For the past month, a group of diabetes drugs have been under a microscope over concerns they cause not only pancreatitis, but also pre-cancerous cellular changes. Pancreatitis is actually not a new concern; the FDA issued alerts twice in recent years for two widely used drugs - Byetta, which is now sold by Bristol-Myers Squibb, and Januvia, a Merck treatment. But concerns about the pre-cancerous changes only surfaced two weeks ago (back stories here and here).
That's when the FDA referenced an unpublished study indicating such a link when announcing the risks would be studied (read this). Now, the European Medicines Agency is also investigating the drugs (look here) and study has been published and a consumer watchdog is arguing that issuing new warnings on product labeling would be insufficient. Instead, Public Citizen Health Research Group plans to ask the FDA to ban the drugs, which are called incretin mimetics, altogether.
"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," the consumer group says.
The drugs, which mimic a hormone called GLP-1 to stimulate natural insulin production, also include Victoza, which is sold by Novo Nordisk (NOVO); Onglyza, which is marketed by Bristol-Myers (BMY) and AstraZeneca (AZN); and Tradjenta, which is marketed by Eli Lilly (LLY) and Boehringer Ingelheim, as well as Janumet, another drug sold by Merck (MRK). Public Citizen previously asked the FDA to ban Victoza over ties to pancreatitis.
The study, which was published in Diabetes, found that in humans, the drugs caused “marked” cell proliferation and damage, and displayed a potential for eventually transforming into cancer. The researchers examined the pancreas of 20 deceased human organ donors with type 2 diabetes. Eight had been treated for at least one year with incretin therapy 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. They noted that, of the eight donors who were on incretin therapy, seven had been taking Januvia and one had been on Byetta (here is the abstract).
"The present studies are only from a small number of individuals, and while the findings do raise concerns, it will be important that other approaches are now used in a larger group of living individuals to further investigate these findings," says Peter Butler, director of UCLA's Hillblom Islet Research Center and chief of the endocrinology, diabetes and hypertension unit and one of the authors, says in a statement.
A spokesman for Bristol-Myers, which has a diabetes venture with AstraZeneca, writes us that the drugmakers “are confident in the benefit-risk profile of Byetta, Bydureon, Onglyza and Kombiglyze XR as demonstrated by extensive clinical trial data and safety surveillance data.
And a Merck spokesman writes us that “we disagree with the authors’ conclusions. Definitive conclusions cannot be drawn from this small study. In our extensive evaluation of data, we have seen no compelling evidence of a causal relationship between the use of (Januvia) and pancreatitis or pancreatic cancer. We are confident in the safety profile…
“It is also important to note that there are inherent limitations to case-control studies. For example, in this small case-control study, there are meaningful differences noted in the average age, gender distribution, and duration of diabetes when comparing the group of patients with diabetes who were treated with incretin-based therapies versus the patients with diabetes in the control group. These differences may affect the results.”
She adds the findings differ from results of randomized clinical trials involving more than 33,000 patients and notes the FDA has not yet reached any new conclusions about safety risks. But Public Citizen is not waiting for an agency announcement.
“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," says in its statement.