Well, howdy y'all.
Welcome back to another episode of You're A Mom on Drugs.
Uh, my name is Josh Klaus.
And I'm Jennifer Seltzer.
The aforementioned mom on drugs, but not that she's doing them, but she is talking
about them because my dear mother is a doctor of pharmacy from the University of
Texas at Austin, Hook and Horne's.
And, uh, I am just a lowly bachelor of science, you know, and also have, I do
have my master's in public health, but I do not have the knowledge of the
pharmaceutical world like my mother does.
Um, we decided today, um, that today will be a fun day to delve into the realm of,
uh, semi-glutites, um, or semaglutides, semaglutides.
Yeah.
Or it's actually GLP-1 receptor agonists.
That's true.
Um, if you haven't known anything about these, these are the common names
are like Ozimbic and Wegovi.
You've probably seen them in the news as being weight loss drugs.
And we thought that these were interesting molecules because obviously
people being overweight and obese in this country is quite prevalent.
Um, and so I think these drugs are obviously getting a lot of attention.
Um, and I think a lot of people are, including myself, are very confused
of their mechanism of action.
So I decided to ask the mom on drugs to walk us through, um, these GLP-1 agonists.
Um, so Dr.
Seltzer, AKA mom, uh, you want to give us a introduction of what these drugs
are and what they are used for and let us know what, what, what's going on here.
Well, whenever I start a, when I was in drug information, it was always, you
kind of give a little bit of background about the disease state first before
you really kind of dove into the medication that was being, um, addressed.
And so first of all, I want to talk about the fact that sometimes medications
are approved for one particular use by the food and drug administration, but
a new indication or a new use might be discovered, um, in addition to whatever
it was FDA approved for.
And so that's what has happened with as initially with Ozempic and it was due to
some of its mechanisms, which we'll get into, um, in a little bit.
So, uh, Ozempic, although it is, it's actually FDA approved for managing
type two diabetes mellitus.
Um, it also then became, um, noted as a significant, um, uh, effective
medication for, for weight loss in patients with obesity.
Yeah, I think they noticed that in those patient populations that there was
significant weight loss.
Yes.
And there's some reasons for that.
We'll get into in just a little bit.
Um, and again, it's caused, um, some media coverage.
We've, I think that there have been celebrities using it for weight loss.
I believe I read some in like a, you know, throwaway journal that it was,
there was some, uh, whoever was it, Jimmy Fallon that hosted the Academy
awards or whatever, made some comment about everybody looking good.
Cause they were on there as Zempic or something.
So, yeah.
So, um, so people with obesity might require other methods to help with
their weight loss in addition to diet and exercise changes and stuff.
So we'll get into that a little bit more.
Um, there was, there was a poll done by Gallup in March of 2024 of the, well,
this year, it showed that 6% of all us adults that was about 15.5 million
adults in the U S have used or are using an injectable anti-diabetes medication.
And 3% of them stated they were specifically using it for weight loss.
So, um, and those, those, those agents that are used for weight loss are
primarily Ozempic, Wigovia and sexinda.
So in the last three months of 2022, there were over 9 million prescriptions
for Ozempic and Wigovia and they were primarily written for weight loss.
And that was a prescription volume increase of 300% from the end of
2020 to the end of 2022.
Um, and it had, it has caused some medication shortages in these medications.
So, um, you know, for using Ozempic for a non FDA approved medication versus
somebody actually needing it to manage type two diabetes, um, you know, it can
be kind of, you know, tricky and stuff as far as they're both conditions that
are, you know, that can need medication help, but, um, so actually, as I read,
there is actually a free tracker that people can utilize to find out whether or
not these agents are available in their area.
This is what I thought.
That was really useful.
So that's really cool.
Also, interestingly too, and this, this is probably a no brainer, people with
private insurance or generous health plans or people with wealth are more
likely to receive GLP one receptor agonist for weight loss than anybody
with a medicator Medicare plan because they're not covered by Medicare Medicare.
Yeah.
I, I just, I have an anecdote because I was mentioning to somebody that
we were doing this episode and they mentioned, uh, they said, Oh, I've
actually used these GLP one agonist, uh, specifically some, uh, some agglutine.
Okay.
And I was like, Oh, how'd you get it?
Cause she wasn't obese.
I was like, how did you get it?
And she's like, Oh, well, I'm not sure.
Well, there is this compound pharmacy in Canada that essentially will make it.
