Endodoc

Just to keep you up on the latest news; there was a long article in the New York Times today written by Stephanie Saul and Gatrdiner Harris, entitled “Years Ago, Agency Was Warned of a Drug’s Risks,” (Section C, page 1). The gist of the article was that several years ago the FDA was warned by at least one physician, Dr. John Buse, that rosiglitazone (Avandia) might pose cardiovascular risks for patients with diabetes. Dr. Buse is soon to be the president of the American Diabetes Association. It is interesting that he has done studies for Eli Lilly on a competing drug, Actos. I like Dr. Buse but deep down might there be some bias or conflict of interest in his current criticisms? Maybe not?
Enter the cool-headed British

Most interesting to me was an editorial published yesterday on-line in the distinguished British medical journal, The Lancet. The editorial (I couldn’t find out who wrote the piece), which appeared in my e-mail today courtesy of the Lawson Wilkins Pediatric Endocrine Society, summarized the Avandia “press” over the past 2 days. The author, like me, was surprised at the incredible uproar over the Nissen paper in the New England Journal of Medicine (see my last entry for the details) and the FDA warnings.
The Lancet editorial pleaded for calm and reason; there were already considerable data showing increased cardiovascular risks for patients with type 2 diabetes who took Avandia. The author suggested we might wait until more data are available from large prospective studies that might allow us to sort things out better (just to remind you, the paper by Nissen and colleagues was a meta-analysis of ALREADY PUBLISHED data. Oh, what are the British to think of us?

What does the Avandia story tell us?

Clearly, the way we in American medicine and our patients get information about drugs and other therapies that are commonly used needs rethinking. The Avandia “the sky is falling” story should be embarrassing to us all. Pharmaceutical companies, physicians, the medical journals, and the FDA need to do a much better job in sorting out the risks and benefits of this or that therapy; every treatment, drug or otherwise, has a risk/benefit ratio- sometimes the risks are unknown, but it’s worth knowing that.

I believe most physicians who prescribe this or that drug are very shaky regarding the risk side of things; if physicians do not know the risks of the drugs they prescribe, patients will not get the chance to “weigh in” on whether the recommended therapies are right for them. All physicians, including yours truly, are guilty of not always sharing enough information with patients about a recommended therapy, even if we do know the risks involved. I wonder how many physicians who have prescribed Avandia were even aware of the data suggesting increased risks of heart disease? Don’t get me wrong, even if a drug or other therapeutic approach has risks, it may be well worth the risk for the potential benefits, and that may be the case with Avandia. Who knows?

I have been nothing short of astonished about the hype over the New England Journal of Medicine (NEJM) article published yesterday (actually published on-line prior to it’s scheduled hard-copy release on June 14) on the possible dangers of a widely-used drug for people with type 2 diabetes. In summary, the article, written by Stephen Nissen and colleagues at the Cleveland Clinic, reviewed 44 previously published reports on the use of Avandia and concluded there was a 43% increased risk (relative risk 1.4) of heart attack in people taking the drug compared to those taking placebo or a different diabetes drug. Thus, here we have a meta-analysis- a study that combines the results of actual clinical studies and analyses the data as if they came from a single large study. This is a well-established statistical tool but one with many pitfalls.

How this all unfolded

First, those of us who subscribe to the NEJM, received an e-mail on May 21 with the article. Apparently, the press release was not to take place until after the stock market closed on the 21st. But, earlier in the day of May 21, the report was released by several news services and chaos ensued. The maker of the drug, GlaxoSmithKline had a 7% drop in their stock by the close of the market on the 21st. They, of course, issued a statement defending the drug’s safety. The FDA issued an “alert,” warning patients taking the drug to check with their doctors.

There is more!

In an article today in the New York Times, the interesting course of events and the economic impact of the NEJM report are detailed nicely. The article, written by Stephanie Saul made the front page of the business section and was entitled “Heart Risk Seen in Drug For Diabetes.” The new report summarized the NEJM report and the economics of diabetes drugs (big bucks). In addition, Ms. Saul tells us that as far back as last August, the FDA had data showing increased risk of heart disease in patients taking the drug.

