Regulators Have Called Off the Dogs, but Concern Over Januvia Lingers

Washington, DCThe US Food and Drug Administration (FDA) appeared quick to follow the lead of the European Medicines Agency (EMA) when it concluded there was insufficient data to warrant label changes to Merck’s Januvia and other GLP-1 drugs over concerns for pancreatitis and pancreatic cancer, including Januvia pancreatic cancer. The American Diabetes Association (ADA) has taken a similar stance, noting that there is not enough evidence to warrant changes in treatment protocols for patients with type 2 diabetes.

But have the agencies breathed a sigh of relief too soon? And are such assurances akin to placing a consumer Band-Aid over a gaping wound?

Prior to the deceleration of concern on the part of the drug regulators, there had been plenty of warnings from various health watchdog groups and consumer advocates over Januvia side effects and similar drugs in the class.

For example, the Institute for Safe Medicine Practices (ISMP) examined 1,723 serious adverse events reported to the FDA between July 1, 2011 and June 30, 2012 for all five of the GLP-1 drugs, which mimic a hormone called GLP-1 to stimulate natural insulin production. ISMP found 831 cases of pancreatitis; 105 cases of pancreatic cancer; 32 cases of thyroid cancer and 101 cases indicating a hypersensitivity reaction.

Thomas Moore, senior scientist for drug safety and policy with the ISMP, noted that while further study was necessary, “I think the future of the whole class is in question. If results are confirmed in a broader patient population, it raises questions about the entire class of drugs.”

The analysis compared adverse reactions reported to the FDA against a control group consisting of older, more traditional drugs such as metformin. The analysis found that GLP-1 drugs including Januvia carried odds that were 25 times higher for the potential to develop Januvia cancer.

Another study on Januvia and cancer (and other GLP-1 drugs) first published in the journal Diabetes examined the pancreases of 20 deceased human organ donors with type 2 diabetes. Eight had been treated for at least one year with incretin therapy (GLP-1) while the remaining 12 received other therapies that did not include incretin-based drugs. The researchers also evaluated 14 pancreases from non-diabetic controls of a similar age.

“Pancreas of the individuals who had been on incretin therapy were larger than the organs from those who had been on other types of diabetes therapies, and was associated with increased cellular proliferation. Pancreas from incretin treated individuals also had an increase of pancreas dysplasia, an abnormal form of cell proliferation that is a risk factor for pancreatic cancer,” according to a statement issued by the researchers.

Regulators and the pharmaceutical industry have dismissed a study that noted consumer advocacy group Public Citizen referenced as “brilliantly-designed and executed.” Drs. Alexandra Butler and Peter Butler, of whom we have referenced before, undertook the study with their colleagues in concert with UCLA in California and the University of Florida.

In a statement released earlier this year, the Director of Health Research Group for Public Citizen was bullish on the study and the concerns over Januvia and other GLP-1 drugs. “It is clear that all of the drugs in this family are associated with an increased risk of pancreatic cancer and it is likely that they will all have to be removed from the market,” Dr. Sidney Wolfe says in a statement release this past spring, prior to the vetting of Januvia by the EMA and FDA.

“The idea of putting a warning label about pancreatic cancer on drugs that have no unique benefit for diabetics but which have increasing evidence of the risk for pancreatic cancer - instead of banning the drugs altogether - would be an extraordinarily reckless approach for the FDA to initiate.”

As it turns out, the FDA isn’t even doing that. Pending further study, the FDA has aligned with the EMA and, with the blessing of the American Diabetes Association, is simply maintaining the status quo. Pharmaceutical companies could not be happier…