Great White Lies

Editorial note: this post is by Dee Mangin

…. just when you were looking at pancreatic cancer on Januvia and Byetta.

Sugar sugar: Less is not more

Most people with diabetes now have type 2 diabetes. But for most people the high blood sugar called type 2 diabetes is not a disease. It is a risk factor. Just like blood pressure and cholesterol, the person sitting next to you with a higher blood sugar level than you is unlikely to notice a thing and neither are you.

High blood sugars won’t kill rapidly like diabetes does. Very severely raised blood sugars over a prolonged period can raise the risk of heart attacks or strokes just as very high blood pressure or cholesterol levels can in some people. Very severely raised blood sugars can lead to thirst, hunger and infections but very few people with type 2 diabetes experience this. For most people type 2 diabetes is a disease of numbers not of symptoms. For most people there is no good evidence that treating these numbers with the latest diabetes drug improves health.

Aiming for normal?

It might seem obvious to make the blood sugar level of young fit ‘normal’ people the target for treatment – but lowering the sugars of those with type 2 diabetes too much – aiming for ‘normal’ causes more harm than good in type 2 diabetes. More people die rather than less.

But aiming for ever lower blood sugar levels makes it possible to diagnose more people as diabetic and use more drugs which is good for business. This has been an easy message to sell to doctors and patients who understand type 1 diabetes and the benefits of the ‘tight control’ of blood sugar in this disease.

In type 2 diabetes the eye in the treatment game is well off the ball. Treatment is nothing to do with glycaemia but everything to do with subsequent disease. Unlike type 1 diabetes the two are not necessarily connected, yet the messages given to patients with type 2 diabetes act as though they are.

A large part of the rationale given for treating raised blood sugars is to prevent heart attacks and other vascular disease. Avandia and other drugs however have shown that you can reduce glycaemia but increase heart attacks at the same time.

The FDA response to the increased risk of heart attacks with Avandia was bizarre. Rather than requiring a demonstration of reduced heart attacks they set a threshold for an acceptable increase in heart attacks for new diabetes drugs that was more than any hoped-for benefit in reducing heart attacks from treatment.

Effect of these drugs is ‘modest’ at best

Studies of the newer drugs to help with the epidemic of diabetes the new drugs have failed to show they reduce the risk of heart attacks, strokes or vascular disease. None of these drugs can show they do any more than reduce blood sugars, and they don’t do this very well. The best that is said of the effect is that it is ‘modest’.

But there’s an old kid on the block – metformin. Metformin was first described by 2 Irish chemists, Werner and Bell, in 1922. It vanished from sight almost immediately, likely in the wash of the miracle of insulin which was discovered by two Canadians from the University of Toronto – Banting and Best – in the same year. Metformin was not a treatment for type 1 diabetes where the pancreas is unable to make insulin. Rather than pushing the pancreas to produce more insulin like the other agents for type 2 diabetes do, metformin acts by making the body’s cells more sensitive to the insulin the pancreas is already producing.

Unusually among drugs to treat type 2 diabetes, metformin makes a difference to things that matter to patients and not just their numbers. It reduces illness and improves lifespan. In contrast the New Drugs for diabetes have not lived up to the promise of insulin and metformin and to an extent glibenclamide, though unlike metformin, glibenclamide causes hypoglycaemia.

The only effect the other diabetes drugs have is on the blood sugar levels. None have proven health benefits in terms of the things that matter to patients. All have risks – some of them lethal. But this has not stopped companies peddling them to ever larger proportions of the well population – and as add ons to other drugs if blood sugar targets aren’t being met.

‘The extent of the long term risks are still unknown’

These days if your blood sugar levels aren’t low enough on one drug, you will be put on another and perhaps several others. In some trials where these newer drugs are added to the old, the number of problems with hypoglycaemia is higher and there is insufficient data from these brief trials on their long term safety to know how much of a problem this is – or to know how this will play out away from the highly controlled world of the partial brief statistical lives of trial patients to the real lives of patients using these drugs long term.

Low blood sugar – the great white

Check out the RxISK figures for low blood sugar for these newer drugs – hypoglycaemia, hypoglycaemic seizures and coma. These are almost certainly heavily under-reported because low blood sugar on these drugs doesn’t seem a problem – why report what treatment is aimed at doing? Except, low blood sugars are the Great White lurking in the Deep of type 2 diabetes. Low blood sugar – hypoglycemia – causes brain damage. Brain damage matters to patients. Despite the certain underreporting of hypoglycaemia the reports for each of these drugs are heading for 1000.

Pure white and deadly?

Just like blood pressure and cholesterol, glycaemia – sugar – is not a poison. It is essential for bodies and brains to function properly. Having too little is not a Good Thing. It is a Bad Thing.

While there can be immediate and severe effects of hypoglycaemia, there is also a striking association between hypoglycaemia and long term brain damage in type 2 diabetes that is not present in type 1 diabetes. A history of hypoglycaemia does not seem to increase the risk for later dementia in type 1 diabetes, but in the older population who get type 2 diabetes, the risk of dementia is increased after even a single serious hypo.

The more hypos the greater the risk of brain damage and dementia. For a patient with type 2 diabetes who is having hypoglycaemic attacks on their treatment, the risk of dementia goes up every year.

Where’s the sugar

Tombstone Arizona – In the Gunfight at the OK Corrall there were two competing stories about what was going on from two gangs – the lawmen and the cowboys. A key piece of evidence in the arrest of Frank Stilwell, one of the cowboy gang, was a witness overhearing one of the masked robbers holding up a stagecoach calling the money “Sugar”.

There’s a lot of Sugar in these new drugs for treating the diabetes epidemic. Unlike metformin, the only known effect these new drugs have is on glycaemia. Unlike metformin they induce a range of other lethal adverse effects as well as hypoglyacaemia. Unlike metformin they come with no long term safety data. Unlike metformin, they are not on the WHO essential drugs list.

This is the Great White Lie you need to watch out for.

Illustration: Sweet Lies, © 2013 created by Billiam James