Why so much excitment over this study?

I am amazed at the hype over this report and it does not say much good about the news media, the FDA, medical journals, and doctors. This morning, the news of the dangers of Avandia were everywhere- I just couldn’t hide from it: I even heard about it on CNN when I was waiting to pick up my car (a hybrid) which was getting an oil change.

This is not the way for important medical information to be disseminated. First, I would question how important the news is. Remember, all of the studies that the Nissen article had already been published and those of us “in the field” already knew there were concerns about the cardiocascular side effects of Avandia. The increased risks of heart failure with the drug and with other “glitazones” is well known already. Even worse, along with the Nissen article, there was an editorial and an editor comment that the results should be considered preliminary and interpreted with caution. Give me a break- the NEJM rushes this report to publication, hypes it big time, and asks us to interpret the results with caution. Don’t get me wrong, I LOVE the NEJM and have subscribed to it since 1965, but this was done poorly.

I almost forgot- what should people with diabetes do?

First, I wouldn’t start any patients on Avandia or any of the other glitazones at this time. There are many other drugs (those manufacturers are smiling today). In fact, most of my colleagues who are “expert” in the management in patients with type 2 diabetes, rarely if ever use the glitazones because of their known side effects: I find the vast majority of physicians who prescribe the glitazones and the newer drugs for the treatment of type 2 diabetes, are primary care physicians who learned about these drugs at a drug-company sponsored lecture or from their drug company rep, who provided samples (forgive me if I generalize to excess).

Where do we get our medical information?

One last thing- I am concerned that, increasingly, we (health-care professionals and the lay public) get most of our medical information from the media- TV ads and news reports. The news reports are of particular concern to me. I would be willing to bet that 90% of medical news reported in the media (including the New York Times) comes from only a few out of thousands of medical journals- The Journal of the American Medical Assoication, the NEJM, and Nature. Is it marketing by these journals or is it that the science/medical news journalists rely most heavily on these few journals? I don’t know, but it’s not healthy for any of us.

Yesterday, I received a telephone call from the mother of a young man who will turn 19 years old in about 10 days. The boy, who we will call Rick, has type 1 diabetes mellitus, diagnosed when he was about 10 years old. For a number of reasons, he has not done particularly well with his diabetes over the years, including many missed clinic appointments. Regardless, he is a pleasant, personable, and intelligent young man. He will graduate from high school in about 3 weeks. He wants to attend college but he has made no plans so far and does not know what he wants to study. I should add that he has had some drug problems and has just gotten out of a rehabilitation center.

Why did Rick’s mother call me?

Rick’s mother told me that Rick is now very focused on doing better with his diabetes and wants to see me in the next week or so, before his Medicaid coverage runs out (in my state, Missouri, Medicaid coverage for children is terminated on their 19th birthday). Rick lives with his mother. The parents are divorced and the father plays no role in Rick’s life, including financially. Rick’s mother has a full-time job, but no health insurance. So, in about 2 weeks, Rick will have no Medicaid coverage for his diabetes. So, what are his options?

First, he could try to get health insurance through one of the insurance carriers licensed in our state (e.g., Blue Cross/Blue Shield, United Health Care). That won’t work since he has a “pre-existing condition,” and is not eligible. He could get coverage through the state “high risk insurance pool,” a way for people like Rick to get health insurance. That won’t work given the cost which is about $800/month for a high deductible plan; neither Rick nor is mother have the resources to afford such a plan. I could lay out lots of other possible solutions, but I can assure you that none will work for Rick.

What if Rick had serious diabetes complications?

Quite a few years ago, I wrote an editorial to a medical article about the high prevalence and high costs of kidney failure in patients with diabetes. My editorial was entitled (as you might guess), “Is a pound of treatment better than an ounce of prevention?” As I recall, the results of the landmark Diabetes Control and Complications Trial, or “DCCT,” had just been published. The DCCT showed that diabetes complications (including kidney disease) could be prevented if the diabetes is well-controlled (we’ll come back to the DCCT in future entries). Anyway, in my editorial I tried to make the case for promoting excellent diabetes care “up front” to prevent the costly complications.

