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Wednesday, 29 September 2010

More Drugs for Diabete's - Back to the Future?

Way back in the mists of time, chemists discovered a glycoside compound from the bark of apple trees that had a profound effect on glucose disposal in Diabetics. This extract, called Phlorizin, brought about glucosuria, which is the excretion of glucose in the urine. It also to some extent also caused polyuria (excessive urination). As these are often symptoms of  Diabetes itself, and as it was only 1835, it took a while for it to be viewed as anything that could be useful. As time went by experiments were undertaken to find a use but it was not until the 1970's that the mechanism of the compound was discovered and named. Sodium-Glucose Co Transporter-2  inhibitor (SGLT2)  is what it became and is the current theme of most research, for yet another drug for Diabetes.

I say yet another, because rather than using the original compound, which was in fact poorly absorbed in the gastro-intestinal tract, 'Big Pharma' needed to come up with a better 'mousetrap' in the form of a synthetic compound that could be patented, so that money could be made. Frankly, I find it a little alarming as the way it works is to inhibit the capability of the kidneys to 'save' glucose from being excreted in the urine. This a process discovered, that the kidneys perform, to conserve vital energy in the body and functions at a certain level. In Diabetics with high circulating glucose in the blood, the kidneys filter out the excess and do not conserve it all, as with normal humans, hence both glucosuria and polyuria are symptomatic in the Diabetic with low level control of hyperglycemia. What these new experimental drugs aim to achieve, is to enhance this phenomena, outwith the normal kidney function, so that the process 'kicks in' at lower levels of concentration. It does this by inhibiting SGLT2 in the kidneys.

 Astra-Zenica are conducting trials of their contribution to this wonderful idea at present; it is called  Dapaglifozin and is being developed in conjunction with Bristol-Myers Squib.What is important is the unintended consequences that may ensue from this, and the effect it may have on kidney function in the longer term. These may be obvious to many Diabetics with a grasp of their problems and the primary one is the enhancement of urinary glucose. All Diabetics are prone to urinary tract infections and genital fungal infections. This is largely because of the high glucose content of their urine, as bacteria and fungi feed on this. Low levels of glucose and acid urine inhibit this but Diabetics struggle to maintain this and, as a consequence get this type of infection and use antibiotics regularly as a result. This of course adds to the problems most already have and exposes them to long term or repeated incidents of UTI's for which ever more drugs are prescribed adding to the polypharma to which they are all subjected. To expose them to even more risk in this area seems somewhat counter productive.

In addition these drugs thus far have not displayed a great deal of success and are viewed very much as an 'add-on' protocol, for use with other hypoglycemic agents, such as metformin. They do enhance the performance of of these agents and lower HbA1c a little, but nothing startling. They also do enhance weight loss to a small extent, which is usually a good thing for a Diabetic, but, is it not about time, that science stopped its constant search, for a fix for something that is easy to stop. Reduce the glucose level at source, by stopping eating carbohydrates to any extent and Diabetics ease the burden on their already overburdened pancreas, and both the need or at least the volume of drugs needed is reduced or even eliminated.Of course that presents a problem for healthcare and especially 'Big Pharma'. So much money is at stake, both for them and for the NHS, which spends in excess of 10% of it's entire budget on Diabetics. The gravy train would halt and quite a few employees would no longer be needed. Turkeys voting for Christmas, I think not!

It also goes to show the panic in the Industry at the moment to come up with new ideas for drugs because patents are fast expiring and little is in the pipeline. There has been nothing of any significance, discovered  in Medicine in nearly twenty years, except more 'me too' drugs or new strains of the old one's. So they are turning once again to the old favourites such as cancer or diabetes. They've peddled useless or near useless and dangerous drugs to these cohorts for years, without any glimmer of a cure and it's costing them billions in compensation for some, such as Avandia, the cost of which has virtually wiped out GlaxoSmithKlines profits for the whole of the last year. Makes your heart bleed does it not?

It would be nice for a change to see research being directed at a cure, for some of these ailments or at least some acknowledgement that lifestyle changes can be just as effective as taking a store cupboard full of dangerous and often self-defeating drugs. Perhaps that is asking for the impossible.

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