Rosiglitazone used to treat type 2 diabetes is associated with an increased risk of heart problems, especially heart failure, shows the most comprehensive evaluation of the cardiovascular risk of rosiglitazone to date.
Rosiglitazone belongs to a class of drugs called thiazolidinediones and helps control blood sugar levels in patients with type 2 diabetes. However, the drug is currently suspended in Europe because it has been linked to the risk of serious heart problems.
Studies have produced conflicting findings on whether rosiglitazone increases the risk of heart attacks since 2007, but these studies have mostly relied on summary level data (e.g. results reported in publications and clinical trial registries) because researchers did not have access to the raw data, known as individual patient level data (IPD).
However, GlaxoSmithKline (GSK), the maker of rosiglitazone, have recently made IPD available to external investigators, prompting a team of US researchers to re-analyse the data and clarify some of the uncertainties about rosiglitazone's cardiovascular risk.
They analysed the results of more than 130 trials involving over 48,000 adult patients that compared rosiglitazone with any control for at least 24 weeks. IPD were available for 33 trials, which included 21,156 patients; the remaining trials only had summary level data available.
When the researchers analysed the IPD from trials made available by GSK, they found rosiglitazone was associated with a 33% increased risk of a composite cardiovascular event (heart attack, heart failure, cardiovascular and non-cardiovascular related death) compared with controls. This was estimated from the 274 events among 11,837 rosiglitazone patients and 219 events among 9,319 control patients, show the findings* published in The BMJ.
When examining cardiovascular events independently, the analyses of the 33 GSK trials with IPD resulted in higher estimates of the risk of heart attacks than the analyses of trials with IPD and summary level data.
These findings highlight the potential for different results derived from different data sources, and demonstrate the need for greater clinical trial transparency and data sharing to accurately assess the safety of drugs, the researchers said.
"Our study suggests that when evaluating drug safety and performing meta-analyses focused on safety, IPD might be necessary to accurately classify all adverse events. By including these data in research, patients, clinicians, and researchers would be able to make more informed decisions about the safety of interventions."
They added: "Our study highlights the need for independent evidence assessment to promote transparency and ensure confidence in approved therapeutics, and postmarket surveillance that tracks known and unknown risks and benefits."
*Wallach JD, Wang K, Zhang AD, et al. Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses. BMJ 2020; 368 :l7078