Central Line
Episode Number: 126
Episode Title: GLP-1 Agonists
Recorded: March 2024
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VOICE OVER:
Welcome to ASA’s Central
Line, the official podcast series of the American Society of Anesthesiologists,
edited by Dr. Adam Striker.
DR. ADAM STRIKER:
Welcome to Central Line. I'm your editor and host, Dr. Adam Striker, back
again today with Dr. Vaibhav Bora, member of the ACE editorial board. Dr. Bora
is joining us for a dive into the timely topic of GLP-1 agonists, a topic that
appears in the 21A issue of ACE, out now. This is one of those topics everyone
is talking about. Many of our listeners are, I'm sure, very familiar with at
this point. So I'm looking forward to this conversation and hopefully we can
shed a little more light on this class of drugs and also hopefully provide a
little bit of, uh, current information to our listeners. So, uh, Dr. Bora,
thanks for joining us today.
DR. BORA:
Thank you, Dr. Striker, for having me on. It's a pleasure to be here.
DR. STRIKER:
Well, great. Before we get into the topic, as we often do on Central Line,
do you mind just telling us a little bit about yourself? So our listeners get
to know, you know, a little bit about your background and how you got involved
with the ACE program.
DR. BORA:
Absolutely. So, um, I'm an associate professor and director of critical
Care division with the department of anesthesiology and perioperative medicine
at Medical College of Georgia in Augusta. My expertise lies in, uh, critical
care and cardiac anesthesia, and I'm board certified in both these specialties.
In my role as an academic physician I'm involved in educating residents,
critical care fellows, and medical students. Throughout my career, uh, when I
was a resident and a learner, I was, uh, relying on ACE program to expand my
knowledge and to prepare for the exams. And as an attending, I used it for CME
credits, and I found it to be an invaluable resource. And joining ACE editorial
board was my way of giving it back to our specialty and contributing to the
education of our current and future physicians. And being a part of this
committee allows me to continue my own learning journey, while helping to shape
a valuable resource for anesthesia professionals worldwide.
DR. STRIKER:
Excellent. Well, on Central Line, as some of our listeners know we often
tackle a specific topic from the current issue of ACE. And this one, I think is
pertinent because of how much lay press this class of drugs has gotten
recently. But importantly, it has effects on our patients when they present for
anesthesia. So I think it's a very timely topic for for a couple reasons. I think
unless any of our listeners have been hiding in a cave for the past year or so,
I suspect most of our listeners will have heard about the success of these
medications, the GLP one agonists. But just in case, the drugs we’re referring
to are drugs like ozempic and agave, why don't we start with how efficacious
these drugs are? How do they work? What is the mechanism of action and why are
they so effective?
DR. BORA:
So the GLP class of drugs like Ozempic and Wegovy are but what we call
them by the trade name, they exert their effect by lowering the glucose as we
know that the glucose control in body is managed by an integrated hormonal
system. These medications, they are a class of medications or beta one like
peptides, these are also the human incretin hormone which are involved in
linking the nutrient, which are absorbed from the gastrointestinal tract with
the release of another increting hormone called GIP. And these hormones link
the absorption of nutrients with the secretion of insulin from the pancreatic
cells. The GLP one, in particular, enhances the glucose dependent insulin
secretion, meaning it stimulates the pancreas to release insulin in response to
the rising blood sugar levels. Additionally, they have several additional
effects, like delaying the gastric emptying. So GLP class of drugs slow the
rate at which food moves through the stomach into the small intestine. This
delay helps to regulate the release of nutrients into the bloodstream and
preventing rapid spikes of blood sugar level after the meals. This class of
drug also reduces the glucagon, which is another hormone which is produced by
the pancreatic alpha cell that acts to increase the blood sugar level. So GLP
receptor agonists help to reduce the release of glucagon, thereby lowering
blood sugar levels after the meal. They also have a central effect -- they
decrease the appetite and the food intake, which can lead to weight loss in
certain individuals, and thus these medications are also used for management of
obesity or weight management.
So these GLP class of drugs they can be in three categories. These are
GLP one receptor agonist, the dual acting GLP one and GIP, which is glucose
dependent insulinotropic polypeptide agonist, or the DPP four inhibitors which
is dipeptidyl peptidase inhibitors. So these are the three classes of drugs
which fall in this category.
