Safety watchdog flags GLP-1 drugs for pancreatitis reports to FDA

Two months ago, a study published in the Journal of the American Medical Association raised some new questions about cancer risks linked with some big diabetes drugs. One month ago, the FDA said it was reviewing data on the two drugs flagged in that study--Merck's ($MRK) Januvia, and Bristol-Myers Squibb ($BMY) and AstraZeneca's ($AZN) Byetta--as well as other drugs, including Novo Nordisk's ($NVO) blockbuster Victoza. Now, as Pharmalot reports, a safety watchdog group has analyzed the FDA's adverse event data, finding more reports of pancreatitis and pancreatic cancer for these drugs compared with older treatments.

The Institute for Safe Medication Practices (ISMP) analysis found that reports of these maladies were about 25 times higher for the GLP-1 class. As individual drugs, Januvia, a DPP-4 inhibitor, along with GLP-1 drugs Byetta and Victoza, were found to have the greatest odds of pancreatitis reports. The odds were lower, but still above those for older treatments, for DPP-4 inhibitors Eli Lilly ($LLY) and Boehringer Ingelheim's Tradjenta/Trajenta; and Bristol-Myers Squibb and AstraZeneca's Onglyza.

These numbers don't necessarily mean that there's a causal relationship between the drugs and the adverse event reports. The FDA database depends on reports from doctors, patients and companies. Some cases never make it into the database because they go unreported. And reports themselves can be misleading, because there's no way of knowing whether a particular case actually stemmed from drug treatment or simply coincided with it. In the case of the GLP-1 and DPP-4 drugs, they're often added to metformin as patients' blood-sugar control flags, so the people who use them may already be at higher risk of pancreatitis.

Plus, because the reports are voluntary, one can't lean too much on them in comparisons among different drug brands. Still, higher numbers are cause for concern, and the FDA often investigates drugs based on them.

But as Pharmalot reports, the ISMP is sufficiently concerned to call for follow-up study. "I think the future of the whole class is in question," the ISMP's Thomas Moore told the blog. "[I]f results are confirmed in a broader patient population, it raises questions about the entire class of drugs."

Meanwhile, since the JAMA study hit, drugmakers and doctors poked holes in the data. Bristol-Myers and Merck have both defended their drugs. Both already carry label warnings about pancreatitis cases. We'll have to wait and see what the FDA says when its review is complete.

- read the Pharmalot post