The dog that did not bark

Sorry that I have been a bit quiet recently. Just been finishing off my latest book ‘The dangerous book for grown-ups.‘ [Plug]. Anyway, I most amused to see the latest headline from a study that appeared in my inbox. I felt I had to comment.

‘Onglyza offers unparalleled confidence in a broad range of patients with Type 2 diabetes, delivering effective glycaemic control, without the worry of increased risk of CV events.’ This headline was from a site called MDLinx that pushes stuff at me – whether I want it to or not. Actually I did subscribe, as I am always interested in what the pharmaceutical industry is saying about itself.

Onglyza by the way is one a range of new drugs designed to lower blood sugar levels in diabetes. It works in a complicated fashion. However, the bottom line is that is increases insulin release – mainly after mealtimes. Onglyza also goes by the generic name saxagliptin.

Anyway, to return to the main point here. We have this wonderfully positive headline about a new trial on Onglyza, and what could be wrong with that, you may ask yourself? Well, once upon a time, it was assumed that if you lowered that blood sugar you would also reduce the risk of cardiovascular disease. Heart attacks and strokes mainly. This was because a raised blood sugar (or type II diabetes) is seen a very strong risk factor of cardiovascular disease.

Which means that you would kind of expect that if you lowered blood sugar using Onglyza, you might also see a reduction in heart attacks and strokes. instead we have a headline proudly announcing that doctors need not worry about Onglyza increasing cardiovascular risk. My but life does move on.

So what the bloody hell does it do then, exactly? Well, there is much concern that it might increase the risk of pancreatic cancer.  Anything more? Well, here from Wikipedia:

In February 2012, Bristol-Myers/Astra Zeneca distributed additional safety information on saxagliptin use in South Africa. The package insert is to be edited for South Africa. Contraindications will now include a history of sensitivity to saxagliptin (or another DPP4 inhibitor) as well as pancreatitis. Spontaneously-reported adverse events in South Africa have included anaphylaxis, angioedema and acute pancreatitis.

In a cardiovascular outcomes trial, saxagliptin treatment let to a small but statistically significant increase in the risk of being hospitalized for heart failure.

Blimey, is there nothing this drug cannot do? Well, one thing it does not do, hooray, is that it does not actually increase the risk of cardiovascular disease. Just as well really, otherwise every effect that Onglyza has would seem to be completely negative. Heart failure, pancreatitis, possibly even pancreatic cancer.

We have reached an interesting point in drug development when the fact that a drug designed to prevent a disease (CV disease) is hailed for not causing an increase in that very disease. Has this really become the limit of our ambitions.

Having thought about this for a while I decided to create my new generic headline that pharmaceutical companies can feel free to use if they wish. Are there no limits to my generosity?

‘A groundbreaking study has found that (insert name of drug here) does not kill people from the disease it is supposed to be preventing. Internationally famous opinion leader (insert name of opinion leader here) says this is a landmark study and strongly recommends that (insert name of drug here) should become the drug of choice for (insert name of disease here)



23 thoughts on “The dog that did not bark

      1. Kevin O'Connell

        But isn’t that an AVK? Therefore vitamin K2 is in short supply. Therefore Matrix GLA protein doesn’t get (sufficiently) carboxylated. Therefore calcium doesn’t get (sufficiently) removed from soft tissue. Therefore… gulp! Or am I wrong?

        Certainly, when I found out about that, I hastened to persuade my cardiologist that I no longer needed to take an AVK. (Fortunately, he did not propose one of the new anti-coagulants).

  1. Spokes

    ‘The dangerous book for grown-ups.’ I am intrigued. Probably because of all that intriganol I’m on for disintriguement, my gp prescribed it after reading me this:

    ‘A groundbreaking study has found that Intriganol does not kill people from the disease it is supposed to be preventing. Internationally famous opinion leader Dr I.Drivealexus says this is a landmark study and strongly recommends that Intriganol should become the drug of choice for Intrigue insufficiency‘

    But I’m worried that the drug might be causing intense curiosity, and experiments in cats seem to suggest this is a bad idea. Although pharma reps are saying that cat’s in their experiments usually finish the course with eight lives, a significant improvement over a cat’s typical one life. It’s all so confusing.