Now, they are particularly appropriate in diabetes management alongside
other diabetic medications like metformin. They are specifically useful, and
they have proven their efficacy in the current literature at least about
efficacy and prevention of atherosclerotic cardiovascular disease in these
diabetic patients. And diabetes, as we know, is a very prevalent disease in the
United States. They also decrease the glycated hemoglobin. And like we
discussed, they are also used for weight loss. The good thing about them is
they, um, do not cause hypoglycemia until they are also combined with another
hypoglycemic drugs for diabetes management. So this is what it makes them a
very attractive drug for people who are diabetics, specifically type two
diabetics, uh, obese people and people who have a combination of type two
diabetes, obesity and, um, atherosclerotic cardiovascular disease.
DR. STRIKER:
What about Tirzepatide? That works a little bit differently. Do you mind
talking a little bit about that one specifically?
DR. BORA:
Certainly. So Tirzepatide is a novel medication, which somewhat differs
from the other GLP one agonists because it's a combined GLP one and GIP
agonist. So that gives it a little bit of a different mechanism. Like other GLP
one, the receptor stimulates GLP one receptors, leading to increase in insulin
secretion, decrease in glucagon secretion, and slowing the gastric emptying and
a feeling of satiety. However, it also targets the glucose dependent
insulinotropic polypeptide, the GIP receptor, resulting in an additional
glucose lowering effect, so it acts via two mechanisms. The dual receptor
agonism kind of increases the efficacy of this medicine as compared to the
traditional GLP one receptor agonists. In clinical trials, Tirzepatide has
produced superior reduction in hemoglobin A1, C levels and body weight
reduction compared with other GLP and a certain other antidiabetic medicines. Typically
administered subcutaneously. And what makes it, uh, somewhat attractive is it
is once a weekly dosing, similar to other long acting GLP one agonists.
However, its potency may allow for a lower dose as compared to the traditional
GLP one receptor agonists, while achieving a similar or a superior glycemic and
weight loss outcomes. Overall, it has demonstrated a favorable safety profiles
and a side effect similar to those observed with other GLP one receptor
agonists, like the GI symptoms and transient increase in heart rate and a rare
cases of pancreatitis. However, in the initial trials, it has been a pretty
safe and much more effective as compared to the other similar medications.
DR. STRIKER:
What brand name should we be looking for? You mentioned several
subclasses of these medications. As anesthesiologists, which ones should we
keep an eye out for?
DR. BORA:
So one of the things which we kind of as a perioperative physician deal
with is that these newer classes of medications and we need to know their brand
names as well, because sometimes our patients or the other providers may refer
to them by the brand names. So a GLP one receptor agonist, these are relatively
newer class of drugs. First one was Exenatide which was approved in 2005. It
comes with a brand name bydurian. It's a subcutaneous injection which is given
twice daily. Then the second one is liraglutide. It was once out in 2010, comes
with a brand name victoza. It's administered as once daily subcutaneous
injection. Then we have elbeutide. It was introduced in 2014 with a brand name tanzeem.
It's given once a weekly subcutaneous injection. We have a gelectrutide with a
brand name Trulicity. It is administered as once weekly subcutaneous injection.
We have Lixisenatide, which was introduced in 2016 with a brand name Nexium
adlikim and it's given as once a daily subcutaneous injection. Semaglutide was
introduced in 2017 with a brand name Ozempic for diabetes and wegovy or
obesity. It is administered as once a weekly subcutaneous injection for
diabetes and once a weekly subcutaneous injection or oral tablet for obesity.
The newest one is to terazapetide with a brand name zero for diabetes and …. for
obesity. It's given as once a weekly subcutaneous injection for diabetes and
once a weekly subcutaneous injection for obesity.
Now, these brand names may vary depending on the region and the country,
and it's important to be familiar with the different brand names for accurate
prescribing and for anesthesiologists as a perioperative physician, to know
what was the drug, what was the doses, and when was the last time the patients
may have been taking these medications?
DR. STRIKER:
Well, that's a specific area I do want to talk about. Before we get to
that, though, let's talk a little bit about how these agents interact with
insulin. Is there anything that we need to know specifically about that
interaction?
DR. BORA:
So the GLP receptor agonists, they interact with insulin and play a
crucial role in glucose homeostasis. Like we talked about these being the
ingredient hormones which are secreted from the intestinal cells. So they
stimulate the insulin secretion from pancreatic beta cells. So GLP receptor
agonist stimulates the insulin secretion from the pancreatic cell in a glucose
dependent manner. They enhance the insulin release when blood glucose levels
are elevated. But the effect diminishes as the glucose levels normalize,
helping to prevent hypoglycemia.
They inhibit the glucagon secretion as well. So they suppress the release
of glucagon, which is a hormone that raises the blood glucose level by
promoting glycogen breakdown and gluconeogenesis in the liver. By inhibiting
the glucagon secretion, these reduce in the hepatic glucose production, and
they maintain glucose level within a normal range. This, uh, GLP receptor
agonist, they also promotes satiety and they improve the beta cell function.
