Background: Thiazolidinediones (TZDs) are used for the therapy of type II diabetes. Several warning on their cardiovascular (CV) and fracture risks have been raised. Their benefit/risk profile is therefore still uncertain. Objectives: To evaluate the safety profile of TZDs, in particular on the risk of CV events and bone fractures, on the basis of FDA Adverse Event Reporting System (AERS). Methods: Association between drugs and ADRs was analysed by case/non case method. Cases were ADR reports with TZDs as suspected drug and non-cases were all same reactions induced by other drugs. Association between TZDs and ADRs were calculated by the ADR reporting odds ratio (ROR). Safety data for TZDs, and for individual drugs, were compared against other anti-diabetic drugs. Results: Evidence of disproportionality were observed for CV ADRs compared to other anti-diabetics, in particular for cardiac failure congestive (ROR 6.11, CI 95%5.68–6.56 vs 0.66, 0.60–0.73) and myocardial infarction (2.46, 2.33–2.59 vs 0.32, 0.30–0.34). Rosiglitazone showed the highest ROR for cardiac ADRs, whereas pioglitazone only for cardiac failure. Concerning fractures, TZDs showed significant RORs compared to other anti-diabetic drugs, e.g. radius (3.64, 2.15–6.06 vs 0.47, 0.24–0.91), foot (2.16, 1.55–2.99 vs 0.98, 77–1.24), and humerus (2.76, 1.82– 4.15 vs 0.28, 0.15–0.51). Among TZDs, pioglitazone achieved significant RORs for ulna, radius, fibula, humerus, tibia and ankle fractures, whereas rosiglitazone was significantly associated to foot, humerus and radius fractures. Conclusions: The frequency of CV reactions and fractures occurrences were significantly higher for TZDs in comparison to other anti-diabetic drugs. Rosiglitazone showed a significant disproportionality for CV ADRs whereas pioglitazone for multiple site fractures. These differences should be considered when rosiglitazone or pioglitazone are prescribed.
Safety profile of thiazolidinediones on the basis of the FDA-AERS database: cardiovascular and bone fracture risks for rosiglitazone and pioglitazone / Motola D.; Poluzzi E.; Marra A.; Biagi C.; Piccinni C.; Montanaro N.. - In: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY. - ISSN 1053-8569. - STAMPA. - 19:Supplement 1(2010), pp. 300.129-300.129. (Intervento presentato al convegno 26th ICPE: International Conference on Pharmacoepidemiology & Therapeutic Risk Management tenutosi a Brighton, England, UK nel August 19-22, 2010).
Safety profile of thiazolidinediones on the basis of the FDA-AERS database: cardiovascular and bone fracture risks for rosiglitazone and pioglitazone
MOTOLA, DOMENICO;POLUZZI, ELISABETTA;BIAGI, CHIARA;PICCINNI, CARLO;MONTANARO, NICOLA
2010
Abstract
Background: Thiazolidinediones (TZDs) are used for the therapy of type II diabetes. Several warning on their cardiovascular (CV) and fracture risks have been raised. Their benefit/risk profile is therefore still uncertain. Objectives: To evaluate the safety profile of TZDs, in particular on the risk of CV events and bone fractures, on the basis of FDA Adverse Event Reporting System (AERS). Methods: Association between drugs and ADRs was analysed by case/non case method. Cases were ADR reports with TZDs as suspected drug and non-cases were all same reactions induced by other drugs. Association between TZDs and ADRs were calculated by the ADR reporting odds ratio (ROR). Safety data for TZDs, and for individual drugs, were compared against other anti-diabetic drugs. Results: Evidence of disproportionality were observed for CV ADRs compared to other anti-diabetics, in particular for cardiac failure congestive (ROR 6.11, CI 95%5.68–6.56 vs 0.66, 0.60–0.73) and myocardial infarction (2.46, 2.33–2.59 vs 0.32, 0.30–0.34). Rosiglitazone showed the highest ROR for cardiac ADRs, whereas pioglitazone only for cardiac failure. Concerning fractures, TZDs showed significant RORs compared to other anti-diabetic drugs, e.g. radius (3.64, 2.15–6.06 vs 0.47, 0.24–0.91), foot (2.16, 1.55–2.99 vs 0.98, 77–1.24), and humerus (2.76, 1.82– 4.15 vs 0.28, 0.15–0.51). Among TZDs, pioglitazone achieved significant RORs for ulna, radius, fibula, humerus, tibia and ankle fractures, whereas rosiglitazone was significantly associated to foot, humerus and radius fractures. Conclusions: The frequency of CV reactions and fractures occurrences were significantly higher for TZDs in comparison to other anti-diabetic drugs. Rosiglitazone showed a significant disproportionality for CV ADRs whereas pioglitazone for multiple site fractures. These differences should be considered when rosiglitazone or pioglitazone are prescribed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
