A new study published by The BMJ adds to evidence that rosiglitazone – a drug used to treat type 2 diabetes – is associated with increased risk of heart problems, especially heart failure.
This study led by the Yale School of Public Health is the most comprehensive evaluation of the cardiovascular risk of rosiglitazone ever done. Rosiglitazone belongs to a class of drugs known as thiazolidinediones. While it was designed to control blood sugar levels in patients with type 2 diabetes, it can also increase the risk of serious heart problems. This has led to suspension of the drug in Europe and previous restrictions on its use in the United States.
“Since 2007, studies have reported conflicting findings about whether rosiglitazone increases the risk of heart attacks,” said Joshua Wallach, assistant professor at the Yale School of Public Health and the study’s lead author. “However, these studies did not
have access to the raw data, also known as individual patient level data (IPD), from clinical trials, which are more reliable when estimating a drug’s true safety profile.”
Recent efforts by GlaxoSmithKline (GSK) – rosiglitazone’s manufacturer - to make IPD available to external investigators, prompted a team of U.S. researchers to analyze the raw clinical data and clarify some of the uncertainties surrounding rosiglitazone’s cardiovascular risk.
Wallach and co-authors analyzed 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 21156 patients; the remaining trials only had summary level data available.
When the researchers analyzed 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.
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,” the researchers said.
“By including these data in research, patients, clinicians, and researchers would be able to make more informed decisions about the safety of interventions.”
“Although rosiglitazone is no longer available in Europe, and now rarely prescribed in the U.S., the rosiglitazone story is an important lesson in the value of clinical trial transparency” said Wallach. “Our study demonstrates how data-sharing platforms can be used to improve our understanding of drug safety.”
Funding for the study came from the Laura and John Arnold Foundation.
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- Haiqun Lin, MD, PhDAssociate Professor of Biostatistics