Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors. Alexandra E Butler et al. Published online before print March 22, 2013, doi: 10.2337/db12-1686. Diabetes March 22, 2013
You can read another discussion of what this study found HERE.
As soon as Dr. Butler's study came out, there was a rush to publish studies that supposedly refute it, funded, not so surprisingly by the companies who are earning billions of dollars from these highly profitable drugs.
The first such study was this one:
UPDATE 2-Doctors get good and bad safety news on diabetes drugs
This study claimed to find no sign of pancreatic disease with Onglyza.
This week, a larger, much more high profile study of Januvia was published in the New England Journal of Medicine in June of 2015. It was presented at the 2015 ADA conference which took place this past weekend and is being treated as if it removes all barriers to prescribing Januvia as it has supposedly dismissed all safety concerns about the drug.
This latest study is: Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. Jennifer B. Green, et al. NEJM, June 8, 2015DOI: 10.1056/NEJMoa1501352
Though the focus of the study was on cardiovascular outcomes, it was also reported as stating that there was no sign of more pancreatitis or pancreatic cancer in the group that took Januvia. This, apparently, is being interpreted as proving that these drugs do not cause these two conditions.
But the flaw in the reasoning used here is simple: Short term studies can't discover potentially fatal cancers that take a decade or more to be Detectable.
The first study only lasted 2 years, which is far too short a time for the changes in pancreatic architecture discovered by Dr. Butler to result in overt pancreatitis. The study just published in the New England Journal of Medicine study only lasted three years. But it would be quite possible to draw the same conclusion about the safety of smoking cigarettes if you limited your study to a three year period.
The reason it is so hard to detect early cancers of the pancreas--or the damaging structural changes that lead to pancreatitis is that there is no way to study the cells of a living pancreas without destroying it. That is why Dr. Butler was forced to study the pancreases of people who have died of head injuries.
Any study that assures you that these drugs are not damaging the pancreas which does not examine pancreatic tissue is not conclusive. Given how cancers progress, it will take 10 years or more for the pancreatic tumors these drugs are capable of growing to cause the epidemic of pancreatic cancer deaths that I fear is coming. By the time the deaths appear, it will be too late to do anything.
Until someone shows you 10 years worth of data that show no significant increase in cases of either pancreatitis or pancreatic cancer in people taking any incretin drug, be very skeptical of studies claiming they are safe.