New Diabetes Drug Can Increase Cancer Risk

December 20, 2012 |173,205views|

Story at-a-glance

• Several studies of the newest blockbuster drug for diabetes, Januvia, have implicated these very common drugs to cause a number of different cancers. They will likely be removed from the market but perhaps not until they’ve killed many
• There simply is no reason these dangerous drugs should ever be used as they fail to treat the cause of the disease. Anyone on them now ideally should stop taking them and follow a healthy eating plan, which will radically improve, if not completely resolve, their diabetes
• Acknowledged side effects of Januvia and Janumet, include anaphylaxis and acute pancreatitis—both of which can be lethal. Anaphylaxis is in fact such a grave hazard with this drug that it actually carries a black box warning for lactic acidosis: “If acidosis is suspected, discontinue Janumet and hospitalize the patient immediately.”
• This new class of drugs inhibit the enzyme DPP-4 which also happens to be a tumor suppressor. Studies have shown that when you suppress DPP-4 (which is precisely what these drugs do), cancer cells are allowed to proliferate. 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
• None of the safety studies on Januvia addressed its impact on tumor growth prior to approval
• 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’s a HUGE loss not only to Merck, but several other major pharmaceutical companies that have developed similar drugs. Drug companies like Merck could make MASSIVE amounts of money from these clearly dangerous drugs while cancer slowly and quietly grows in patients taking them

 

 

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By Dr. Mercola

Diabetes has increased more than 700 percent in the last 50 years. Today, more than one in four Americans are either pre-diabetic or have full-blown diabetes.

The conventional treatment route includes a variety of diabetes drugs, some of which have been found to do far more harm than good. Rosiglitazone, sold under the names of Avandia, Avandamet and Avaglim, is perhaps the most well-known in this category of unmitigated disasters.

 

Avandia Part of Worst Drug Fraud in History

 

This past summer, drugmaker GlaxoSmithKline agreed to a record-breaking $3 billion settlement over the sales and marketing practices of several of its drugs, including the dangerous diabetes drug Avandia. The payment is the largest fraud settlement in U.S. history, and the largest fine ever paid by a drug company.

Avandia was found to be profoundly dangerous — a fact hidden by GSK for over 10 years, as they knew it would adversely affect sales¹.

This was revealed in a Senate Finance Committee report, released by Max Baucus and Charles E. Grassley in February 2010. The report also asked why the FDA allowed a clinical trial of Avandia to continue even after the agency estimated the drug had caused an estimated 83,000 heart attacks between 1999 and 2007².

Avandia hit the market in 1999 and quickly became a blockbuster drug. By 2006 its annual revenue was $3.2 billion. A year later, a damning study published in the New England Journal of Medicine (NEJM) linked it to a 43 percent increased risk of heart attack and a 64 percent higher risk of cardiovascular death than patients treated with other methods³.
This is a steep price, to say the least, for a disease that does not require drugs to begin with.

There were many articles and reviews published about Avandia following the New England Journal of Medicine study, but research from the Mayo Clinic revealed that 90 percent of scientists who wrote favorable articles about the drug had financial ties to GlaxoSmithKline⁴. Unfortunately, a committee of independent experts still recommended that Avandia remain on the market, despite its many risks, and a U.S. Food and Drug Administration (FDA) oversight board voted 8 to 7 to accept the advice.

On September 23, 2010, the FDA restricted access to Avandia⁵, but it didn't take it off the market. Under the ruling, the drug is still available to patients not already taking it, but only if they are unable to achieve glycemic control using other medications and, in consultation with their health care professional, decide not to take a different drug for medical reasons.

Shockingly, current users of Avandia were told to continue using the medication if they appeared to be benefiting from it and they acknowledged that they understood the risks. Doctors had to attest to and document their patients' eligibility and patients had to review statements describing the cardiovascular safety concerns.

Unlike the US FDA, British regulators ruled that the benefits of Avandia no longer outweighed the risks, and so, in late September 2010, they told 90,000 British diabetes patients to stop taking it.

