May 4, 2009

New Study Links Januvia to Pancreatitis and Pancreatic Cancer

NOTE (April 2, 2013): Before you take Onglyza or Januvia please read about the new research that shows that they, and probably all incretin drugs, cause severely abnormal cell growth in the pancreas and precancerous tumors. You'll find that information HERE.

Original post:

It's a rat study but the rats are "Human transgenic rats" which might mean that the study is more applicable to humans than you'd think at first glance.

But the reason this new study is so important is that it is the FIRST study I have seen published that even looks at the question of whether Januvia might be promoting cancer. Since the study was funded by the maker of Januvia, Merck, it was spun in a way to make it sound like a solution has been found but close reading makes me question that this is true.

Given all the other forms of cancer that have been linked to the presence of DPP-4 inhibition--ovarian, lung, melanoma, and prostate, my guess is this study is only the beginning of the bad news we will be seeing about Januvia--unless the company is able to shut down such research with threats of lawsuits like those that were used to keep researchers from publishing data linking Avandia to heart attacks.

Here's the study:

Beneficial Endocrine but adverse Exocrine effects of Sitagliptin in the HIP rat model of Type 2 Diabetes, interactions with Metformin. Aleksey V. Matveyenko, , Sarah Dry, Heather I. Cox, Artemis Moshtaghian, Tatyana Gurlo1, Ryan Galasso, Alexandra E Butler and Peter C. Butler Diabetes DOI: 10.2337/db09-0058.

Note that the authors of this study include the Butlers, whose Mayo pancreas autopsy study I have discussed on my web pages. They are scientists who really know something about the pancreas.

You can read a more complete discussion of what this Januvia study found in Science News:

Popular Diabetes Treatment Could Trigger Pancreatitis, Pancreatic Cancer, Study Suggests

The rats used in this study are described thusly:
IP rats approximate both the islets and metabolism of people with Type 2 diabetes. The drugs were tested in 40 rats for 12 weeks.
Note also that the study lasted only 3 months.

What it found was that after exposing the human pancreas islets grown in these transgenic rats for only 3 months:
With the sitagliptin alone, however, the rats had abnormally high rates of cell production in their pancreatic ducts; a few developed an abnormality known as ductal metaplasia, and one developed pancreatitis.
When Januvia was combined with Metformin, the researchers did not see this effect. They speculate:
... metformin, trade name Glucophage, seems to counteract sitagliptin's adverse effect.

"The apparent protection against the unwanted actions of sitagliptin in the exocrine pancreas are intriguing and may offer a potential way of using the GLP-1 class of drugs safely," Butler said. "The protective effect may have been either by the actions of metformin to decrease blood glucose values or its recently appreciated properties as a tumor suppressive agent."
Left undiscussed are some major questions.

1. What happens when those pancreatic cells are exposed to Januvia for three years, rather than three months?

2. What happens to all the other cells in the body that also start overgrowing when DPP-4, a tumor suppressing gene, is turned off round the clock?

3. Why is this overgrowth only attributed to the impact of GLP-1 when researchers have linked DPP-4 inhibition to the spread of cancers in numerous published studies?

There's some very important information included in the abstract of this study that did not get discussed in the Science News report:

SIT+MET had synergistic effects to preserve beta cell mass in HIP rats. MET more than SIT inhibited beta cell apoptosis. MET enhanced hepatic insulin sensitivity, SIT enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. Beta cell function was partially preserved by SIT + MET.
What this is saying is basically Metformin alone had the same healthful effects as Januvia. Metformin inhibited beta cell death MORE than Januvia alone. Metformin alone lowered Liver insulin sensitivity--which will lower post-meal blood sugars dramatically in insulin resistant type 2s. Finally, though Januvia increased insulin sensitivity outside of the liver, it did so mostly in the presence of Metformin. Which also lowers insulin resistance outside of the liver on its own.

So the question you have to ask yourself if this: do you want to pay $185 a month to take Janumet, a drug whose efficacy mostly comes from Metformin--and risk cancerous changes in your pancreas cells (metaplasia) or pancreatitis? Or will you stick to the $4 generic Metformin which does pretty much the same thing without the cancer risk.


Scott S said...

This particular drug is so incredibly expensive that we all have a vested interest in understanding the possible issues that may be out there, as we all pay for it, especially with the Medicare drug benefit. The fact that older Americans consume these (and all) drugs at a disproportionately high level than other segments of the population, we should be looking at the data (ALL the data) very closely before opening our national wallet. The days of corporate subsidies seem to be, appropriately enough, under more scrutiny, so calling attention to these issues has become more important!

Anonymous said...

Well this all freaks me out. I am a stage 1 Pancreatic cancer patient( tumor removed) and have been on Januvia for two and half months. I have been experiencing stomach discomfort for a few weeks and has been getting worse. I will not be taking Januvia any longer!!!

Anonymous said...

Ultimately the patient should be the one who is most responsible in their health and care. To that point I applaud those individuals for looking closely at the data. I would point to all of the other oral antihyperglycemic medication's warnings, precautions, adverse reactions, drug interactions, and indications as well as Patient Counseling Information. If you notice Metformin, a generic medication and quite good I might add, has a black box warning for lactic acidosis. This potentially life threatening problem can occur in people taking Metformin although it is quite rare. Liver function tests should be run before taking Metformin and there are GI side effects that can be associated with taking Metformin. All medicines have some sort of issue with them as many are probably aware of. Many patients respond uniquely to different medicines. Pancreatitis in diabetic patients becomes a chicken or egg phenomenon. Which came first for the patient with type 2 diabetes? A diabetic has a compromised pancreas and in some cases develop pancreatitis. A patient with type 2 diabetes has defects in the islet cells in the pancreas and in many cases years prior to diagnosis. Clinical research hasn't answered the questions is a patient developing a compromised kidney because of type 2 diabetes or the other way around? I also agree with the posts, government subsidies must stop to corporations. But don't get caught up that all medications are dangerous if they are name branded and expensive. That's a different debate. Inform yourselves and talk with your healthcare provider.

Jenny said...


If you had read the page about metformin on my main web site, you would find that the fears about metformin causing lactic acidosis have been set to rest by research that shows that in huge populations lactic acidosis is no more common in people who take metformin than people who don't.

I present the research pro and con about every single diabetes drug currently prescribed on the main site. They are kept updated as new research comes in.

The sad thing is that doctors are not aware of even the most serious side effects and even more disturbing, research has found that they do not recognize these serious side effects when patients show up in their offices with their symptoms.

Patients are paying their doctors under the illusion that the doctors are better informed about their condition. In the case of diabetes many of us have found this to be an illusion.