  2. Janet

    This report seems to have an eerie similarity to those new anticoagulants recently approved for a-fib stroke prevention. (you mentioned warfarin and really nailed this one).

    For $4 one can have warfarin (the gold standard in preventing clots from moving from the heart to the brain and causing an ischemic stroke), albeit with the possibility of causing unwanted bleeding elsewhere but it has an antidote. This one comes with the responsibility of monitoring the dose with lab work to determine if the dose is compatible for the diagnosis and the patient and some attention to diet interactions.

    For $400 one can have one of the novel oral anticoagulants (NOAC) that are “non-inferior” to warfarin, has the same effect of causing unwanted bleeding, there is no test to know how well and how much it is working (if at all), and there is no way to reverse those pesky unwanted side effects of it (uncontrolled hemorrhage in the brain, gut, or anywhere else in the body). There is, however, the freedom from knowing if or how it is working with those tiresome lab values and the freedom to eat all the broccoli, spinach, and sprouts one actually wants to eat. This $400 option offers a decrease in the chance of intracranial hemorrhage death of about 0.7% with an increased chance of gut hemorrhage. The only instructions with the new drugs is “don’t hemorrhage because we can’t stop it until the drug wears off in about 12 or so hours”. But the real news is that they are NON-INFERIOR to warfarin.

    Who do you think came up with the recommendation that one of the high-$$$$ NOACs are the best choice for anticoagulation in a-fib patients? Looks to me like these drugs are the recommendation of the drug companies who make them. Of course I am just as surprised as you are!!!!

    Is this another dog that doesn’t bark, in the yard next to the diabetes breakthrough dogs?

  3. David Bailey

    I’d like to ask Dr Kendrick if the whole fat/cholesterol/statins mess is typical of the rest of modern medical science, or very exceptional. Put another way, what fraction of medical interventions are definitely useful?

    1. Stephen Rhodes

      It is rather sad that we have come to the point where the safest course of action when taking medical advice is to adopt a ‘weak Paxman’, not quite going so far as he does with politicians, but some of the way.
      The dental profession now treats as little as is necessary, my mouth is a micro Minimata compared to my children’s – thank goodness.
      But it is not all negative and as a guide, go with advice that appears the most minimal and least invasive, and always ask whether less might be more.
      Personally, I regret that so much is now wrong with nutritional advice largely as a result of a collective amnesia but partly as a result of a desire to push profitable pharmacological correctives instead of free dietary advice that most GPs are unqualified to give.

    2. David Bailey

      I think I have found the answer to my question – a little GOOGLing reveals that his new book, “The dangerous book for grown-ups.” is about exactly that issue! I look forward to reading it!

  4. Chris


    I’ll be placing an advance order.

    I feel the potential market for a sequel is growing, ‘Whatever happened to wellness?’

  5. Stacie

    Kevin-does AVK mean anti-Vitamin K?. I think you have a very valid point. You could also take fish oil, arginine, and hawthorn to prevent blood clots. In the end, when all is said and done, I think we will find that most diseases are a result of nutrient deficiencies caused by food processing, CAFOS, etc. Vitamin K2 is a perfect example. It is vital to healthy arteries, yet how many people are eating grass-fed beef, raw milk and cheese, etc..? How many people have even heard of Vitamin K2? If the conversation comes up, I tell my friends to ditch the calcium supplements and take K2.

    1. Kevin O'Connell

      Stacie, yes, AVK = anti-vitamin-K. I do take some fish oil & hawthorn + lots of butter & cheese (mostly local = grass-fed = lots of K2).