 

DPP-4 Inhibitors — Another Disastrous Diabetes Drug

 

Dr. Ron Rosedale, one of my mentors on the importance of insulin first alerted me to this issue in our recent interviews we had but are not yet published. This is another potential disaster-in-the-making, namely that of Dipeptidyl peptidase-4 inhibitors⁶ (DPP-4 inhibitors), also known as gliptins (specifically, gliptins decrease the breakdown of glucagon-like peptide-1, or GLP-1). These belong to a class of hypoglycemic drugs used to treat type 2 diabetes. DPP-4 inhibitors work by reducing glucagon and blood glucose levels⁷ (inhibiting glucagon release results in increased insulin secretion and decreased blood glucose).

The first drug in this class — Sitagliptin, manufactured by Merck and sold under the name Januvia⁸,⁹ — received FDA approval in 2006¹⁰. Saxagliptin (Onglyza), another DPP-4 inhibitor, was approved in July 2009, followed by Linagliptin (Trajenta) in 2011. A number of additional DPP-4 inhibitors are currently under development.

I was among the first to publicly warn that another of Merck's drugs, Vioxx, would kill thousands from heart disease. The drug indeed wound up killing over 60,000 people before Merck removed it from the market in 2004.
To compound this problem even further, Merck has announced that it has successfully completed a Phase II trial of a once-a-week version of a DPP-4 inhibitor. In pharma announcements and in its own company literature, Merck indicates that the once-a-week version is also being tested in combination with certain statin drugs, such as Lipitor and Simvastatin. The reasoning for these drug combinations is that diabetics fall under the guidelines of being statin candidates because they have a higher cardiovascular risk, but 40 percent of diabetics don't take them.

The idea is to create a combination drug containing both a DPP-4 inhibitor and a statin. So one drug will radically increase your risk of cancer, and the other increase your risk of heart failure. These are virtually guaranteed side effects from these drugs when taken individually, but what has not even been studied is the synergistic toxicity of taking these dangerous drugs together.

So far, Merck has discussed the alleged efficacy of their once-a-week DPP-4 inhibitor. However, clinicaltrials.gov indicates that the SAFETY trial isn't until Phase III, which is just now beginning. Still, with or without company-performed (read biased) safety trials, there's plenty of reason to suspect these drugs can, and probably will, spell severe trouble for diabetics who take them. For example, Sitagliptin, sold under the names Januvia¹¹ and Janumet, has a number of admitted side effects, including:

• Low blood sugar
• Allergic reactions and anaphylaxis (rash, hives, swelling of face, lips, tongue and/or throat)
• Acute pancreatitis
• Death

Anaphylaxis is in fact such a grave hazard with this drug that it actually carries a black box warning for lactic acidosis: "If acidosis is suspected, discontinue Janumet and hospitalize the patient immediately" According to diatetesselfmanagement.com¹²:

"... DPP-4 was discovered through its association with the immune system, and some researchers thought that inhibiting it might impair the immune system. So far, data from clinical studies have not demonstrated a serious immunosuppresive effect. They do indicate, though, that sitagliptin increases the risk of upper respiratory infections and nasopharyngitis (inflammation of the nose and pharynx), found in 6.3% and 5.2% of study subjects, respectively, who took sitagliptin versus 3.3% and 3.4% for placebo.

The most worrying side effects are those reported since the drug came onto the market.

These reactions seem to be allergic in nature and include anaphylaxis, a bodywide reaction that results in low blood pressure, and angioedema, a swelling of the tongue, face, and throat. Both of these may be life-threatening. The reactions have occurred anytime from immediately after taking the first dose until three months after starting the drug. There have also been reports of skin reactions, including a very severe type of drug reaction called Stevens–Johnson syndrome. Other diabetes drugs are not typically associated with Stevens–Johnson syndrome."

 

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

 

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?

 

Type 2 Diabetes is Nearly 100 Percent Preventable... and Reversible Without Drugs

 

There is simply no doubt in my mind that these drugs will be removed from the market, but not after many years, potentially decades, and likely after they have killed tens of thousands of people. But you don't have to needlessly suffer and wait till they are formally removed. You can stop taking them now. Reversing type 2 diabetes is one of the simplest and most straight-forward treatments in all of medicine.

