The study, which examined insurance records for more than 2,500 diabetics between February 2005 and December 2008, found that patients hospitalized with pancreatitis were twice as likely to be taking one of these drugs, as opposed to a control group of Type 2 diabetics who did not have pancreatitis. The study did not examine other meds that were not yet available at that time (here is the abstract).
The issue immediately raised was whether these results might alter treatment practice by physicians. Not surprisingly, the drugmakers issued statements standing by the safety of their medicines, while acknowledging the risks have been detected in the past. ”The study is another data point in the larger body of research to date,” argued Bristol-Myers, which also sells Bydureon, the Byetta follow-up.
The American Association of Endocrinologists and the American Diabetes Association issued a joint statement to dispel concerns (here it is). The groups noted the analysis is a retrospective study, not a prospective, randomized controlled clinical trial, which many regard as a gold standard for ferreting out safety concerns
And some Wall Street analysts scoffed, citing limits on the study design and methodology, such as statistically significant and meaningful imbalances favoring the patients in the control group in several characteristics that are known to be important risk factors for acute pancreatitis. And some also noted the lead author has a controversial track record of publishing studies that highlight safety concerns with various drugs (back story).
Now, though, the FDA has weighed in. Yesterday, the agency disclosed it is "evaluating unpublished new findings by a group of academic researchers that suggest an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients with type 2 diabetes treated with a class of drugs called incretin mimetics," according to its statement.
Why? Patient deaths. "The findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes," the FDA says, adding that its requested the researchers provide the methodology used to collect and study these specimens and to provide the tissue samples so the agency can further investigate potential pancreatic toxicity associated with the incretin mimetics."
Which drugs are in question? Besides Januvia and Byetta, there is also Bydureon; Merck's (MRK) Janumet; 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. The drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal.
The FDA noted that the labeling for the drugs already include warnings about the risk of acute pancreatitis over the past few years (see this and this), but the agency has not previously communicated about the potential risk of pre-cancerous findings linked to the incretin mimetics.
Of course, this sort of warning gets disseminated very quickly and one side effect was a hit on the stock prices of some of the drugmakers. However, another point worth noting was the negative reaction to the recent study. Granted, pancreatitis is not a new problem and there may well be issues with the recent study, which was published in JAMA Internal Medicine.
"We are skeptical that this study will have any meaningful impact on use of these therapies JAMA Internal Medicine is not widely read or high impact among physicians, the evaluation is a post hoc association analysis fraught with error and the authors are from the School of Public Health at Johns Hopkins, so the likelihood that this will be viewed as anything more than informational is unlikely," one analyst wrote in a research note.
Just the same, the FDA cited the study in its statement, suggesting the agency had reason to take the conclusion seriously. Of course, the FDA is not always correct, either, and agency officials have spent the last few years attempting to seriously emphasize safety concerns in the wake of various scandals over the past decade, notably, the Vioxx painkiller and the Avandia diabetes pill.
Now, though, the resarchers may eventually be able to tell the naysayers 'I told you so.' Not that anyone wants to see a serious safety concern with an otherwise useful medicine. And the FDA review is nowhere near complete. But the latest development suggests that assessing studies that do raise such issues may well merit consideration and the rush to criticize these sorts of findings may deserve an equal amount of rumination.
question mark pic thx to purpleslog on flickr