Gettysburg Medical Center
 The Clinical View
 by P.E. Hoffsten, MD
 10 May 2006

DIABETES MELLITUS – III:  EXENATIDE, A NEW DIABETIC MEDICATION

            I never cease to be amazed at how our medications are found and developed.  In the early 1990’s, researchers discovered a hormone that our intestines secrete when we eat.  This hormone was called GLP-1 and had the magical properties of making the person more sensitive to the insulin that they already have, of growing more insulin-secreting cells, of slowing the rate at which the stomach empties, and inhibiting the hunger centers of the brain so that the person ate less.  While it would be wonderful if we could provide this hormone as a pill or an injectable medication, that didn’t seem practical.  It turned out that GLP-1 is removed from the blood in about 4 minutes after it is injected and trying to inject something every 4 minutes really isn’t going to work.  But then some of these scientist types who work on things for reasons we don’t really understand, discovered something that looked an awful like GLP-1 in Gila monster poison.  Why the heck gala monster poison would have a hormone that our stomachs make is a mystery to me.  But none-the-less, it was there.  It turned out that the Gila monster poison lasted much longer than the natural hormone that our bodies had.  As you might imagine, this interested the research scientists at the drug companies and pretty soon they had developed something that lasted a long time like the gila monster poison, but wasn’t poisonous for us.  In addition and most importantly, the hormone developed by the drug companies had a long half-life so it only had to be injected only twice a day.  By 2004, a series of clinical trials had been carried out showing out that the new hormone called exenatide (Byetta) had five therapeutic advantages making it worthwhile and safe.  The FDA approved it for general use in April 2005.

            The five advantages of exenatide include:

            1.  It slows gastric emptying thereby avoiding the overload of the blood stream with carbohydrates that get digested through the stomach too quickly.

            2.  It acts on the central nervous system to decrease hunger and promotes weight loss.  On the average, people taking the recommended dose of the drug lost six pounds in a seven-month period of observation.  Note this was done without effort or direction.  It was simply a fringe benefit that this medication provided.

            3.  The drug was associated with a 0.8 to 1% drop in the Glycosylated Hemoglobin (A1C) that we use to measure how well diabetes is controlled.  Ideally, we want the Glycosylated Hemoglobin under 6%, in the normal range.

            4.  This hormone decreased the secretion of another hormone called glucagon.  Glucagon raises blood sugars, something that is not really useful in a diabetic.  By decreasing glucagon secretion, blood sugars come down.

            5.  Animal experiments have shown that exanatide actually leads to an increase in the growth of insulin-secreting cells.  This has not been shown in humans yet but presumably could reverse the loss of insulin-secretory capacity that is an intrinsic part of type II diabetes over time.

            Objections to the drug include it being an injectable.  One injects it twice a day before the morning and evening meal.  In some individuals, it may cause nausea.  This is especially true if the person doesn’t cut back on the amount that they eat.  Gastric emptying is slowed and if one overloads their stomach, nausea would be an expectation.  Third and most objectionable is that it costs about $175.00 a month, which gets very spendy if a person doesn’t have insurance coverage.

            Objections aside, the concept that this medication offers is a giant step forward in the treating of type II diabetes mellitus.  If this hormone really can be shown to enhance insulin- secreting cell growth and thereby prevent the deterioration of insulin-secretary capacity, a number of the severe disease effects of diabetes could be turned aside.  Secondly, if it really does contribute to weight loss through no effort on the person’s part, a tremendous advantage would have been achieved.  Every overweight person I have ever helped take care of has told me they thought there was something wrong with their hormones.  To this time, we have never figured out just what that might be but this could be a first step in saying “yes”, there is a hormone problem and we finally found one little piece of it.

            Being diabetic myself and wanting very much to avoid the degenerative affects of diabetes, I am trying exenatide myself at this time.  I will report back in six months and say whether I really think it is worth trying.  Up to the first week, I have had no trouble at all.