Ramzi A Ajjan1, Peter J Grant. 1. University of Leeds, Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics Health and Therapeutics, Clarendon Way, Leeds LS2 9JT, UK.
Abstract
BACKGROUND: Thiazolidinediones (rosiglitazone, pioglitazone) influence insulin sensitivity and are used for the treatment of Type 2 diabetes. Rosiglitazone achieves sustained improvements in glycaemic control, whilst having pleiotropic effects on cardiovascular risk factors. However, analysis of cardiovascular outcomes has been controversial. OBJECTIVES: Review the cardiovascular safety of rosiglitazone by conducting a literature search. METHODS: We conducted a PubMed search and critically reviewed published work on cardiovascular outcome of rosiglitazone, including clinical studies and meta-analyses. RESULTS/ CONCLUSION: The meta-analysis by Nissen and Wolski suggested increased cardiovascular risk in users of rosiglitazone, but this was not supported by an interim analysis of the RECORD trial designed to evaluate this, and several other reports failed to shed conclusive light on this issue. The cardiovascular benefits of pioglitazone have also been in doubt due to the failure of the PROactive trial to reach the primary cardiovascular end points, although this study reported a significant reduction in secondary end points. All of this has left diabetes care in some disarray, with weak evidence for adverse cardiovascular effects driving the reduced use of rosiglitazone, an agent that has important sustained effects on glycaemic control.
BACKGROUND:Thiazolidinediones (rosiglitazone, pioglitazone) influence insulin sensitivity and are used for the treatment of Type 2 diabetes. Rosiglitazone achieves sustained improvements in glycaemic control, whilst having pleiotropic effects on cardiovascular risk factors. However, analysis of cardiovascular outcomes has been controversial. OBJECTIVES: Review the cardiovascular safety of rosiglitazone by conducting a literature search. METHODS: We conducted a PubMed search and critically reviewed published work on cardiovascular outcome of rosiglitazone, including clinical studies and meta-analyses. RESULTS/ CONCLUSION: The meta-analysis by Nissen and Wolski suggested increased cardiovascular risk in users of rosiglitazone, but this was not supported by an interim analysis of the RECORD trial designed to evaluate this, and several other reports failed to shed conclusive light on this issue. The cardiovascular benefits of pioglitazone have also been in doubt due to the failure of the PROactive trial to reach the primary cardiovascular end points, although this study reported a significant reduction in secondary end points. All of this has left diabetes care in some disarray, with weak evidence for adverse cardiovascular effects driving the reduced use of rosiglitazone, an agent that has important sustained effects on glycaemic control.
Authors: Paul Paolini; Daniel Pick; Jennifer Lapira; Giuseppina Sannino; Lorenza Pasqualini; Colleen Ludka; L James Sprague; Xian Zhang; Elesha A Bartolotta; Esteban Vazquez-Hidalgo; David Torres Barba; Carlos Bazan; Gary Hardiman Journal: Pharmacogenomics Date: 2014-04 Impact factor: 2.533