The parents of a 16 year old boy with type 1
diabetes visit the clinic for information
regarding a new injectable drug, exenatide that
only needs to be administered once a week.
They are quite excited about the prospect
of switching their son's medication
as he currently requires several
shots of insulin each day.
The boy's blood glucose levels are quite difficult to
control on his current regimen due to poor adherence.
His BMI is 19 (kg/m2)
He has had difficulty putting on
weight despite eating quite a bit.
Which of the following best describes
why it is not possible to start
the boy on a weekly dose of
exenatide instead of daily insulin?
Answer choice (A) - insulin production by the
pancreas is insufficient for exenatide to function.
Answer choice (B) - exenatide suppresses glucagon
secretion which increases the risk of hypoglycemia.
Answer choice (C) - suppression of appetite
makes it even harder for him to gain weight.
Answer choice (D) - exenatide is
contraindicated in children below 18 years
And answer choice (E) - gastric
emptying is inhibited by exenatide.
Now take a moment to come to the answer by
yourself before we go through it together.
Okay let's jump right in.
Let's review the question characteristics.
Now this is a pharmacology question.
We're reviewing a medication for diabetes and
seeing if it's applicable to the patient.
Now this is a 2-step question.
We first have to determine what type 1 diabetes
is with respect to the pathophysiology
and then determine if the drug in question
her is applicable for this disease.
And the stem is absolutely required to determine the patient's
clinical history to see if it's applicable to give him this drug.
Now let's walk through this question together.
Step 1 - we need to determine the reason
for hyperglycemia in type 1 diabetes.
And in type 1 diabetes, the pancreas produces little or no insulin
due to destruction of beta cells in the islets of Langerhans.
Now that's how type 1 diabetes works.
Now for step 2, we need to determine the mechanism of action
of exenatide and its suitability for type 1 diabetes.
Now, exenatide is a glucagon-like peptide-1 receptor
agonist or what's also called a GLP-1 receptor agonist.
Now let's review how this works by looking at our image,
where GLP-1 therapeitic mechanism of action is reviewed.
Now looking at our image, we see that food is
consumed and goes through the small intestine.
And in the small intestine, food stimulate
the small intestine to secrete GLP-1,
and then GLP-1 actually
stimulates the pancreas.
And doing so, GLP-1 stimulates
the pancreas to release insulin,
it also suppresses glucagon secretion
and gastric emptying is slowed.
Now, if we have a GLP-1 analog such as
exanetide, it mimics the action of GLP-1
and then whenever food is consumed, it will cause
the stimulation of the pancreas to release insulin.
And that's how these GLP-1
analogs work such as exanetide.
Now let's go back to our question to see if
this information helps us determine the answer.
Now, exanetide increases insulin secretion
from the pancreas in response to meals,
and thus exanetide actually is indicated
in type 2 diabetics but not type 1.
And thus exanetide is not suitable for type
1 diabetics as the few remaining beta cells
in type 1 diabetes are
already maximally stimulated
and providing such medication as the GLP-1
analog will provide no further benefit.
And also, exanetide generally suppresses
appetite leading to weight loss
with which further would not be in
the best interest of this patient.
Thus the correct answer is answer choice (A) -
insulin production by the pancreas is insufficient
for the exanetide to function and thus
is not appropriate for this patient.
Now let's discuss some high-yield facts regarding
type 1 diabetes and GLP-1 receptor agonists.
Now type 1 diabetes occurs when the
pancreas produces little or no insulin
due to the destruction of beta
cells in the islets of Langerhans.
The destruction of beta cells is thought
to be due to an autoimmune mechanism
with some type of genetic predisposition.
The treatment of choice in type 1 diabetics
is insulin as few remaining beta cells
are already functioning at maximal
capacity and cannot be further stimulated.
So type 1 diabetics lack it
and so we give them insulin.
Now GLP-1 receptor agonist, that's glucagon-like peptide 1
receptor agonist to a group of what's called incretin mimetics.
Now GLP-1 receptor agonist increase
insulin secretion from the pancreas
and decrease glucagon secretion by
the liver in response to meals.
Now GLP-1 receptor agonist are indicated for type 2
diabetes but are not suitable for type 1 diabetes
as the remaining islets are
already maximally stimulated.
Exanetide is a GLP-1 agonist which also slows gastric
emptying and suppresses appetite leading to weight loss.