The researchers wanted to see if, in fact, as claimed, the incretin drugs--the drugs that raise the concentration of GLP-1 or mimic GLP-1--cause an increase in the beta cell mass. These drugs have been promoted with the promise that they do, that they regenerate the pancreas. This is one major reason doctors prescribe them even when they appear to have no significant impact on their patients' blood sugars.
What the researchers found when they conducted rigorous studies of these pancreases found should make anyone taking any drug that increases the effect of GLP-1 completely rethink their drug strategy.
The study is 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
These Drugs Appear to Grow Lots More Beta Cells and Alpha Cells, But they Are Abnormal
What they found is this: These drugs do indeed appear to grow huge numbers of new beta cells and alpha cells in these people's pancreases. People with diabetes taking the incretin drugs had more than three times as much beta cell mass and alpha cell mass as people with diabetes not taking incretin drugs.
Unfortunately, the study also found that these cells were not growing in their normal patterns. They were found in "eccentrically shaped islets" and "in association with duct structures."
These abnormal beta and alpha cells were only found in the people who had been taking incretin drugs for a year or more, not in people with diabetes. Moreover, the researchers comment that the structures found in association with the pancreatic ducts were of the kind that are found in people with pancreatitis.
Even worse, the researchers found "glucagon expressing microadenomas" in three cases. An adenoma is a benign tumor made of glandular tissue which has the capacity of turning malignant. None were found in the people with diabetes who were not taking incretin drugs.
A glucagon-expressing neuroendocrine tumor was also found in one of the patients taking Januvia.
The researchers point out that,
Moreover, since the standard of care of a pancreatic neuroendocrine tumor, because of the risk of conversion to malignancy, even if benign, is surgical resection [i.e. removal], patients exposed to incretin therapy would seem to be at increased risk of requiring pancreatic surgery.Pancreatic surgery, even if it doesn't require the removal of your pancreas is very likely to damage it to the point where you become fully dependent on insulin. And that's the good outcome. The bad outcome is that they don't get all of the tumor, which converts to malignancy and you die of pancreatic cancer.
More importantly, the chances of doctors even noticing that one of these drugs is growing a tumore on your pancreas is nil--until it has grown to where it blocks ducts and causes extreme pain. The people autopsied in this study died of other causes unrelated to their diabetes or the health of their pancreases. The tumors they were carrying were unknown to their doctors.
The researchers that the causative factor here appears to be is the action of high levels of GLP-1 since both families of drugs caused the abnormal cell growth. Because of that, the same problems are almost certainly being caused by the newer incretin drugs, Onglyza, Victoza, Trajenta and any other DDP-4 inhibitor or GLP-1 mimic.
Since there were already troubling signs of pancreatitis and other kinds of adenomas associated with some of these newer incretin drugs while they were still in the testing phase, while it took many years for the possible association with pancreatitis to emerge with Byetta, these new drugs may be even more dangerous than Januvia and Byetta.
Talk to Your Doctor and Show Him or Her the Link to this Article Immediately
Tell them to hunt up the full text version. (I have read it.) It is compelling reading and should make any doctor not on the payroll of a drug company seriously reconsider prescribing any of these drugs.
That said, I fully expect to see this result spun by the drug companies, because the study also found that these drugs increased beta cell mass, something the drug companies have been hoping would turn out to be true.
But as these researchers point out, these new beta cells appear to be immature beta cells that are not functional. Some are expressing both insulin and glucagon, a characteristic of fetal human cells but not those of adults. And as they note, too. These people were all diabetic when they died, though they had 3 times as much beta cell mass as a normal person. Obviously, these beta cells were not the kind we want to fill our pancreases with.
And of course, the cost of this increase in beta cell mass was to fill the pancreas with invasive structures made up of a kind of fetal beta cell that isn't usually found in adults. Cells that are clumping together into glandular tissues aaround the pancreatic ducts in ways that aren't normal and, long term, may be far from benign.
Since there is no way to monitor what is going on in your pancreas without opening you up and taking a slice or two, the cost of any beta cell mass growth is obviously much too high.