By Dr. Mercola | 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.
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 Januvia11and 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
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: