The first of the oral medications that I want to talk about
are the secretagogues. Now secretagogues are the oldest
oral class in diabetes. They increase insulin secretion. It is
associated with weight gain and hypoglycemia however.
So there are some downsides to this particular medication.
Now the first generation secretagogues really aren't used anymore.
And I don't really encourage you to learn
too much about them at this point in time.
The second generation secretagogues are going to be the ones
that you will be asked about on your exams.
So it's important to know or at least recognize these names.
The third generation of insulin secretagogues are very much
coming into it's own forte in clinical practice.
And right now we use them perhaps 5 or 10% of the time but
I think in the future we'll start to see them being used much more often.
So how do secretagogues work? Well let's take a look at that
GLUT 2 glucose porter at the luminal surface of the cell membrane.
This glucose transporter moves glucose into the cell. Now the
glucose is going to be used for metabolism obviously.
And it eventually gets broken down and converted into ATP.
Now ATP is going to act on the potassium channel.
Now when the potassium channel closes, the cell is depolarized.
Sulfonlyurea drugs block and close and depolarize the cell membrane.
Now when you have a depolarized membrane, you are going to
have more calcium influx into that cell.
The depolarization opens up that calcium channel, and allows
lots of calcium to move in. So now, you have more calcium inside the cell.
When you have more calcium inside the cell, those calcium
ions can form bridges between the vesicles that contain insulin.
So you have, calcium mediated exocytosis of insulin. So you
have more insulin secretion. Now, if your beta cells aren't working,
and you're not making insulin in the first place,
secretagogues are not going to work.
Let's move on to the biguanides. Now the biguanides, are the
mainstay of diabetes treatment.
They are first line, they are the most important drugs, and
they are the most commonly used drugs.
The other beautiful thing about biguanides is that they're
cheap. So remember that they are first line therapy,
they are cheap, effective, and very safe. There is a couple
of advantages to the biguanides.
They actually work by increasing insulin sensitivity. So they
work really well with those type II diabetics.
And when you get out into clinical practice, you're gonna
realize that the type II diabetics are by far the majority
of the patients that we deal with.
The other nice thing about the biguanides, is that they
actually reduce endogeneous insulin production.
And the reason why that happens is because you don't need
as much, because the insulin is more efficient.
Remember that insulin itself has some negative properties to
it. So having hyperinsulinemia in diabetes is not necessarily
a good thing.
It actually prevents the development of diabetes in patients
who are prone to it. So if you have a person who has,
moderately elevated sugars or impaired fasting glucose, and
you put them on metformin or other biguanides,
you actually reduce the chance that they will progress to
full blown diabetes in the future.
It is also used to restore fertility in anovulatory women.
So it is used in infertility treatments.
Let's talk about side effects. Now normally when I talk about
side effects, I talk about bad things that happen with drugs,
but I want to mention something that's really important with
the biguanides and it's, they do not cause hypoglycemia.
And this is an important distinction between biguanides and
other drugs. And in fact, hypoglycemia is a really bad thing in diabetes.
I always say to my patients that hyperglycemia kills in the
long term and hypoglycemia kills in the short run.
So it's important that we avoid hypoglycemia in our patients,
because patients who become hypoglycemic,
are actually at increased risk of developing arrhythmia.
So, biguanides do not cause hypoglycemia.
Now you can get lactic acidosis in certain patients,
particularly those who have renal disease, liver disease
and respiratory disease.