Pioglitazone initiation and subsequent hospitalization for congestive heart failure

Thiazolidinediones (TZD) have been associated with an expansion in plasma volume and the development of peripheral oedema. A recent study reported an association between the use of TZDs and development of congestive heart failure (CHF). The objective of this study was to determine if short-term use of pioglitazone, a TZD, is associated with increased risk of admission to hospital because of CHF in a well-characterized, community-based cohort of Type 2 diabetic patients without prevalent CHF.

A cohort study of all patients in the Kaiser Permanente Medical Care Program with Type 2 diabetes (Kaiser Permanente Northern California Diabetes Registry) who initiated any diabetes pharmacotherapy (n = 23 440) between October 1999 and November 2001. Only patients initiating single new therapies ('new users') were included to reduce confounding and create mutually exclusive exposure groups. We constructed Cox proportional hazards models (with sulphonylureas initiators specified as the reference group) to evaluate the impact of initiating new diabetes therapies on time-to-incident admission to hospital because of CHF, defined by primary hospital discharge diagnosis.

Patients initiated pioglitazone (15.2%), sulphonylureas (25.3%), metformin (50.9%), and insulin (8.6%) alone, or as additions to pre-existing or maintained therapies. Three hundred and twenty admissions for CHF were observed during the follow-up (mean 10.2 months) after drug initiation. Relative to patients initiating sulphonylureas, there were no significant increases in the incidence of hospitalization for CHF in those initiating pioglitazone [hazard ratio (HR) = 1.28; 95% confidence interval (CI): 0.85-1.92] after adjusting for demographic, behavioural and clinical factors. There was a significantly higher incidence among those initiating insulin (HR = 1.56; 95% CI: 1.00-2.45) and lower incidence among those initiating metformin (HR = 0.70; 95% CI: 0.49-0.99).

This study of patients with Type 2 diabetes failed to find evidence that short-term pioglitazone use was associated with an elevated risk of hospitalization for CHF relative to the standard, first-line diabetes therapy.