Scrambled Eggs

Scrambled Eggs

This week the diabetes world has gathered in Lisbon for the 47th annual EASD conference.  Along with the slew of study data released this week a hot topic at this year’s EASD is the debate over the safety of two relatively new and popular diabetes treatments, GLP-1 and DPP-4.  This week a panel will debate whether these two therapy options are linked with an increased cancer risk and pancreatitis. Although Amylin (NASDAQ:AMLN) and Merck (NYSE:MRK) are the most impacted by this debate, it’s fair to state that almost every company in the diabetes drug world will be impacted.

As Diabetic Investor has been reporting GLP-1 therapy is gaining momentum and Januvia from Merck, a DPP-4 has become a major blockbuster.  Novo Nordisk (NYSE:NVO) has Victoza another GLP-1, while Sanofi-Aventis (NYSE:SNY) released data on their GLP-1 Lyxumia® earlier this week; and let’s not forget about Lilly (NYSE:LLY) who besides being partnered with Amylin on Byetta and Bydureon (GLP-1’s) also has Tradjenta, a DPP-4, on the market.  Bristol Myers (NYSE:BMY) and AstraZeneca (NYSE:AZN) are partners with Onglyza another DPP-4. It’s also true that nearly every company in the diabetes drug world has some sort of GLP-1 in their pipeline.

The basis for this upcoming debate is a study published in Gastroenterology entitled Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-like Peptide-1–Based Therapies by Michael Elashoff; Aleksey V. Matveyenko; Belinda Gier; Robert Elashoff and Peter C. Butler. According to the study the authors “examined the US Food and Drug Administration’s database of reported adverse events for those associated with the dipeptidyl peptidase–4 inhibitor sitagliptin and the glucagon-like peptide-1 mimetic exenatide, from 2004–2009; data on adverse events associated with 4 other medications were compared as controls. The primary outcomes measures were rates of reported pancreatitis, pancreatic and thyroid cancer, and all cancers associated with sitagliptin or exenatide, compared with other therapies.”

Based on this examination the authors concluded; “These 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.” The authors also state; “For now this analysis of the FDA data base does not establish that pancreatitis, pancreatic and thyroid cancer are caused by GLP-1 based therapy. It simply raises the level of concern that they may be and that the appropriate prospective studies are required to rule them out.”

The authors also acknowledge the limitations of their data set stating; “Analysis of the FDA AERS database is not the ideal mechanism to compare adverse event rates between drugs. Limitations of the FDA AERS database, including incomplete data and reporting biases, are well-known.”

As if this debate isn’t enough of a problem another study published in the most recent issue of the Archives of Internal Medicine entitled “Communicating Uncertainties About Prescription Drugs to the Public” by Lisa M. Schwartz, MD, MS and Steven Woloshin, MD, MS concludes; “A substantial proportion of the public mistakenly believes that the FDA approves only extremely effective drugs and drugs lacking serious side effects.”

The authors went onto to state: “Despite uncertainties about benefits and harms, many new drugs are aggressively promoted to the US public in no uncertain terms. For example, direct-to consumer (DTC) advertising for Zetia and Vytorin (approved only on the basis of improving lipid profiles) reached $200 million (sales reached $1.8 billion) in 2007, the year before a randomized trial reported in the New England Journal of Medicine failed to detect any clinical benefit. Advertisements only included a statement acknowledging that the clinical benefit was unknown after publication of this trial. In 2000, a year after it was approved by the FDA, DTC advertising for Vioxx surpassed all other drugs, reaching $500 million (sales reached $2.4 billion) by 2003, the year before it was withdrawn from the market because it caused myocardial infarction and strokes. The FDA has never required advertisements to acknowledge uncertainties inherent in all new drugs.

While regulators and many clinicians understand these uncertainties, the public may not. Enthusiasm for Zetia and Vioxx (or Avandia, ProCrit, etc.) might have been dampened had consumers known to look for drugs approved based on patient outcomes or drugs with a longer safety record.”

The fact that this study was conducted and published shows just how out of touch some researchers have become with how things work in the real world. While this may come as a shock to these eggheads, most people don’t have advanced medical degrees nor do they have the time to read study data for the drugs their physicians are prescribing.

Based on the way studies are written Diabetic Investor doubts this would do any good even if they did. The conclusion of the GLP-1 study is a perfect example of this; “For now this analysis of the FDA data base does not establish that pancreatitis, pancreatic and thyroid cancer are caused by GLP-1 based therapy. It simply raises the level of concern that they may be and that the appropriate prospective studies are required to rule them out.”  A patient reading that statement still has no idea if the drug their tacking is safe or not. Nor can their physician give them a simple yes or no answer to the common question asked by almost every patient- Is this drug safe?

In the real world patients want simple answers to complex questions. In the real world patients, rightly or wrongly, believe that once the FDA approves a drug or device that it is safe to use. In the real world, patients rely on their physicians to know which drugs are safe. In the real world, even when an approved drug is found to have serious issues, this does not stop patients and their physicians from trying newly approved drugs that have limited track records. In the real world many patients believe if a drug is new it must be better than the “older” drugs on the market.  Again like it not, many people believe newer is better.

