Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database

Type 2 diabetic patients were identified from the French Database of PharmacoVigilance (FPVD) between 2002 and 2006. We investigated ADR related to TZD, focusing on 4 ADR: edema, heart failure, myocardial infarction and hepatitis corresponding to specific WHO-ART terms.Among a total of 99,284 adult patients in the FPVD, 2295 reports concerned type 2 diabetic patients (2.3% of the whole database), with 161 (7%) exposed to TZDs. The frequency of edema and cardiac failure was significantly higher with TZDs than in other patients (18% and 7.4% versus 0.8% and 0.1% respectively, p < 0.001) whereas the frequency of hepatitis was similar (5.9% versus 4%, NS). A multiple logistic regression model taking into account potential confounding factors (age, gender, drug exposure and co-morbidities) found that TZD exposure remained associated with heart failure and edema, but not with hepatitis or myocardial infarction.Thiazolidinediones exposure is associated with an increased risk of edema and heart failure in patients with type 2 diabetes even when recommendations for use are respected. In contrast, the risk of hepatic reactions and myocardial infarction with this class of drugs seems to be similar to other hypoglycemic agents.Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor (PPAR) agonists which regulate transcription of genes encoding proteins involved in glucose and lipid metabolism. Troglitazone, the first agent of this class, caused serious liver toxicity leading to its withdrawal in 2000, less than 3 years after its marketing [1]. The use of the 2 other TZDs, rosiglitazone (RGZ) and pioglitazone (PGZ), has sharply increased during the last few years. These 2 drugs seem to present a lower risk of hepatotoxicity than troglitazone [2].TZDs could also induce adverse drug reactions (ADRs) related to the cardiovascular system including edema and heart failure [3,4]. Edema is more frequent when the TZD is used in combination therapy and its incidence is h