After its launch in the late 1950s, Upjohn’s Orinase (tolbutamide) became the first blockbuster hypoglycemic (blood sugar lowering) drug. Its success was born of failure. It wasn’t a replacement for insulin. Even if used early, it didn’t stop people from becoming insulin dependent. But attempts to create an early use market led to a focus on raised blood sugar levels and the creation of Type 2 Diabetes.
Diabetes is a rapidly fatal disease first recognized in antiquity. Insulin was one of the miracles of twentieth century medicine. With its discovery, people otherwise doomed to die were given a second chance. It didn’t just save lives it led to the very best medical teamwork between those with diabetes and those looking after them, as outlined in Annemarie Mol’s The Logic of Care.
The New Normal
The rebranding of raised blood sugar levels as a disease called diabetes was not a comparable blessing. This is not a disease. It is not diabetes. It won’t kill like diabetes. Severely raised blood sugars over a prolonged period can raise the risk of cardiovascular problems just as markedly raised blood pressure or cholesterol levels can, but clinical trials have shown again and again that except for Metformin the treatment is worse than the problem.
Sales of Orinase took off on the back of a marketing of raised blood sugar levels renamed Type 2 Diabetes. It is this that has given rise to the supposed epidemic of Diabetes we now have. An epidemic that is a major cash cow for the pharmaceutical industry.
The trick has been repeated across the board from anxiety states to bone thinning. The formula – rebrand some variation as a disease, have committees of experts regularly lower the acceptable blood sugar levels or bone densities so that an ever growing number of people can be diagnosed, condition people to think we have a problem through a dripfeed of press releases, hire some celebrity patrons; voila – a sales epidemic.
How do you stop a bandwagon?
In 2002 the Women’s Health Initiative Study of Hormone Replacement Therapy (HRT) managed to stop the bandwagon when it linked HRT to early deaths. But this hasn’t worked in the case of diabetes. In 1969, a major NIH study of treatments for Type 2 Diabetes caused consternation when it found that Orinase killed. Doctors protested – how could doing something as obviously sensible as lowering blood sugars be a bad thing? Later studies showed that it was indeed a Bad Thing. That lowering the sugars of those with higher than normal to ‘normal’ caused more harm than good.
Orinase had blazed the blockbuster trail and it was too valuable to Upjohn to give up lightly. They fought back, recruiting academics to contest the findings. Six years later when Jaws the first movie blockbuster was released, Orinase was still claiming its victims proving that Hollywood romance doesn’t apply to Great White Drugs feeding in healthcare waters.
The sequels to Jaws had almost no box office impact. But in the wake of Orinase, we have had even greater horrors from the even bigger Rezulin and Avandia blockbusters. Parke-Davis’ Rezulin (troglitazone) caused liver problems and death. It continued to be marketed direct to consumers in the US for years after its UK withdrawal. GlaxoSmithKline’s Avandia (rosiglitazone) caused heart problems and death, estimated in the tens of thousands.
The Cautionary Tale That Wasn’t
Now a new set of menaces stalks the waters – the Gliptins and the Incretins. The Gliptins are Sitagliptin, aka Merck’s Januvia, Janumet, and Juvisync, and Saxagliptin, aka Bristol Myers Squibb’s Onglyza and Kombiglyze. The Incretins are Exenatide, aka Amylin’s Bydureon and Lilly’s Byetta, and Novo-Nordisk’s Liraglutide, aka Victoza.
The script is more like The Cautionary Tale That Wasn’t as repetition increases rather than dulls these horrors. An innocent Chrissie Williams goes swimming and is savaged by something from below. Martin Brody (Roy Schneider), a sheriff in the Regulators Office, investigates. Amity Island’s successor to Mayor Vaughan leans on Brody. Brody then goes out of his way to obstruct Matt Hooper (the scientist – Richard Dreyfus) and Quint (the journalist – Robert Shaw) when they turn up.
From thalidomide through to Rezulin and the Gliptins, Quints have blazed the way. These are the hard bitten journalists like Morton Mintz for thalidomide, David Willman on Rezulin – out big story hunting. In the case of Avandia, the shark hunters were Panorama’s Shelley Jofre and Andy Bell. Jofre and Bell put the evidence of Study 329 in the public domain that led to fraud charges against GSK and the company agreeing to post its study results on the company website enabling Steve Nissen to discover the excess of cardiac problems on Avandia. Jofre is the nightmare that wakes Brody from sleep – a horror movie called Lips.
Through all these scenes, the drumbeat is the same – savaged bodies washed up on shore are discounted by Brody with lines akin to ‘there may be a signal but we don’t have conclusive evidence of a problem’. The half torso might have been because the poor girl swam into a boat’s propeller. More bodies washed up makes no difference. Observations like this don’t prove causality – you’re only noticing these things because of media reporting – young girls bodies wash up on the beaches round here the whole time. Going swimming puts them at increased risk of getting chopped in two – everyone knows that.
That Hooper guy he’s a scientologist or an expert witness hired by some lawyers – mark my words someone like that has just got to have something wrong with them, why else go round the place scaring people?
Look Quint, if you really want to test it out, we’d have to do a controlled trial like dump half the crew of the Indianapolis in shark infested waters to test out what’s going on.
But Mr Brody if the ships propeller is on, how would you be able to tell if this is down to sharks or not? Indianapolis, isn’t that where Byetta comes from?
The Byetta and Januvia stories are unfolding in the classic way. Quint in this case is Deborah Cohen in the BMJ. Hooper is Peter Butler and colleagues from UCLA who found evidence that these drugs cause cell proliferation triggering pancreatitis and cancers in both pancreas and thyroid glands. The science is pretty convincing – give the drug to animals and problems appeared, stop them and the problems clear up. Butler and his group have been ostracized.
The illusion of zero risk
Companies are so adept at handling these issues that they probably welcome the appearance of controversy – it increases sales. If you’re a doctor, come to Amity Island where there is more action on the beaches than anywhere else. Doctors, have we got the deal for you, your very own heated infinity pool – to give you the illusion you are in the water without any of the risks.
Over the top? Not a bit of it. In the case of Victoza, Liraglutide, there was very strong evidence that it could cause thyroid cancers. The regulators said they were prepared to allow the drug on the market with clear warnings which would of course make it a second line treatment. But warnings are gold-dust to companies and sales of Victoza hit blockbuster status soon after it came on the market. Just like Rezulin.
RxISK and You
But Quint and Hooper have a new weapon these days – the combination of RxISK and you.
1. Put Januvia or Sitagliptin, Onglyza or Saxagliptin, Byetta or Exenatide, Victoza or Liraglutide into the Search box on RxISK.org.
2. Go to the Established Side Effects tab and look at what the European Medicines Agency has to say about the side effect profile of each of these drugs. You’ll find pancreatitis is established as caused by each of them and that thyroid cancer is established for Victoza. This is data not available to Quint from any other source.
3. Go to the Reported Side Effects tab and click on All Side Effects (A-Z). Head for pancreatitis and pancreatic cancers as well as thyroid cancers and let your jaw drop – over 150 pancreatic cancers for Januvia and over a thousand cases of pancreatitis, with over 300 cases of pancreatic cancer for Byetta and over 4,000 cases of pancreatitis. And what’s this – 99 cases of thyroid cancer on Byetta?
4. Have a look at the Outcomes tab – how many deaths and hospitalizations?
5. Anticipating the brush off from Chief Brody certain to come your way – it is well known that diabetes causes pancreatitis and cancer so these reports prove nothing – check out the figures for pancreatitis and for cancer on Metformin, the most commonly used pill for lowering blood sugars, or for the previous blockbusters Avandia, now withdrawn, or Actos known to cause bladder cancer. You’ll see vastly less cases of pancreatitis or cancer and no thyroid cancers. Decide for yourself what chopped Chrissie Williams in half. Make up your own mind whether it’s safe to get back in the water – or whether the swim is worth it.
6. Help us track down the Shark. Get yourself a free RxISK report. Become one of the first to leave a RxISK story for these drugs. Between us we can build a HeatMap of where these problems are happening. If they’re happening in Martha’s Vineyard but not in North Carolina or Santa Monica this will give the Quints and Hoopers among us vital clues they’ve never had before when chasing sharks.
7. Take your RxISK report to your doctor. This will be like dropping a replica shark in the infinity pool – s/he will either react magnificently and become a key player in saving your life and that of others or you’ll see him in his true colors.
There are just two bits to the script we need to change to get things right for the new Spielberg thriller “Chemicals”. Martin Brody is never there when you need him. But Martine Brody is – someone’s wife, mother or daughter is invariably the one who refuses to act like nothing is wrong.
Someone who knows the Great White Lies are what you need to watch out for.
Spielberg’s skill in Jaws makes you look one way while the shark comes from behind. You are now looking closely at pancreatic and thyroid cancer, heart and liver failure. These are a high price to pay for people who didn’t have a disease to begin with.
But just as your pulse settles down…..
To be continued
Illustration: Meds: Pills that Kill, © 2013 created by Billiam James