Uh, some literature about long term treatment with GLP agonists have been
associated with improved beta cell function and preservation of pancreatic beta
cell mass. They also complement the action of insulin. So when used alone or in
combination with other diabetic medications like insulin, they lower the
insulin requirement and they reduce the weight gain, which is associated with
the insulin therapy. And they improve the glycemic control at the same time
without increasing the risk of hypoglycemia. So overall, they play a
multifaceted role in regulating glucose metabolism by enhancing insulin
secretion, inhibiting glucagon release, slowing gastric emptying, promoting
satiety, and improving the beta cell functions.
DR. STRIKER:
Let's talk about side effects. We know there are some. What should we be
on the lookout for and what patient populations might be more apt to see those
side effects.
DR. BORA:
Now, when we are talking about these medicines, it's also to acknowledge
that they can be really beneficial. And many patients in terms of glucose
control and weight loss. However, like with any other medication, there are
some things which we need to keep an eye on.
First of all, the gastrointestinal side effects are quite common with GLP
one receptor agonists. We are talking about things like nausea, vomiting,
abdominal discomfort. Now there is some literature that these effects they do
ease up and the patients develop innovative tachyphylaxis to these side effects
over duration of time. However, these can be very bothersome in some patients,
especially when they are starting out on these medications. Then there is an
issue with hypoglycemia. We know that GLP one receptor agonists tend not to
lower the glucose blood sugar, but when combined with other diabetes medicines
like sulfonylureas or insulin, they can add up to the risk of developing
hypoglycemia. Some patients can have an injection site reactions which may range
from redness, swelling, itching to anaphylaxis kind of reaction. And then
there's a risk of inhibitions, whether it's pancreatitis or precipitating a
episode of hemorrhagic or non hemorrhagic pancreatitis. It's also people who
are allergic to them. They can develop severe allergic reactions. And one thing
that you need to keep an eye on. There's also some literature about, um, more
serious side effects, uh, like C cell tumors. Now, these are rare, but they are
important to be aware of. And patients should be informed about the signs and
symptoms of serious diseases like pancreatitis and thyroid cancers when they
are being initiated on these drugs. Finally, we need to be cautious with these
agents in patients who are having kidney problems to start with, and that dose
adjustments may be needed to avoid more side effects from these drugs in these
patient populations.
DR. STRIKER:
Are there specific patient populations? Patients with diabetes that are
on these medications versus patients that are on them for non-diabetic reasons.
Do we have a different set of concerns when it comes to perioperative care of
these patients? Or is it the same list of things we should be concerned with
and the same guidelines we should be following when it comes to the withholding
of these medications?
DR. BORA:
So in terms of the perioperative management, in June, the ASA task force
on perioperative fasting put out a consensus based guidance for perioperative
physicians and providers for management of these patients who are taking the
GLP one receptor agonist drugs. So according to the ASA guidelines, if it's an
urgent or emergent case, and we find out that these patients are taking the
medications, then we still will proceed because it's an urgent and emergent
case with a full stomach. Precautions I will consider rapid sequence induction
or like putting an end tube before intubation or in cases where awake
intubation is a possibility to avoid any risk of aspiration. When it comes to
elective procedures, the recommendations are pretty clear. In terms of the
patients taking, the GLP agonist should consider discontinuing them on the day
of surgery if they are taking it on a daily dosing basis, and a week before if
the patients are taking those ones which are dosed on a weekly basis. Regardless
of whether the patient is taking a GLP one agonist for type two diabetes or
weight loss, and regardless of the procedures they are undergoing, these
guidelines stay the same.
Now, discontinuation may sometimes lead to hypoglycemia during
perioperative period. So when discontinuing these drugs, an endocrinologist
should be involved in the decision making to bridge the gap on the day of the
procedure itself. If the patients are taking the GLP receptor agonist, it's
recommended in order to avoid the risk of pulmonary aspiration of gastric
content, that we take a thorough history and physical examination and looking
for the signs of severe nausea, vomiting, abdominal pain, and considering a
gastric ultrasound. When patients have discontinued that thing. In fact, from a
personal experience, I would say we had this patient there which was on these GLP
agents, and they had some nausea and vomiting, and doing a stomach ultrasound
led us to kind of cancel the case on the day of surgery because even though
they followed the same NPO guidelines, there was a significant amount of
gastric residual material because of the delayed gastric emptying from these
agents. So since it was an elective case, we ended up rescheduling the case and
holding it for a little bit.
