New Study Links Januvia to Pancreatitis and Pancreatic Cancer

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.