And then they will distribute the vials.
And I mean, essentially it's drug dealing.
I mean, it's basically, it's just, it's just, you take this drug and then you
sell it, you know, whatever the market price is, because in the United States,
at least you can really only get it legally via prescription, which is only
available for people who have type two diabetes or have a BMI over 27.
Um, so she was telling me that she was doing this and, um, and you know, watching
people take it because she also said that there are a lot of these quote unquote
weight loss clinics that will offer and say that they're offering these, these
semakotides, but actually all they do is they get a vial, let's say from these
compound pharmacies, which are under the radar and they, they're not regulated
by the FDA, they're just kind of doing whatever they want to do.
It's the wild west out there.
And, um, and they'll just dilute the dose.
So technically they are giving you, um, you know, uh, Ozempic or
Wigovie, but actually they just water it down.
So it's basically just like, um, homeopathy or, uh, it's like this idea
of like this really dilute substance.
That's not really doing anything.
Maybe it has a placebo effect, but there's such a hunger for this and the,
the supply hasn't kept up with the demand from what I've heard.
It's technically demanding to make these molecules.
Um, so you just aren't able to make them as quickly as people want them.
So just want to talk a little bit more about those, um, compounding pharmacy,
um, manufacturing things in a little bit.
That sounds great.
Uh, but, but as far as, so the average wholesale cost of one milligram of Ozempic
and the dose of Ozempic that, um, people shoot for, I believe is three milligrams.
Um, a week and put a one milligram dose that it would be a one month supply.
So a one month supply of a one milligram dose is $1,162.
And that's the average wholesale cost.
Now that if you have insurance, then you don't pay that.
But if you had to pay out of pocket, that's pretty hefty price tag.
And Wigovie is higher than that.
It's a, it's over $1,600.
Yeah.
So you basically paying close to 12 to $14,000 higher than that, maybe like
$15,000 a week.
Yes, a year for this medication.
Yes.
So, so, so let's, so let's, let's dive a little bit into obesity.
Um, and because that's really the target of what these medications have been, um,
uh, used for, you know, as far as what we're talking about today.
So obesity is really a serious and it's a common and it's a costly chronic disease
in the United States and it's observed in one in five children and two in five adults.
Um, adults, um, that are primarily affected with obesity are going to be those that
may have less education.
And again, this is just the demographics of this disease.
They're non Hispanic black adults that are having more problem with this.
Also, um, they may have concurrent serious health conditions like heart disease or
diabetes, um, and they may have other diseases as well.
And children, it's one of the most, interestingly, it's one of the most common
chronic pediatric diseases.
And it's multifactorial, so it can be socio ecological.
So it's like the environment that they live in, um, what, um, you know, what's
what they're, uh, how much money their parents make, what, what are the, what
kind of foods they get as well as generic factors and stuff.
And it's again, more, more common in children who have been poverty or don't
have as many resources and stuff.
And so, so children especially will benefit from behavioral health
modifications, um, as far as, and lifestyle treatments for their eating
habits, that's going to help them because obesity has long lasting negative
health consequences.
And you would hopefully then carry this into their adult, um, uh, adult life
that they would continue to have those kinds of practices in place.
Um, the prevalence of obesity and what prevalence means is that it's the
proportion of a population with a specific characteristic over time.
With a specific characteristic over given time periods.
So that's what prevalence is.
And so the prevalence of obesity in the United States increased from 30.5% to
almost 42% over a 10 year time period from 1999 to 2020, um, and Texas has an
obesity prevalence of 20, of 35 to 40%.
So they're right there in that higher level.
Do love our brisket and beer in this state and tortillas.
Yes.
Um, prevalence really doesn't change so much based on age, except that the lowest,
you know, age population, like the two to five year olds, it's kind of stabilized,
but even five year olds and older can have increasing prevalence of obesity.
So that's interesting.
So the, the, the age cohort, like between two to five has risen to a certain
percentage, you know, like from, let's say from 1999 to 2000 to this date.
And it's kind of stayed there.
It's plateaued.
Interesting.
Yeah.
So it's, you know, I think we also should mention that when we mention a lot of
these, um, socioeconomic factors, that these are more correlations, not causal
factors, like just because you're poor, it doesn't mean that you're going to be obese.
Right.
We, it could be a healthy user bias.
Like, like my mom said, it's like, if you have more resources, then you might be
able to have more free time to be able to go exercise or shop for foods that might
satiate you more than eating some of the, the processed foods that tend to be
that tend to lead towards non, not being satiating and you just tend to eat more
of those.