It's important to understand that many of the conventional recommendations for treating diabetes are not only flawed but dead wrong, and I discussed the reasons why in this previous article. To reverse the disease, you need to recover your body's insulin and leptin sensitivities – the ones that are so badly upset by eating a poor diet. The ONLY way to accomplish this is through proper diet and exercise. There is NO drug that can correct leptin signaling and insulin resistance. 

It will be absolutely crucial to eliminate ALL sugars and virtually all grains from your diet. You want to strive for an ultra-low carbohydrate diet seeking to restrict your carbs to high fiber vegetables only. You can replace the missing carbs with high quality fats like coconut oil, which are rapidly broken down and consumed as fuel so you won't feel as tired or fatigued when you make the transition to fat burning mode. Using intermittent fasting and restricting all your calories to a 6-8-hour window will also radically help your ability to transition to fat burning mode and improve your insulin and leptin signaling.

Adhering to the following guidelines can help you do at least three things that are essential for successfully treating, and reversing, diabetes: recover your insulin/leptin sensitivity, help normalize your weight, and normalize your blood pressure:

• Severely limit or eliminate sugar and grains in your diet, especially fructose, which is far more detrimental than any other type of sugar. Following my Nutrition Plan will help you do this without too much fuss. Likely long before you work your way up to the Advanced Section, your type 2 diabetes will be under control without any drugs.
• Exercise regularly. Exercise is an absolutely essential factor, and without it, you're unlikely to get this devastating disease under control. It is one of the fastest and most powerful ways to lower your insulin and leptin resistance. I recommend reviewing my exercise program for tips and guidelines. It is also critical to work your way up to include some Peak Fitness exercises.
• Avoid trans fats.
• Get plenty of omega-3 fats from a high quality, animal-based source, such as krill oil.
• Optimize your vitamin D levels. Recent studies have revealed that getting enough vitamin D can have a powerful effect on normalizing your blood pressure.
• Optimize your gut flora. Your gut is a living ecosystem, full of both good bacteria and bad. Multiple studies have shown that obese people have different intestinal bacteria than lean people. The more good bacteria you have, the stronger your immune system will be and the better your body will function overall.
Fortunately, optimizing your gut flora is relatively easy. You can reseed your body with good bacteria by eating fermented foods (like natto, kefir, raw organic cheese, miso, and fermented vegetables) or by taking a high-quality probiotic supplement.

• Address any underlying emotional issues and/or stress. Non-invasive tools like the Emotional Freedom Technique (EFT) can be extremely helpful and effective.
• Get enough high-quality sleep every night.
• Monitor your fasting insulin level. This is every bit as important as your fasting blood sugar. You'll want your fasting insulin level to be between 2 and 4. The higher your level, the worse your insulin sensitivity is.

[+] Sources and References 1 Associated Press February 21, 2010 2 Searcy Denney Scarola Barnhart & Shipley Attorneys at Law 3 New England Journal of Medicine 2007 Jun 14;356(24):2457-71 4 Bloomberg March 18, 2010 5 FDA.gov Press release September 23, 2010 6 GlobalRPH.com, DPP-4 Inhibitors 7See ref 3 8 Januvia.com 9 Drugs.com Drug Approval History, Januvia 10 Diabetesselfmanagement.com, DPP-4 Inhibitors 11See ref 2 12See ref 3 13 Regulatory Peptides 2006 Dec 10;137(3):147-55 14 Physiol. Res. 57: 443-449, 2008 15 Clinical and Experimental Metastasis 2008;25(7):765-76 16 Diabetes Research and Clinical Practice May 2010; 88(2): 125-131 17 Gastroentorology July 2011;141(1):150-6 18 DocGuide.com, Gastroentorology July 2011 19 BMC Immunology 2012, 13:48 20 Diabetesupdate.blogspot.com December 2008 21See ref 14 22 Diabetes Care February 2010: 33(2); 453-455 23 IBJ.com September 16, 2011 24 Michael Nauck Biography (PDF) 25 Peerviewpress.com, Michael Nauck, MD 26 Bloomberg September 16, 2011 27See ref 20 28 Researchgate.net, Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials [+] Comments (175)

Source: Newest Blockbuster Diabetes Drug Can Increase Your Risk of Cancer