Issue 177 Item 1 Thiazolidinediones Linked to Congestive Heart Failure and Pulmo

Thiazolidinediones can cause or exacerbate heart failure and pulmonary oedema, and should be avoided in patients with left ventricular dysfunction or chronic renal insufficiency, according to the conclusion of a new report. Used to treat type 2 diabetes mellitus, thiazolidinediones activate peroxisome proliferator-activated receptor gamma. These drugs are known to cause idiosyncratic hepatotoxicity and fluid retention but they are rarely known to cause congestive heart failure and pulmonary edema.

To investigate this issue further, Asra Kermani, MD, and Abhimanyu Garg, MD, with the Department of Veterans Affairs Medical Center, Dallas, Texas, United States, retrospectively reviewed medical records of 6 men with type 2 diabetes, aged 66 to 78 years, treated between August 1, 2001, and May 21, 2002. Patients developed symptoms of congestive heart failure and pulmonary edema after 1 to 16 months of therapy with pioglitazone or rosiglitazone.

Of the patients, 4 had existing chronic renal insufficiency, and 1 had ischemic cardiomyopathy. In all patients, thiazolidinedione agents were discontinued when congestive heart failure and pulmonary edema developed, and diuretic agents were administered. Symptoms resolved promptly in all 6 patients.

"At our medical center during the past year, 648 patients with type 2 diabetes mellitus were treated with thiazolidinediones: 181 (28%) with pioglitazone and 467 (72%) with rosiglitazone," the researchers note. "Thus, these 6 cases represent 0.9% of patients being treated at our facility with thiazolidinedione therapy."

According to the researchers, several features of the cases support thiazolidinediones as the cause of congestive heart failure and pulmonary edema. "First, none of these patients had any acute cardiac event to explain deterioration of cardiac status. Second, 3 patients became symptomatic shortly after the dose of rosiglitazone or pioglitazone was increased. Third, all the patients experienced improvement within a few days of discontinuation of thiazolidinediones and administration of diuretics," they report.

Dr Kermani and Dr Garg conclude that thiazolidinediones "should be used with caution or avoided in patients with left ventricular dysfunction or chronic renal insufficiency."
Mayo Clin Proc 2003;78:1088-1091.

FACT: Pioglitazone Can Help Children With Type 2 Diabetes Mellitus
Pioglitazone appears to have similar pharmacokinetics in adolescents as it does in adults, suggesting it could be used in this patient population to treat type 2 diabetes. Presented a as a poster at the 32nd Annual Meeting of the American College of Clinical Pharmacology (ACCP)