April 11, 2011

April Research Roundup

Here are the studies that caught my eye over the past month.

Metastudies fail to identify who sponsored the studies they are based on, allowing studies funded by drugmakers to appear to be unbiased research. If you've wondered why you are seeing so many metastudies--studies that pool data from many smaller studies--being published, this may be the explanation. As reported by researchers who analyzed the sponsorship of 29 metastudies based on 509 trials,
"Only 2 of the 29 meta-analyses even mentioned the issue of who funded the original drug trials, and even those 2 did it in very obscure places in the published articles," said Thombs, a psychologist and assistant professor in the Department of Psychiatry at McGill University. "Not one of the meta-analyses mentioned whether researchers who conducted the trials were employed by industry or personally received money from industry."
In addition,
The team identified 7 meta-analyses where every single drug trial included was paid for, at least in part, by the maker of the drug or had investigators linked financially to drug makers. In 6 of the 7 meta-analyses, however, there was no mention of who funded the drug trials.


1. Avandia Causes Significantly More Cardiovascular Problems and Deaths than Actos. This may be true, but this metastudy (sponsorships NOT revealed) failed to include a control group that was taking neither drug. It only compared those taking Avandia with those taking Actos. This gives the false impression that Actos is safe. In fact, since good data has shown that Actos causes heart failure in people who didn't originally have it, this was a seriously flawed study.

2. Actos seems to cause an increased risk of bladder cancer in those who take it for two years or more. Note the weaselly way that this result is reported. The definition of those "taking Actos" included people who only filled two prescriptions--i.e. the many who dropped it because of cost, ineffectiveness, and side effects. Among those who continued taking the drug cancer was more prevalent. Who do you think funded this study? You'll never know because the ADA's Diabetes Care's abstracts don't reveal the study's sponsorship.

A Kaiser study that controlled for a huge number of variables (possibly making the statistical results meaningless) found an elevated risk of melanoma among those who took Actos but downplayed this finding in the study's conclusion. Funding of this study is unknown.

3. Actos has a huge impact on preventing the progress to diabetes (i.e. blood sugar levels defined as "diabetic" on a fasting glucose or glucose tolerance test.) This is a high profile study published in the New England Journal of Medicine that got a ton of coveraage. To their credit, the NEJM, in its abstract, identifies the sponsor of this study--the makers of Actos. The drawbacks the study found were that Actos "was associated with significant weight gain and edema."

What is missing here is the information that other studies have found that exercise and dietary changes can produce a very similar decrease in progress to diabetes without any side effects and without Actos' risk of heart failure, macular edema (which can cause blindness)and permanent weight gain.


1. Missing Gene Suggests Rodents Aren't The Best Model For Diabetes Research As reported HERE:
All animals except people have a gene, Virtually all mammals produce specific sugar molecules that aid cells in interacting with their environment. That is, all except humans. Around 2 to 3 million years ago humans lost CMAH, a gene that codes for an enzyme that produces the sugar Neu5Gc.

To test the role of this gene, researchers compared two sets of mice. One group had a normal CMAH function and Neu5Gc production, the other group did not—just like humans. Both groups of mice were fed a diet that normally induces obesity and insulin resistance (metabolic syndrome), and both groups experienced these symptoms. However, only the mice missing the CMAH gene had lost the ability to produce insulin in the pancreas.
There are many other differences between mice and humans that make them a poor model for type 2 diabetes--most notably, the fact that most mice fed high fat diets develop diabetes while humans (for example, Inuit) fed the same diet do not.

2. Gut bacteria can control organ functions in mice--including liver glucose levels. What's interesting here is that we know there is an association between gut bacteria and obesity in humans, so it is possible this mouse finding is relevant. Are the trace amounts of antibiotics, pesticides and herbicides that are in our food and water supply changing our gut flora in ways that promote the growth of bacteria that contribute to diabetes?

3. Insulin releasing switch discovered. It's called "snapin" and it appears to play a significant role in stimulating beta cells to secrete insulin.


1. Strong evidence that antidepressants are causing thickening of carotid arteries (strongly associated with heart attacks). This study was presented at 2011 American College of Cardiology annual scientific session, New Orleans, and received NO play in the press--note that it is Business Week who picked up on it. This was an identical twin study where one twin was taking antidepressants and the other wasn't. The study authors found that "a twin taking an antidepressant had a greater intima-media thickness than a brother not taking the drugs." Given that SSRIs greatly increase insulin resistance this shouldn't be a shocker. Don't expect to hear any more about this as drug companies spend even MORE money marketing antidepressants than they do dangerous diabetes drugs and their advertising--and research--dollars affect media coverage.

2. Death from all causes and from heart attack associated with insulin stimulating drugs compared to metformin. This major study involving "All Danish residents >20 years, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years)" found the following drugs were as safe as Metformin: Prandin (repaglinide), and Diamicron (gliclazide, not sold in the U.S.).

All the other sulfonylurea drugs raised the risk of death, whether or not people had had a heart attack before taking them. The study concludes: "Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other I[nsulin]S[ecretagogues]s."



Heather said...

The missing gene in rodents information is very interesting! I wonder if the presence of CMAH helps explain the fabulous diabetes cure rates in mice and rats.

Jenny said...

CMAH is only one metabolism-related gene in rodents that works differently than it does in humans. There are many others. The "diabetic" rodents used in research are rodents whose high blood sugars are caused by genes that we KNOW aren't the ones that are found in HUMANS with diabetes.

Remember when there was all that excitement when the cure was found for the OB mouse that is the "model" for obesity? It turned out to be something that applied to two human families worldwide. The Type 2 rodent models aren't any more relevant.

I have blogged about this here.

Fresh Garden said...

That's informative and inspiring!
Thanks for sharing, I enjoyed the visit. ;D

patipaw said...

Jenny, everyone,
Hi. I wrote to you previously and got wonderful advice.

I am currently looking into my situation and would love your input.

I was prescribed Actos. I took one dose and went into congestive heart failure. I had no cardiac symptoms prior to taking Actos.

Now, being treated for my CHF, I am being told A. Actos does not cause heart failure, but merely aggravates what is already there and B. It is impossible for one dose to trigger CHF.

Can you give your thoughts, and point me towards documentation? I see some already here on Actos causing CHF, and will look into that.

Thanks so much


Jenny said...

Pati, I am so sorry to hear of the horrible experience you are having to deal with. No words are enough.

All I know about the TZD family of drugs and heart failure in people who didn't start out with it is on the page on http://bloodsugar101.com called Actos and Avandia: Dangerous Diabetes Drugs. As you can see there is a publication there that reports on the phenomenon.

But the drug companies pretty much brush the problems their drugs cause under the table and don't publish about how to deal with them. So it can be difficult to know what the best treatment is or whether the symptom you developed from the drug is really the same as a similar problem not caused by the drug.

I wish I had more information for you. Probably your best advice is to audition cardiologists until you find one who has more curiosity than most and is willing to work with you beyond just dishing out the textbook treatments. It may take seeing several to find the right one. people don't realize until they have a serious condition the range of talent to be found in so called specialists who, in my personal experience, range from the abysmally distructively dangerous to life saving.

Wishing you the best.