A new study of Avandia, a controversial drug that changed the way FDA does business, shows that the researchers who first found a link between the diabetes drug and heart attacks and death were probably right.
The new study of rosiglitazone, sold by GlaxoSmithKline as Avandia, published in the BMJ shows that when individual patient-level data are examined in isolation, the type 2 diabetes drug is associated with a 33% increased risk of heart attack, heart failure, and death from cardiovascular disease or other causes. Heart failure stood out as being particularly more common among patients who took Avandia compared with those who took a control across the 33 studies where patient-level data were available.
Avandia is among the most controversial drugs in history. Approved in 1999, its sales topped $2.5 billion a year until 2007 study results reported in the New England Journal of Medicine by Cleveland Clinic's Steven Nissen and Kathy Wolski showed an association between the type 2 diabetes treatment and heart attacks and early death. Lawsuits and sales restrictions followed, although later studies found came to differing conclusions. By the time the patent expired in 2012, sales of Avandia had fallen to less than half their peak level.
But the drug’s lasting legacy was the 2008 FDA guidance that changed the way diabetes and cardiovascular drugs are evaluated.
After that, manufacturers had to do more than show a diabetes drug could lower blood sugar. They also had to invest in large, expensive cardiovascular outcomes trials that are designed to prove that a new drug is not associated with heart attack and strokes.
Over the next decade, the new wave of diabetes treatments were subject to these trial, especially SGLT2 inhibitors, a class that includes Invokana, Farxiga, and Jardiance. In the process, scientists learned not only were these drugs safe, but patients who took them might be less likely to have heart attacks or end up in the hospital with heart failure. They appear to all-purpose weapons against diabetes, heart failure, renal decline, and even, perhaps, obesity. Another class of drugs called GLP-1 receptor agonists, which includes Trulicity, Byetta, and Victoza, also appear to have some protective effects.
The BMJ findings stem from a decision by GSK to make patient-level data from trials available; patient-level data may be more revealing of adverse events than registry data. The full study involved more than 130 trials and 48,000 patients, with each trial comparing Avandia with a control for at least 24 weeks. When results for trials without individual patient data were included, the differences were not as robust.
The authors, from Yale, say the findings show why sharing patient-level data from multiple studies matters when studying whether a drug is safe.
"By including these data in research, patients, clinicians, and researchers would be able to make more informed decisions about the safety of interventions,” write Joshua D. Wallach and his colleagues.