Let's move on to incretin based therapies. Now before I talk
about the actual drugs, I want to talk about what incretins are.
So let's imagine you have an orange, and you
decide to eat it, and it goes into your stomach.
Well your stomach and your small bowel will release something
called incretins. These incretins act on the pancreas in two ways,
not one way but two ways. First, it will act on the beta cells
to actually increase the amount of insulin that you release into the body.
This decreases sugar levels. The other action is that it
works on alpha cells, to decrease glucagon secretion
and once again decrease sugar levels. Now this is an
important distinction between these drugs and other drugs.
Because the amount of alpha activity with the incretins is much
greater than the other medications or the other hormones.
A DPP4 is kind of like pacman because it goes in and eats
the incretins. So it's kind of our built in mechanism
to get rid of incretins once we no longer need them.
A DPP4 inhibitor, gets rid of pacman, right.
So DPP4 inhibitor now allows more incretins to do its job
for a longer time. So there is a couple of advantages
to this particular method. First, it's a very natural way
of affecting your systems because you're taking advantage
of internal systems to bring down the sugar, rather than say
artificially stimulating a cell to secrete insulin.
You're using incretins which are a naturally produced hormone
and you're letting them do their job for a longer time.
The other advantages that the DPP4 inhibitors almost have no
hypoglycemic risk. Now a GLP-1 analogue is an analogue of incretin.
So, DPP4 inhibitors and GLP-1 analogues are working through
the incretin pathway. They are slightly different
in terms of where they're acting on the
pathway but they both have the same effects.
Net effect, improved glucose control.
Now let's just take a look at the various drugs in each of
the drug class. If you notice and if you pay attention,
the DPP4 inhibitors end in -gliptin. So there's saxagliptin,
sitagliptin, linagliptin, and so on.
When you take a look at the GLP-1 analogues, they end in
-tide. So there is exenatide, liraglutide, etc.
Now, the other thing I want to mention is that the GLP-1
analogues are injections, whereas the DPP4 inhibitors are pills.
Now, the DPP4 inhibitors have a neutral weight effect and they're
very very well tolerated. They reduce the hemoglobin A1c by about 0.9 %
if you take all the trials and put them together. I should
mention though, that if you have an A1c that is 10.5,
the amount of reduction that you will get from your DPP4
inhibitor is going to be up to 2 %.
If your A1c is 7.5, the amount of reduction you're going to
get is probably 0.5 %.
So, your amount of reduction is proportional to where you're
starting. So the higher your starting A1c,
the more A1c reduction you are going to get. Generally speaking
these are once a day tablets. There are actually subcutaneous
forms that are given once a week however. They are rarely
associated with pancreatitis but the risk is there.
You can get occasional nasopharyngitis with these medications.
In terms of the GLP-1 analogues, these are the drugs that end
in -tide, they may actually cause weight loss.
So there is one study that looked at one of the GLP-1
analogues, and showed that 30 % of their patients, lost 3 kg
and they kept it off. It reduces hemoglobin A1c anywhere from between
0.9 % and 1.5 %. So as an average I just put down 1.3 %.
Remember as I said before these are injections, and these
medications are actually increased with more GI symptoms
than the DPP4 inhibitors. Be aware, that these medications
can be a associated with a very aggresive form of pancreatitis.
So monitor your patients closely when you
start them on these medications.