Thursday, November 29, 2007

Most Diabetes Clinical Trials Ignore Everything But Blood Sugar Control

For those of you who read Diabetes Health, you may have caught a recent write-up that indicated a commentary article published in the September 29, 2007 edition of The Lancet entitled "Patient-important outcomes in diabetes—time for consensus" in which the authors, largely from the Mayo Clinic, report that a majority of diabetes clinical trials in the U.S. ignore virtually everything except glycemic control. In the article, the authors wrote:

"Unfortunately, HbA1c loses its validity as a surrogate marker when patients have a constellation of metabolic abnormalities, when the most common complications are macrovascular, and when the treatments have multiple poorly understood effects."

Obviously, that was a not-so-subtle reference recent issues with the GlaxoSmithKline drug Avandia. Unfortunately, the reason for this is driven largely by the U.S. Food and Drug Administration (FDA) and other drug regulatory agencies, which really consider nothing else except glycemic control when evaluating new diabetes treatments. But the same applies to type 1 diabetes treatments, too.

For example, Dr. Steven Edelman, assistant professor of medicine at the University of California San Diego School of Medicine, wrote to the FDA in 2003 in support of Symlin's New Drug Application, "Our country has tunnel vision in that a drug is judged on its ability to drop the A1c and is blinded to the many other important aspects that a therapeutic agent for diabetes can offer."

Even if a patient's A1c doesn't shift, most diabetes medicines (including insulin) still have major problems that impact patients' overall quality of life as well as compliance, including unpredictable glucose swings throughout the day, hypoglycemia, weight gain, gastrointestinal issues, and general frustration with the lack of precision in trying to actually control their blood glucose levels.

At least now we have credible, peer-reviewed data to quantify just how widespread this problem actually is, which happened to be published in the world's oldest peer-reviewed medical journal. According to the Mayo Clinic, only 1 in 5 trials measures the effect of drugs on quality of life and risk of complications. As Diabetes Health summarized, "The trials can be smaller, shorter, and cheaper without considering these factors, but they're not necessarily better for patients."

According to the commentary by Victor Montori, MD, of the Mayo Clinic, "the apparent benefits of these trials are a mirage….Patients and society may end up paying dearly for medications that cause more harm than good…. The medical community should insist that we invest the resources needed to do trials that ascertain the effect of interventions on patient-important outcomes."

The commentary concluded: "A conscientious patient with diabetes would like to choose drugs that maximize benefit (reduce complications) and minimize burden (route of administration, need for self-monitoring, cost), side-effects (weight gain), and efficacy failure (hypoglycemia)."

I happened to find a copy of The Lancet article on the Internet (normally, they charge $30) so you may access the Lancet commentary, including a truly lovely photograph of a foot ulcer here. Happy reading!


BetterCell said...

Thanks for the PDF File Scott.
In reference to what you wrote, many of us w/E1DM and who read as well as stay in touch with medical related Diabetes information, have known about the short-comings for years related to studies and "new medications" being made available.
It is sad that someone after all this Time has recognized, that Diabetes is about more things than numbers.

Scott S said...

I hope it becomes recognized by the FDA, otherwise the Lancet article would be a waste of time and space! Perhaps wider recognition will follow now that it has been published in one of the world's most respected medical journals.

Jenny said...


Not to mention the many NON diabetes drug that either cause obesity in people who were normal weight to start with, like the SSRIs or that cause frank diabetes, like the atypical antipsychotics.

These side effects were deemed acceptable and never mentioned to the people who take these drugs.

The so called "obesity epidemic" correlates very closely to the surge in SSRI antidepressant prescriptions. These drugs are known to cause weight gain.

Anonymous said...

Praise Dr. Montori for holding true to the Hippocratic Oath. Too often doctors forget to pay attention to their patients and the "patient-important outcomes". I suppose the treats dangled before them are a better incentive to sit, speak, and rollover when Big Pharma says so. I guess the business of medicine got too hard with the flurry of new drugs coming to market. To practice and prescribe to the best of my ability for the good of my patients, and to try to avoid harming them is too hard these days. Bad boo-boo!

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