DR. STRIKER:
We'll just follow up on that specific case, just out of curiosity. I
assume they continue to withhold the medication for the rescheduling. Is that
right? The one you're talking about? Were they rescanned then with another
ultrasound when they presented again?
DR. BORA:
Definitely. So at our institution, um, we kind of have made it a pre-op
habit where if they are bad with these agents, we have a set of providers who
are comfortable doing the gastric ultrasound, and we are training our entire
department to do that, where we would do a gastric scan before these patients,
they are going for an elective procedure. Now for an emergent procedure, we
have to kind of just proceed with the case with the full stomach precautions.
But for elective cases, that is what we are trying to use based on the ASA
recommendations. For this particular case, we were fortunate enough that the
surgeon had a scheduled available next week, and we were able to squeeze them
in and we left them off of their medications for the duration and called an
endocrinology consult, uh, to bridge the gap with some sliding scale and some.
DR. STRIKER:
Well, this leads into the question I was going to ask, which is, from
what I understand, there are a lot of logistical hurdles here when it comes to
scheduling these patients for surgery and having especially on the ones that
have the non-daily dosing of these medications and canceling cases,
rescheduling. I work in the pediatric population where we're starting to see
some of this, but it's obviously more prevalent in the adult population. And I
wanted to get your take on the logistical concerns, because when I was just at
a meeting recently, this was a topic of discussion. And there seems to be
concern from the anesthesiologists on the current ASA guidelines. And is the
two conservative? Is it adequate? And so I guess I'm asking a two part
question. A what's your take on the overall anesthesia community and the
logistical hurdles involved? And B is this the most current, up to date
information regarding the medication and the discontinuation intervals?
DR. BORA:
Yeah. So this was one of the official guidelines from ASA. So for now we
have to follow them. But these are the new class of drugs. And it's a newer
thing which is introduced. And the specific risk of aspiration. We know that
it's a very bothersome and it can cause significant morbidity and mortality. So
as a perioperative physician, you know, our foremost goal is to do the safest
things for our patients. And so we have developed a system in our pre-op clinic
here that the patients get tagged when they are taking these medicines, and the
first time when they are seen either by the surgeon's office or by the pre-op
clinic, and they are communicates a lot between the surgical scheduling and the
anesthesia scheduling. So we can hold these medicines. If it's a long duration,
we will have the endocrinology involved to bridge them. But if it's something
which can be scheduled based on the surgical scheduling and timing from when
the patients are taking it, we proceed with the procedure. So far, we have had
our logistical glitches. So that's why as a second layer of safety defense,
what we have tried to do is train most of our anesthesiologists in the point of
care gastric ultrasound. And at least we have developed a core team of
physicians who can do the gastric ultrasound. It's pretty easy to perform, and
we have had a recent success in terms of we haven't had any, uh, so far, knock
on wood, um, aspiration events with these particular cases, uh, and we were
able to avert some of them by using the point of care ultrasound. So with the
guidelines we have in our hands right now, the ASC guidance and it will get
updated. And like we discussed before that some patients do develop
tachyphylaxis to the gastric emptying and the decrease in gastric motility. But
having a gastric ultrasound immediately before the procedure always gives us
that another layer of safety, uh, as these people may still have fuller stomach
even though they have followed the prior guidelines or guidelines on a patients
who are NPO guidelines on patients who are not on these agents.
DR. STRIKER:
In your experience using gastric ultrasound, do you feel like maybe the
guidelines are not conservative enough? Are you seeing a lot of patients that
are coming through with residual volume in the stomachs under ultrasound?
DR. BORA:
Yeah. So like most of these people are also having diabetes, which is
another risk factor for gastroparesis. And they may be obese, which may be
another factor which we need to consider in terms of intubation. So it becomes
a decision which has we have to integrate a lot of factors in terms of the
logistics of the things, in terms of the patient's safety. And the foremost
thing becomes the patient's safety. So if we look out for it, I believe at this
point the best option we have is to look at the ultrasound and see if the
stomach looks like it's there's some material in there. Then we still will
proceed with the rapid sequence induction and the aspiration precautions. It at
least gives us a pretest probability, if I may say that. Is it safe to proceed
or not. And that can be very helpful in a multidisciplinary decision making,
whether to proceed with the case or not.
DR. STRIKER:
Right. In your experience with seeing these patients and then doing the
gastric ultrasound, are you seeing a lot of them with residual volume where you
feel like maybe you should be pushing out the discontinuation of the medication
even further?
