Moreover, the study raises concern that the new drug -- dubbed Pargluva by Bristol-Myers Squibb and Merck -- also raises cancer risk.
The new study, published today online by The Journal of the American Medical Association, uses the same data reviewed by the FDA panel and FDA staff. Yet it comes to a starkly different conclusion than the panel did in its 8-1 vote advising FDA approval of Pargluva.
The new analysis of the data comes from researchers at The Cleveland Clinic. They report that Pargluva-treated patients had nearly a threefold greater risk of death, heart attack, stroke, and heart failure.
"These findings are particularly concerning because the significant excess of adverse events was observed after only limited drug exposure ranging from 24 to 104 weeks," Steve E. Nissen, MD, and colleagues report. "Real-world exposure would likely substantially amplify the risk. Taken as a whole, these data demonstrate that [Pargluva], if approved by the FDA, would constitute an unacceptable patient hazard."
Heart Risk + Cancer Risk?
A JAMA editorial released alongside the Nissen report raises another disturbing question about Pargluva safety. Editorialist James M. Brophy, MD, PhD, of McGill University in Montreal, says patients who took Pargluva were more likely to get cancer than patients who took inactive pills (placebo).
Brophy notes that the drug's manufacturers told the FDA expert panel that cancer rates were not increased in patients treated with Pargluva. That's true when looking at statistics that researchers use to determine if something is clinically meaningful.
But Brophy notes that a worrisome trend emerged showing that Pargluva patients may be three times as likely to develop cancer. He notes that this association could grow significantly with more widespread use.
"A very large increase in cancer risk cannot be excluded with the limited available data," Brophy writes.
Pargluva Was Eagerly Awaited
Diabetes experts have had high hopes for Pargluva. This dual-action drug is the first of its kind to attack two distinct problems seen in people with diabetes -- high blood sugar and high cholesterol. Similar drugs, Actos and Avandia, primarily tackle only high blood sugar, according to the researchers.
Because diabetes is a serious, life-threatening disease, Brophy says Pargluva might yet prove to be a valuable drug. But he joins Nissen and colleagues in calling for a large, premarketing safety trial.
In a statement released today, Bristol-Myers Squibb spokesman David M. Rosen says both Bristol-Myers Squibb and Merck "are eager to begin discussions with the FDA to address more fully the cardiovascular safety profile of [Pargluva] and to determine what additional information may be necessary."