Diabetic Investor also believes it’s ludicrous to imply that just because drug companies aggressively promote their drugs that they somehow are aware that their particular drug has problem and that they are more concerned with profits rather than patient safety. Like Diabetic Investor these drug companies understand that there is no such thing as a completely safe drug and that adverse events are unfortunately are part of the business. Only these eggheads would believe that a company like GlaxoSmithKline (NYSE:GSK) wanted to have issues with Avandia or that Glaxo somehow knew in advance that Avandia would be linked with adverse cardiovascular events. As Diabetic Investor has stated consistently on this issue Glaxo may have made mistakes with Avandia however it is also there is an equal amount of issues with now famous meta-analysis that lead to Avandia’s demise.

Yet, newer drugs are not the only drugs coming under attack. Recent study has tried to link insulin usage to higher mortality rates. According to a just published that analyzed over 3,400 French adults over a period of 14 years found that those with Type 2 diabetes who received insulin treatment had a significantly increased risk of death.

According to Dr. Emilie Bérard, an epidemiology researcher at the University Hospital Center in Toulouse, France, patients with diabetes who were “treated with insulin at baseline were at increased risk of all-cause mortality.” Dr. Bérard spoke at the yearly meeting of the European Society of Cardiology, adding that the data “provides further information to the debate on the risks and benefits of increasing hypoglycemic treatments.”

While there are many flaws with this study, it’s just one more example of this foolish belief in the research community that there is such a thing as a completely safe drug. Diabetic Investor believes this growing preoccupation with adverse events is not just foolish but dangerous. While no one would argue that drugs should not be as safe as reasonably possible, the fact remains that there is no such thing as a completely safe drug and all drugs carry some degree of risk. Yes it would great if drug makers could eliminate every conceivable adverse event, this just isn’t possible and quite frankly it’s foolish to believe it can be done.

The danger here is that patients and physicians will stop using drugs, new and old. Someone should explain to these eggheads that diabetes is serious disease state and more, not less, drugs are needed. Are these eggheads not cognizant of the fact that diabetes is growing at epidemic rates and has become a worldwide healthcare and economic crisis? Are they not aware that nearly two-thirds of all patients are not properly controlling their diabetes and this fact leads to devastating and costly complications? Diabetic Investor wonders what these eggheads would tell a physician on how they should treat diabetes. The fact is although it would be nice if patients ate properly and exercised regularly, diet and exercise alone are not enough to control diabetes for the majority of patients and prescription medications are not just essential but lifesaving.

It’s equally true that the mere fact a patient has diabetes makes them more susceptible to certain adverse events, i.e. pancreatitis. A fact Diabetic Investor pointed out back when this issue first came to light. Yet, it didn’t seem to matter to these eggheads that even though patients using Byetta experienced a LOWER incidence rate of pancreatitis than diabetes patients in general they still felt it necessary to alarm the public, a trend that unfortunately that appears to be continuing with this latest batch of research.

Diabetic Investor does understand the need to be diligent with research and when conducted properly these findings can be useful. Patients and their physicians must be fully informed as to both the possible risks and potential rewards of the drugs used to treat diabetes. However, the alarmist nature of recent research has created the perception that an FDA approval is meaningless. That somehow drug companies know in advance that drug will develop issues years after it was approved. Keep in mind that it took over seven years to discover that patients using Avandia and Actos experienced a higher rate of bone fractures. An adverse event that did not appear while the drugs where undergoing their extensive clinical study.

Like so many aspects of our society today where extreme viewpoints garner the public’s attention, a balanced view is deemed unacceptable. The fact is the risk of adverse events cannot be eliminated, as noted earlier this is the nature of the beast. It is also true the risk of not approving or not using these drugs is equally dangerous.  Given the runaway epidemic of diabetes and its unacceptable consequences both from a healthcare and economic perspective, it’s critical to have a balanced approach. Yes patients and physicians should be fully informed of the real risks and rewards of the medications they use. Just as important they also need to understand the corresponding risks of uncontrolled diabetes.

While it may be impossible to develop a system that provides simple answers to complex questions, we should not forget about the simplest principal of all – common sense.  This is a principal these eggheads ignore, as they seem to believe they know better than everyone else and that the patient and their physician lack the capacity to make informed decisions when presented with all relevant facts. In the real world the majority of patients understand that there is no such thing as a completely safe drug. They also understand that if they don’t control their diabetes they could experience serious complications. Or put another way, patients aren’t stupid and shouldn’t be treated as if they are.

To Diabetic Investor these eggheads lack the basic understanding of what it means to live in a free society. That individuals lack the capacity, when presented with all the facts, to make an informed decision.  Worse still is their ivory tower belief system and failure to grasp how things work in the real world.  These eggheads want to take away one of the fundamental principles on which this great nation was built upon – Freedom of Thought. As Bergen Evans noted; “Freedom of speech and freedom of action are meaningless without freedom to think.”