View Full Version : The Science You Don't Hear About — DPP-4 Inhibitors Repeatedly Linked to Cancer...

20th December 2012, 12:05 PM
Another potential side effect of this class of drugs that you won't see in any drug advert or hear from your doctor is its potential link to cancer... Upon review of the medical literature, a number of studies have already indicated a connection of pancreatic, thyroid, colon, melanoma, and prostate cancer with DPP-4 inhibitors. Such studies include:

A 2006 study13 found that "the use of DPPIV inhibitors together with GLP-2 led to increased proliferation as well as elevated migratory activity. Therefore, the use of DPPIV inhibitors could increase the risk of promoting an already existing intestinal tumor and may support the potential of colon cancer cells to metastasize"
One 2008 study14 found that DPP-4 inhibitors may proteolytically inactivate local mediators involved in gliomagenesis (the formation and development of brain tumors). Another study published that same year15 linked the drug to prostate cancer
In 201016, researchers concluded that "although the data on the effects of DPP-IV inhibitors in humans are scarce, the increased risk of infections and the tendency towards a higher incidence of some tumors fall in line with experimental evidence suggesting the possibility of their adverse immunological and oncological effects"
According to a 2011 study in the journal Gastroentorology17,18: "data are consistent with case reports and animal studies indicating an increased risk for pancreatitis with glucagon-like peptide-1 based therapy. The findings also raise caution about the potential long-term actions of these drugs to promote pancreatic cancer, and DPP-4 inhibition to increase risk for all cancers"
Earlier this year, researchers warned19 DPP-4 "is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities.
This study indicates the need for exploring the cause and the importance of the disturbances in the serum DPP-4 activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanoma. Significant decline in serum DPP-4 activity found in melanoma patients compared to healthy controls might indicate its possible role in development and progression of melanoma, but further research needs to be done in order to fully elucidate the cause and the importance of observed changes in DPP-4 activity"

Logic Quiz: DPP-4 is a Tumor Suppressor, So What Happens When You Continuously Inhibit DPP-4?

A 2008 blog post on DiabetesUpdate20 spells out the concerns I have about this class of diabetes drugs:

"Two new studies grabbed my attention and should be of great interest to anyone taking Januvia. These studies looked at the impact of inhibiting DPP-4 on the growth of two different kinds of cancers. This is important because the way Januvia lowers blood sugar is by inhibiting DPP-4. It does this because DPP-4 is a protease (an enzyme that chops up protein chains) that, among other things, destroys a hormone, GLP-1, that helps control blood sugar levels. When you inhibit DPP-4, GLP-1 levels to rise and blood sugars drop.

But none of the drug industry-sponsored testing for the safety of Januvia looked at the other things that DPP-4 does. Fortunately, some academic researchers not-funded by drug makers are doing this and what they are finding should make any sane person stop taking Januvia. Because it turns out that DPP-4 is also a tumor suppressor. And when you inhibit it, cells that have become cancerous get a 'get out of jail free' card."

Just think about the logic (or rather, the lack thereof) of taking a drug that continuously inhibits one of your body's natural cancer suppressing mechanisms! According to Januvia's drug information, the drug inhibits the DPP-4 enzyme for 24 hours, and you take it daily, effectively permanently blocking the activity of a tumor suppressor gene. Yet none of the safety studies on Januvia addressed its impact on tumor growth!

Is this wise? I don't see how it can be — especially for a disease that doesn't require drug treatment to be resolved. The blogger received the following emailed note21 from a researcher who worked on one of the studies listed above (the author and study in question was not identified, and probably for good reason):

"... Inhibiting DPPIV function in general (according to ours and others research) may not be a great idea. I believe that decrease or loss of DPPIV may be associated with cancer initiation or progression. We have shown that loss of DPPIV is indeed associated with melanoma, prostate and lung cancers. Importantly our work has shown that restoring DPPIV can suppress the tumor growth..."

In a 2010 article in the journal Diabetes Care22 entitled "GLP-1–Based Therapy for Diabetes: What You Do Not Know Can Hurt You," the authors state:

"In conclusion, we believe it is premature to conclude that the GLP-1 class of drugs has been established as having a good safety profile and is appropriate for a relatively early choice of therapy for type 2 diabetes.

There are grounds for concern that the GLP-1 class of drugs [which includes DPP-4 inhibitors] may induce asymptomatic pancreatitis and, over time in some individuals, induce pancreatic cancer... [T]he implications of the data are sufficiently serious that continuing to promote this class of drugs without establishing clear experimental evidence to permit the concern to be rejected is irresponsible. Moreover, arguably patients prescribed these drugs should be made aware of the potential risks of pancreatic cancer."

"Researchers" Who Debunk Cancer Link are Paid Spokespersons for Big Pharma

Not surprisingly, some researchers have spoken out against studies linking DPP-4 inhibitors and GLP-1 agonists (such as Byetta, which was approved in 2009) with various cancers, calling such findings "flawed." Alas, it may be wise to look at who these people are, and who pays them. In an IBJ.com article published last year23, Dr. Michael Nauck, head of the Diabeteszentrum Bad Lauterberg in Harz, Germany said, with regards to studies linking GLP-1 agonist drugs Byetta and Victoza with increased risk of cancer:

"The bulk of findings tends to speak against such an association... There is no general agreement."

According to the article:

"Nauck debated Peter Butler of the University of California at Los Angeles at the European Association for the Study of Diabetes meeting Friday on whether so-called GLP-1 therapies increase cancer risk. Sales of the drugs may be hurt should Butler's view prevail that there are signs of increased cancer from the drugs. He and other UCLA researchers said in a study this year that a review of a database of side effects showed patients taking Byetta and a Merck & Co. drug [Januvia] had a higher chance of developing pancreatic or thyroid tumors. The treatments are safe and there's no evidence of a higher cancer risk, according to the manufacturers of the drugs."

Who is Michael Nauck 24? While his biography may not spell it out, Professor Nauck has been a speaker and consultant25 for a long list of pharmaceutical companies, including Amylin Pharmaceuticals (the maker of Byetta), Novo Nordisk (maker of Victoza), Merck, AstraZeneca, Bristol Myers Squibb, Eli Lilly & Co, and GlaxoSmithKline, just to rattle off a few. Note the first two I listed are the very makers of the very drugs he's arguing the safety of. So much for an independent opinion. He's also received grants and financial research support from a number of drug companies.

According to Peter Butler26, co-author of the Gastroenterology study listed earlier, the GLP-1 drug class "could have serious unintended and unpredicted side effects." His research discovered that patients taking Byetta and Januvia had a:

Six-fold increased chance of pancreatitis, and
Nearly three times greater rate of pancreatic cancer
In a September 2011 article in Bloomberg27, Matteo Monami, a physician at the University of Florence and Carreggi Teaching Hospital in Italy called Butler's study "an erroneous analysis," stating that its results "are really not reliable at all." Monami countered Butler's findings with a meta-analysis28 of his own, which not only found no increase in cancer or pancreatitis for DPP-4 inhibitors like Januvia, but also "possible protection from cardiovascular events."

What the media failed to report was that Monami is a paid spokesperson for Merck (the maker of Januvia — the drug at the center of the controversy), Astra Zeneca, Bristol Myers Squibb, Eli. Lilly, Novo Nordisk, and Takeda. Knowing he's a paid Big Pharma spokesperson, surely no one can be surprised that Monami's analysis and "professional opinion" clears his employers' drugs of any potential cancer links...

Billions of Dollars at Stake...

When Merck and the FDA finally agree that DPP-4 inhibitors are linked to cancer, it will kill several of the most recent drug developments for diabetes. Untold hundreds of millions, if not billions of dollars have already been invested in getting these new drugs to market. And the profits from these drugs are expected to be in the tens of billions at minimum..

According to Merck, Januvia is now the number one best-selling drug in the oral diabetes market. Should such a blockbuster drug be proven to be connected to cancer, it would be a HUGE loss not only to Merck, but several other major pharmaceutical companies that have developed similar drugs.

One of the most horrific parts of this is the fact that cancer can take decades to form — unless the drug dramatically speeds up the process by inhibiting your body's ability to suppress tumor growth. Merck's lethal drug Vioxx was only withdrawn from the market after its lethality became too obvious to ignore. Ditto for the dangerous diabetes drug Avandia. Those drugs caused heart attacks and stroke. Cancer, on the other hand is not something that will tend to make people keel over after a relatively short period of time.

They could make MASSIVE amounts of money from these clearly dangerous drugs while cancer slowly and quietly grows in patients taking them, while biased shills maintain that the science is still "unclear." I for one would urge you to reconsider taking any kind of DPP-4 inhibitor. Why risk cancer for an ailment you can effectively address without ANY drug at all?

Source - Dr Mercola