Rick’s dilemma

So, in about 10 days, Rick will have no means to pay for his costly diabetes supplies, let alone clinic visits and laboratory studies. I’ll do the math for you- the cost for his basic diabetes care is dramatically less than if he should develop serious diabetes complications, which he surely will unless he works to do well with his diabetes. But, Rick won’t even have the means to do well. Great system we have!

What am I going to do about this situation?

In a few days, I will see Rick in my clinic. I will try to help him develop strategies that will get his diabetes on track. I will encourage him to keep in close contact with me by telephone or e-mail over the next 1-2 months. I have looked into a free health clinic where Rick could go and even get some of his medications for free. He will need to apply; to qualify his mother’s income will need to be below a certain level- it will be a close call. The next available appointent is in about a month.
He could look for a job with health insurance- typically jobs with large companies that have health insurance for all employees without exclusions for “pre-existing conditions,” governmental agencies, hospitals, etc. He may have trouble given his drug history, but maybe not. I think full-time college is out for the moment, if he wants to do well with the diabetes (some colleges offer heatlh insurance to full-time students at very reasonable rates but one must have pre-existing insurance to qualify. Bummer.

The crazy thing is that if Rick has serious complications now, such that he has serious “functional limitations,” he could get coverage and an income to boot through the U.S. Supplemental Security Income program (SSI). Of course, if we just wait a few years, that will be a good option for Rick.

What am I trying to say?

What I have tried to explain is that our health-care system is not very good at facilitating optimal medical care for people with certain chronic medical conditions, such as diabetes who cannot obtain affordable health insurance. The end result is often dramatically greater costs (borne by all citizens with health insurance) to treat disease complications than would have been required to carry out high quality basic care of the condition. Diabetes is a great example since we know that all of the complications of this disorder are preventable.

I want to call another newsworthy report to your attention. In today’s New York Times (page A21), an article by Richard Perez-Pena detailed the results of a study released yesterday on the prevalence of diabetes in New York City. This study, started in 2004 by the New York City Department of Health and Mental Hygiene, found that about 1 in every 8 New Yorkers have diabetes and many more have “prediabetes,” a condition in which people have abnormally elevated blood sugars, but not high enough to earn a diagnosis of diabetes; prediabetes is a very high risk precursor to the “real deal.” Anyway, the data suggest that more than 100,000 New Yorkers have diagnosed diabetes that is “seriously out of control,” and more than 200,000 don’t even know they have the disease. The city health commissioner, Dr. Thomas R. Frieden put it bluntly: “This confirms that we as a society are doing a rotten job both preventing and treating diabetes.” Who could disagree?

Actually, the data are not a great surprise; we already know that the prevelance of type 2 diabetes in the U.S. is about 10%- much higher in certain ethnic groups. In people over 40, the prevalence is about 11%; in people over 60, it is more than 20%. Amazing stuff. We will come back to this subject later, when we discuss the obesity epidemic- oh, I forgot to say, virtually all of the people with type 2 diabetes are overweight. Sorry.

I do want to congratulate the New York City Department Of Health and Mental Hygiene for their impressive work in documenting the alarming state of diabetes in New York (and everywhere else in the U.S.).

The good news with this bad news is that right now on January 31, 2007, we can both dramatically decrease the prevalences of prediabetes and diabetes and improve diabetes care, once the condition is diagnosed, but only if we as a society decide it’s important enough to do (it is). Later, we’ll discuss how to do things better- I promise. What does any of this have to do with pediatric endocrinology? Glad you asked. We are seeing MUCH more type 2 diabetes in children these days (not much before the teen years), generally in the same families where parents and other adult relatives have diabetes too. Of course, the children with diabetes (and prediabetes) are overweight, just like the adults.

Coming soon, a discussion about the twin epidemics, type 2 diabetes mellitus and obesity.