Um, so a lot of these factors are kind of all bundled together.
Um, but we don't mean to hold.
They're never implied.
A lot of these factors are causally related.
That's a great point.
Yeah.
That's a great point.
Um, in 2019 dollars, the cost of obesity was almost $173 billion.
So yeah, I did some, I did some basic math cause I was like, well, what if we
gave some of these drugs cause they're around, let's say $1,200 a month.
If we gave them, let's just say that the government said, you know, this is a
huge problem.
It's costing us $173 billion a year.
Um, even at the current price of the drug, if we gave it to every obese person,
it would still be more to pay for the drug than the cost of obesity itself.
So, um, we're still waiting for the price of those drugs to go down, for it to be
cost-effective because I do think we'll get into this later about the mechanism
of action and what the drug actually does.
But if you're looking at it from a public health or a cost-effective standpoint,
if you're able to give people these drugs and say, Hey, we're going to give
you this drug, it's going to increase your, you know, your, your quality of life,
life expectancy.
It's something we don't appreciate in health.
It's not just about lowering mortality, also morbidity and this idea of like,
you want to be able to run and play with your grandkids.
Like you want to be able to walk up a flight of stairs without being winded.
And, um, and some of that doesn't get captured by dollars as well.
Um, but so sometimes, you know, making these calculations, like is the
juice worth the squeeze?
Um, and, but I'm hoping that over the next, and maybe my mom and I maybe might
debate the merit of giving a bunch of people pharmaceuticals, but I think
sometimes you have to debate, like giving people this drug and paying for it now,
which might be really expensive and people might be up in arms about, you
know, Medicare, Medicaid paying for these drugs, but it's like, we're paying for
it anyway in our healthcare system.
So we might as well prevent it before it gets further.
But that's just my point about like, it's just, it doesn't seem cost-effective
at the, at the moment.
Right.
Yeah.
So, but yeah, there's like, like you said, it's so complicated because there's
so many other factors, cause like, what if you were able to give them this drug
and then you reduce their diabetes complications or their heart disease
complications, then they extend their life and then they are more contributable
member of our society for longer and stuff.
Right.
What price tag do you put on that?
Able to be a grandparent and affect, you know, a child's life that, you know,
might make them a better citizen as well.
Right.
There's all these dynamics when people die and get sick, it has this
incredible ripple effect, um, that you're trying to always prevent.
Right.
So, so why does obesity occur?
Well, it's not just a behavioral problem.
Cause sometimes we want to look at people and say, oh, they just need to get off
their sofa, you know, but it's not, and in some patients it is like that, but it's
a really complex metabolic disease.
And so you, you actually, we're not going to go, I mean, Josh may go into the
actual details of all the pathways of the disease state, but, um, it's, it's
really, obesity is really a dysfunction of the normal pathways that regulate body
weight and, and specifically body fat.
And so, so what happens with obesity is so you, you end up with increased energy
storage resulting from an imbalance between energy intake and expenditure over
time.
So that makes sense.
It's like we take in more than we're burning out, burning up and stuff.
So, but it is multifactorial.
And so, um, and there can be other underlying health conditions and sometimes
medications and a small percentage of patients can help to contribute to
obesity as well, but that's not the main reasons for it.
And, um, and so a lot of, there are a lot of factors that can regulate
appert, appetite and energy balance because appetite interestingly is
affected by many neurotransmitters in the brain.
So, yeah, it's really well, I mean, just as, uh, my mom definitely hinted on it
of talking about a little bit of the pathophysiology of this condition.
I think it's so well said to call it a metabolic disease rather than a disease
of like weak will.
Um, um, it, it, you have to think about what humans were like prior to
civilization, like the idea that we, we were constantly either hunting or
gathering and food was very scarce.
Like the idea of like bacon is just it, then that concept does not exist in, in
ancient human, human existence.
So our, our system was basically, you know, cultivated to say, if we get
something that's really calorically dense, let's say like we find a beehive
with honey in it, we're never going to find that again in probably a couple of
months, because you know, there's a lot of competition out there with nature.
Um, and so your body is primed to store this because you know that there's going
to be a lot of scarce food out there in the real world.
So your body is really good about winning, getting a caloric excess.
As my mom alluded to the first law of thermodynamics, there's no
perpetual motion machine.
