Link to Increased Risk of Heart Problems

The thiazolidinediones (TZDs) rosiglitazone and pioglitazone are oral hypoglycemic agents used to treat type 2 diabetes and have been shown to improve glycemic control. Some research has indicated that both rosiglitazone and pioglitazone may increase the risk of congestive heart failure (CHF), and that rosiglitazone may be associated with an increased risk of acute myocardial infarction (AMI) and death. “These findings prompted a recent hearing by a U.S. Food and Drug Administration advisory panel regarding the safety of rosiglitazone; however the panel voted against removing rosiglitazone from the market because of insufficient data”, write the authors.

Lorraine L. Lipscombe, M.D., M.Sc., of the Institute for Clinical Evaluative Sciences, Toronto, and colleagues evaluated the risks of CHF, heart attack, and all-cause death associated with the use of TZDs, compared with other oral hypoglycemic agents among patients age 66 years or older with diabetes. This older patient population has often been under-represented in trials of TZDs, even though they have a high prevalence of diabetes, and may be at greater risk of medication-related harms.

The researchers analyzed data from health care databases in Ontario that included 159,026 individuals with diabetes who were treated with oral hypoglycemic agents and were followed for a median of 3.8 years, through March 2006. During this time, 7.9 percent of patients had a hospital visit for congestive heart failure, 7.9 percent had a hospital visit for a heart attack, and 19 percent died.

Compared to oral hypoglycemic agent combination therapy users, current users of TZD monotherapy had a 60 percent increased risk of congestive heart failure; had a 40 percent increased risk of heart attack; and had a 29 percent increased risk of death. These increased risks associated with TZD use appeared limited to rosiglitazone.

“Our findings argue against current labeling of TZDs that warns against use only in persons at high risk of CHF, as we did not identify any subgroup of older diabetes patients who may be protected from adverse effects of TZDs,” the authors write. “These findings provide evidence from a real-world setting and support data from clinical trials that the harms of TZDs may outweigh their benefits, even in patients without obvious baseline cardiovascular disease. Further studies are needed to better quantify the risk-benefit tradeoffs associated with TZD therapy and to explore whether the hazards associated with these agents are specific to rosiglitazone.”; Source: JAMA and Archives Journals