DR. BORA:
Yeah. So my experience personally has been a mixed one because it also
depends. If the patients were on these medications for long time, then I have
not seen a whole lot of especially they followed the advice given by the
preoperative clinic and they were able to stop it. And we did not see a whole
lot of gastric volume. And in 1 or 2 patients, I have seen that the even after
stopping it on that time, they still had the gastric volume. So it's very
dependent on the patient. And we have to tailor the management on every
particular patient because their response may be different. And there's
definitely a lack of randomized trials yet to see, like what would be a perfect
guideline. And um, we all know the medicine. There is nothing which follows the
textbook. So, uh, safety always comes first. So probably like I would still
continue to do a gastric ultrasound in these patients were on these medicines
or at risk of aspiration to give myself another layer of confidence and comfort
taking care of these patients.
DR. STRIKER:
Well, let's, uh, change the direction just a little bit. We know these
drugs have off label use. What is the potential for abuse of these medications,
and is there anything specific to that aspect of the utilization of these
medications that we as perioperative physicians need to be aware?
DR. BORA:
So we know the phenomena of drug misuse and abuse for weight loss
purposes have frequently been reported in the literature. There's a thing
called the image and performance enhancing drugs. So these are a wide range of
drugs across various pharmacological categories, which are misused to obtain an
alteration or enhancement of the physical performance or appearance as it
occurs with the slimming products. Glp one agents they do have a potential to
be abused or sometimes used off label for these indications. And now that we
are in a world of social media, there is a potential that people who are image
conscious or performers, they may use it and these are non-medically prescribed
drugs. So that's one thing which we have to kind of keep an eye on when we go through
our substance abuse history during a preoperative evaluation. This is one of
the things which we may have to consider. Some subset of patient populations in
terms of monitoring and education. It's also crucial for us to kind of keep a
close eye on the prescribed ones. And the physicians who are prescribing it may
sometimes give us a head up if the patient is using more of these medicines, if
there's a regulatory issue around the prescription refills, etc..
DR. STRIKER:
Well, before I let you go, let's just talk a little bit about how this
topic was chosen for ACE. I mean, I know the timeliness and it makes perfect
sense, but the mechanism of choosing a topic such as this and just reviewing
how the decisions are made in general, what to include in the ACE program.
DR. BORA:
ACE stands out as an invaluable resource over years for anesthesia
professionals. The questions and each edition of ACE is spearheaded by a
dedicated 12 member editorial board, comprised of clinical anesthesiologists
from diverse backgrounds and diverse practice profiles. To ensure that the
content remains clinically relevant, accurate, and clear, we have quarterly
meetings at the ASA headquarters, where we meticulously select the content,
review it before the meeting, and then we review it all the content of during
the meeting to refine the content, and are aiming to deliver the highest
quality educational material. From its inception, since 2004, where it's
current available version in 2024, almost 20 years of its program, ace has
proudly evolved into one of the solid foundation material for many practicing
anesthesiologists around the world. As a part of editorial board, we are
committed to enhancing its value by incorporating sophisticated clinical
scenarios, content which is aligned with the currently published guideline to
say so, like the walking content which anesthesiologists should know, taking
care of these people, uh, day in and day out. Uh, with the upcoming release of
issue 21A, anesthesia professional will have an opportunity to deepen their
knowledge and earn a valuable CME credits with release two editions every year
one in April, one in October with 30 CME credits each, and talking about the
process of selecting the items for ACE, it's a meticulous endeavor. Uh, it
prioritizes the relevance, accuracy, and educational value. We carefully choose
the topics that align with the anesthesia practice, drawing from a reputable
sources, well published books, crafting questions that reflect real world
clinical scenarios. We as a editorial board work on clarity, precision and, uh,
user engagement is a very important part of our process. We get a feedback from
our subscribers, and based on that, we modify the content as needed for our
future issues. And summary. Uh ACE is dedicated to delivering a high quality
educational content tailored to the needs of our anesthesia community and
practicing anesthesiologists. Uh, and as a member of the editorial board, I'm
proud to contribute to this mission and help anesthesia professionals to stay
forefront in terms of knowledge in their field.
DR. STRIKER:
Excellent. Well, Dr. Bora, thanks for joining us today to not only
discuss specific topic, but also give us some more insight into the ACE
program.
DR. BORA:
Thank you. It was an honor to be here.
DR. STRIKER:
Absolutely. And for our listeners who are interested in checking out more
of the ACE program, go to the website asahq.org/ace. If you like the podcast,
feel like you're learning something from it. Tell a friend about it. Drop a
review on your favorite podcast platform. And tune in again next time. Take
care.
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