    1. Spokey

      Seconded. Seriously some of the things I’ve read since becoming aware of this topic.
      I was trying to come up with an analogy to the statins thing, mainly because you get the ‘many wrongs make a right’ statistical argument lobbed at you when discussing it, and it’s rather had to sink because you have to do a lot of work to make your case, much more work than “They’re a recognised body with lots of data, therefore it’s legit.” Here’s my analogy:

      The laws of physics suggest dropping a large rock on your foot will lead to broken toes, so why on Earth would anyone with that knowledge not be suspicious of a company selling large expensive rocks claiming to have a study showing that the correlation between dropped rocks and smashed feet didn’t reach statistical significance?
      Wouldn’t you at least have questions about why that would be? Why in situations like this, do people just trust secondhand data over laws of cause and effect? And why is the very idea of causality often viewed with such disdain by institutions who you might hope had the firmest grip on it?

      Perhaps I should just lead with, “Because I believe in causality more than bankrolled statisticians.” It’s exasperating, I am exasperated.

  6. Mark John

    The discussion re Warfarin and K2 inhibition is very valid.
    I recently saw our doctor with a female relative and the doctor prescribed a vitamin D and calcium combination (Adcal) for osteoporosis – 400IU twice a day of D3 which is hardly going to touch the sides in the sunshine scarce UK. I asked about the “Calcium Paradox” and also supplementing with vitamin K2, adding that the warfarin the patient’s on is antagonistic to K2. The doctor didn’t know what K2 was or did. Surely, surely, surely a GP should have knowledge of the studies which were succinctly summarised by Kevin O’Connell:

    “But isn’t that an [warfarin] AVK? Therefore vitamin K2 is in short supply. Therefore Matrix GLA protein doesn’t get (sufficiently) carboxylated. Therefore calcium doesn’t get (sufficiently) removed from soft tissue.”

    Re lack of knowledge around vitamin K2, the medical profession has probably been doing their female patients a disservice. Doctors commonly recommend a calcium supplement to their peri-menopausal, menopausal, or post-menopausal patients, just like I experienced with our GP and Adcal.

    Well, without vitamin K2 to properly direct or “usher” each of these nutrients where they belong (the bones), the calcium from both supplements instead travels to the cardiovascular system and the kidneys.

    Calcium buildup in the cardiovascular system leads to hardening of the arteries and can also cause direct problems with the heart muscle itself. Calcium buildup in the kidneys leads to kidney stones – a very painful condition that no one should ever have to suffer from.

    I would hazard a guess that if a person is taking vitamin K2 along with their vitamin D3 maintaining a 100-150 nmol/L serum level, there’s a good likelihood that they are getting sufficient calcium directed to the bones, and may not need additional calcium supplementation other than what they are are getting in their diet.

    Which leads me back to warfarin doing any good. It does “thin the blood” but equally, aren’t there better (more natural) ways that this can be done? If it ain’t good for the rats then is it really good for humans?

    1. Spokey

      Vitamin E has some blood thinning properties too doesn’t it? I think I read somewhere that K2 and vitamin E are antagonistic to each other as well, that is an excess of one can lead to a lack of the other.

  7. Phyllis Mueller

    Jenny Ruhl ( has written about an association between DPP4 inhibitors and melanoma. I started researching this link after a friend with type 2 diabetes developed melanoma and quickly died. I knew he was taking a diabetes drug and a statin but assumed the diabetes drug was metformin because metformin is so commonly prescribed. Now I suspect he was taking one of the newer drugs, a DPP4 inhibitor.

    1. Spokes

      I’m sorry to hear about your friend. I think two deaths in my family were connected with pharmaceutical compounds. Does it make you as angry as it make me to think this can happen in today’s enlightened times?

      I saw someone suffer both diabetes and serotonin syndromes due to psychotropic medications (the later killed themselves, but their quality of life was so atrocious at that point as upset as I was, I wasn’t surprised) and now I can’t really rule out statins connection to a death related to ‘atypical’ early onset dementia. Probably someone has a study that can show these were just placebo effects.

      1. Professor Göran Sjöberg

        What you say perfectly fits into my present view on almost all parts of the medical establishment.

        If you want some scary reading about the money cranking business which is corrupting most science about our mental health I can recommend the book I am just now reading: “MAD IN AMERICA” by Robert Whitaker.


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