The energy you put in is going to be the energy that comes out and is either
going to come out as heat, which makes us, you know, uh, exothermic endothermic
organisms, or it's going to get stored in some way, either as glycogen or
fat or some other thing.
And, and he, and we, we have evolved essentially just to be these creatures
that are really good at storing stuff for the winter.
As anyone knows who lives in a modern society, we have food everywhere.
I mean, you can get, you, you could go into a gas station and get 2000
calories for maybe $10.
Like it is incredible.
The amount of progress that we've made on food abundance.
I mean, we've solved, especially in the West, we've followed starvation.
Um, but we now have, I think on average, the, uh, people in the West
consume 3,500 calories a day.
And if you think about that, like a bank account, if you do that every day,
that's going to add up over time.
And it makes, it makes a lot of sense that people would put on a
couple of pounds every year.
Yeah.
Cause you think of what would you have to do to burn off 3,500 calories a day?
That is correct.
And it's actually quite amazing because you can actually do that relatively
easily and we're going to get to that mechanism later.
Um, but you just have to think about it like accruing debt.
It's like you're, you're putting your body into debt and the debt is
collected as fat and, and it's marginal.
So most people they collect, you know, a pound or two a year, but if you do
that over 20 years, you're going to gain, you know, potentially 20 to 40 pounds.
Um, and that's how you get something like being overweight or obese.
So just, just to say that like our bodies were designed to basically
store this material and it was something that was really beneficial 200,000
years ago, um, when we were hunter gatherers, but now in modern society,
um, it is causing a lot of downstream consequences.
So, so, um, obviously, I mean, the clinical presentation of obesity is,
is it can be fairly obvious.
It's usually, you know, readily apparent in people, people, interestingly,
people usually don't seek help for obesity unless there's another obesity
associated health condition.
Um, and obesity can be measured by two, uh, uh, two techniques.
One is called, um, body mass index or your BMI.
And certainly people have heard of that.
And when you calculate your body mass index, it's your weight and kilograms
divided by your height in meters squared.
So it's excuse me.
It's kilograms per meter squared.
And you can do it in pounds per inches as well, too.
There's a different calculation for that as well, but there's different
interpretations for how you, you interpret your BMI for both adults and kids.
So for an adult to be overweight, as Josh alluded to earlier, your BMI is
going to be from 25 to 30 kilograms per meter squared, whereas obesity is over
30 kilograms per meter squared.
With kiddos, your obesity, um, target is going to be your, your BMI is going
to be greater than the 95, 95th percentile for your age and sex.
So if you are, if your BMI is greater than the 95th percentile, there was
this growth chart that you plot kids on.
Then can you explain to people maybe who not know what the 95th percentile would be?
So, yeah.
So when, so when you, when you, when you, when you, when you,
so there are these graphs for kiddos and it, I believe it's, they're, they're
male and feel, male and female, um, uh, uh, differences.
I mean, there's a, there's a graph for males and graph for females because
girls and boys grow differently.
And it's, it's plotted based on height and weight.
And so there is a, so when you, when you, and so there's going to be an average
weight and an average height for kiddos based from birth to 18 years of age.
And so then there's a graph that's created, um, with, and, and so when, if
you, the average is going to be 50% because you know, right in the middle
is going to be 50%, so they call that the 50th percentile and then they.
Gradated down and up.
So you've got 10 percentile 95th percentile and it's kind of these
lines that kind of parallel that 50th percentile they curve because it goes,
it kind of like, looks kind of like an S as kiddos get older and stuff, but it's
based on their age and their weight and their height and stuff, as far as how
that, how they're growing.
So you want to, you're, you're catching kids that either are going to have
issues with underweight or some growth issues or whatever, or the, or overweight
as well too, so the 95th percentile is going to be the, the top level in this
growth chart and stuff, so yeah, so that, so yeah, so, um, so does that, does that,
hopefully that makes sense to people and stuff.
Yeah.
It's like, I mean, I always say like, if you picture a room with a hundred people
and most of those people, let's just say it's height, for example, most of the
people are going to end up close to the middle, like let's say it's, you know,
let's say we have a hundred people, they're probably going to end up around
five, six, if they're adults and that's going to be the average, but then you're
going to have a couple of people who are like six, four, or a couple of people
like myself or, or five, four, or like you four 11, you know, so you're going
to be in the fifth percentile of height, which is basically, you know, basically
the bottom of, of, on the other side of the curve and then someone who's an NBA
basketball player is going to be in the 95th percentile, which is the top.
