Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: a retrospective cohort study

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 = 5441) were younger than control subjects (n = 28103) but more likely to have coronary artery disease or diabetes complications, receive ACE inhibitors, beta-blockers, metformin, or insulin, and have undergone HbA(1c) tests or eye exams; they also had more comorbidities and higher costs (all P < 0.05). However, TZD use was predictive of heart failure even after controlling for these variables (hazard ratio = 1.7, P < 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.