors, ␤-blockers, metformin, or insulin, and have undergone HbA 1c tests or eye exams; they also had more comorbidities and higher costs (all P Ͻ 0.05). However, TZD use was predictive of heart failure even after controlling for these variables (hazard ratio ϭ 1.7, P Ͻ 0.001). Adjusted incidence of heart failure at 40 months was 8.2% for TZD patients and 5.3% for control subjects.CONCLUSIONS -The results of this observational study suggest that TZDs may increase the risk of heart failure. Physicians should use TZDs with caution in patients with heart failure, remain vigilant for manifestations of heart failure in those receiving these drugs (especially patients with cardiovasculopathy), and consider alternate therapies for patients who develop symptoms of heart failure, such as shortness of breath.

Thiazolidinediones

“…A higher risk of heart failure has been reported in some studies (25), whereas others have actually suggested a reduced risk of heart failure in glitazone-treated patients (26). A recent analysis demonstrated reduced mortality in patients with a prior history of heart failure who were treated with glitazones (27).…”

Observational studies of the association between glucose-lowering medications and cardiovascular outcomes: addressing methodological limitations

“…It has been shown that claims data can identify cardiovascular endpoints with very high specificity, resulting in relatively small potential for bias associated with misclassification of the outcome [124][125][126][127][128]. Among the evaluated literature, few explorative analyses assessed the potential effect of outcome misclassification on the study estimates [68,70].…”

“…Subjects will be balanced with regard to all baseline covariates and follow-up will start after the accumulation of pre-specified levels of dispensed dose or treatment duration. Few studies included analyses assessing the effect of cumulative exposure to glucose-lowering agents [11,12,19,37,45,47,49,61,68].…”

Fat poetry: a kingdom for PPARγ

“…The latter, which can be explained by PPARg stimulation of ENaC-mediated renal salt absorption [218], might be the cause of an increased incidence of congestive heart failure [219], an outcome also observed in rats where rosiglitazone treatment is associated with increased post-myocardial infarction mortality [220]. However, this issue is still under debate as the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) showed recently that treatment of type 2 diabetic patients with pioglitazone, another TZD drug, improved their cardiovascular outcome [113].…”