Are SGLT2 Inhibitors a Bad Idea?

SGLT2 Inhibitors are the Latest Treatment for Adult Onset Diabetes. However, Many Treatment, Like Insulin, Have Done More Harm Than Good. Caution is Advised.

Brilliant basic science research continues its quest to understand human physiology. Pharmaceutical science continues its quest to cash in on the latest basic science discoveries. I want to illustrate this specifically with SGLT2Nephron inhibitors. In that setting I also want to ask what is the ethical duty of the medical profession towards those suffering with Adult Onset Diabetes Mellitus (AODM)?

SGLT2 inhibitors block the type 2 sodium-glucose-transport system in the kidneys. What the heck is that?

The kidneys serve as a passive filter, somewhat like cheesecloth, as an active pump emitting undesired chemicals in the urine and as an active pump holding onto presumably desirable chemicals. The kidneys are very good at actively holding onto glucose; it exchanges, spits out, sodium, in order to hold onto glucose. There are two such known systems, I bet you guessed, called SGLT1 and SGLT2.

In diabetes blood glucose can become high enough to exceed the capacity of the kidneys to hold onto glucose and then it escapes into the urine; called glycosuria. In Type I the threshold is about 150 mg/dl before the glucose escapes into the urine. In AODM the threshold can be even higher, much higher, so by using the SGLT2 inhibitors those with AODM more or less urinate out a lot of their glucose. It does seem odd, another blog post to discuss this, that the kidneys try even harder to hold onto glucose in AODM than in health or even Type I DM.

Those advocating the use of SGLT2 inhibitors point to water-weight loss, consequent, though temporary, lower blood pressure and other virtues. They minimize currently known side effects like ‘yeast’ infections in both men and women and confess that we don’t really know anything about long term consequences. What we do know is that blood glucose goes down. Analogies are made to mice models without, called ‘knock out mice,’ SGLT2 who seem to be doing alright; I mention this to give them their due for clever work looking at SGLT2 inhibitors. All and all from the basic science, pharmaceutical and clinical science perspective this is all very elegant work.

B11010370_f260ut is it a good idea for every doc on the block to be handing out SGLT2 inhibitors? At first blush it might seem that giving someone with AODM a new drug that lowers their glucose can only be helpful. In fact the argument goes something like this, taken from Medscape, a largely doc portal:

“According to the Center for Disease Control and Prevention, diabetes presents features of an epidemic: it is common, disabling and deadly. Approximately 25.8 million people in the USA (8.3% of the population) have been diagnosed with diabetes. It is the leading cause of blindness, kidney failure and non-traumatic foot amputation, and it has been reported as the seventh leading cause of death as listed on the US death certificates in 2007. It has been estimated that incase the current trend continue, one of three US adults will have diabetes by 2050. From the financial point of view, the total cost (direct and indirect) of diabetes in 2007 was $174 billion of which $116 billion was direct medical cost.”

OK, with that ringing in your ears, it seems urgent to find every single drug that ameliorates AODM and docs should be writing prescriptions for those drugs at the drop of the proverbial ‘hat.’

But wait. It is still common to prescribe injectable insulin for AODM even though, given alone, this has been shown to increase the risk of cancer by nearly 50%. It took years and the lives of many people before this was known and still it is common practice.

So, caution is in order with any new approach to an old disease. However even this is not my objection to using the SGLT2 inhibitors. I have an even more broadly-based objection.

In the words of a better, more persuasive writer, my objection would lead you to this conclusion: it is the ethical duty of the medical profession to always and everywhere advocate personal behavior and cultural trends which support people in overcoming AODM by the simple, powerful and effective expedients of better diet, better sleep and more, and more effective, exercise. My claim is few do this not merely from lack of will power but from the continuing misdirection of the medical and pharmaceutical communities that such a simple cure is impossible but for the supermen and women among us. This is not so; with the conviction that it is possible, and quantitative and reliable guidance, anyone can do it.

What say you?

  1 comment for “Are SGLT2 Inhibitors a Bad Idea?

  1. January 30, 2015 at 11:47 pm

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