So these outliers, but as my mom mentioned over time, the prevalence has
changed, so these averages shift, you know, that's why like, um, so you can
have a BMI that's why it's these, these measures are sensitive to changing
averages, right?
Because like you can have someone who's like myself, like five foot four, 160
pounds, but if the mean or the average is that, then I'm not going to have a BMI
over extended, but if you're comparing it to like the 1930s BMI, then I'd probably
be overweight or obese, but you're always kind of comparing it to the population
today and that can be a bit problematic, right?
Because if you're trying to get to an ideal or what they should be, um, if the
average is always shifting and tending up, if we're kidding, continuing to
getting more obese or more overweight, then that average is shifting up.
So you want to kind of get back to one that is somewhat healthy, right?
And, uh, um, and that's going to lead to our next metric as well, which I think
is, I think is a better way to measure.
It's a better, so the other metric is, is waist circumference and waist
circumference is measured.
If you think about, if you can feel your waist and you can feel kind of the top of
your hip bones, then that's kind of where you want to measure, you want to take a,
uh, a measuring tape and put it around that particular area.
And so a high risk waist circumference for men is greater than 40 inches and one
for women is greater than 35.
So you, obviously you want your waist circumference to be smaller, but your
waist circumference, um, should be measured in concert with your BMI.
If your BMI is between 25 and 34.9 kilograms per meter squared above that, it
doesn't really give you a whole lot of extra information, but below in that
range, it can help, it can help assess additional metabolic risk cause it could
be that somebody doesn't look really obese or overweight, but they're carrying
around extra weight that could then contribute to some potential other health
issues that you're trying to identify.
Yeah, that's a good point.
Like for example, I'm always going to refer to myself, but I'm a very stocky
muscular guy and so like most of my weight is primarily a muscle, so I might
have a high BMI, but it doesn't really tell me a lot about the fat content
inside of my body and yeah, supposedly there could be a really skinny person
who like I do have a friend who just drinks and eats a lot of alcohol more
than me and he's really, he's always skinnier than me, but I'll bet if I
looked at his liver, it would not be as healthy as mine.
So sometimes these are just rough metrics to help get people into to see
a physician or a medical professional so that more steps are like, Hey, should
we actually take a look?
But I just want to let all my skinny folks out there just because you're
skinny doesn't mean that you're healthy.
This is a metabolic disease, which most of the time happens on the inside.
But sometimes the outside does give you an idea of what's actually
going on on the inside.
So, so we all know this, the general management strategies for weight
loss are going to be managing your diet and eating healthy as well as getting
exercise and then also some people do need behavior modification because
people, and we all know we all either have experiences personally or know
someone where we use food as a compensatory mechanism for our emotions.
And so that then can contribute to, you know, gaining weight and stuff.
So you just want to be careful of that as well.
So you can get help with that as well.
So you learn to not just be able to say no to food and maybe yes to a walk
when you're feeling kind of down and stuff.
So, so now we're going to turn the corner and we're going to start talking about
these medications that have been discovered to be used for weight loss.
And they are called GLP-1 receptor agonists, and it stands for
glucagon-like peptide-1 receptor agonists.
What they do is that they mimic something that's called an incretin.
This is something that we have in our body and it's a hormone.
And it's actually a group of hormones that are released in our gut after we eat.
And they're going to stimulate our pancreas to release insulin in response
to the food that we take in.
And the insulin is released from the beta cells in the pancreas and it's going to
help manage our glucose intake.
So it helps to lower our blood glucose levels.
These, these GLP-1 receptor agonists also help to stimulate our pancreas
slow gastric emptying and they reduce food intake.
Interestingly, there are also these GLP-1 receptors in several areas of the brain
that regulate the appetite.
So it's going to lower our weight, it's going to lower our weight with greater
fat mass loss rather than lean mass loss.
And it helps to fight against this weight loss plateau.
Joshua kind of alluded to this earlier.
So our bodies want to fight against continued weight loss.
And it's very, very normal for our bodies to do that because our body wants to
determine what a good weight is for us.
And it's even if our BMI says otherwise, because they want to, it's a defense
mechanism of our body to stave off starvation.
Yeah.
And also to maintain homeostasis.
We just like to be in balance.
And so if you're at a certain weight and you've been there for a long time, your
body's pretty good at maintaining that balance.
Yes.
So, so this, for this weight, weight loss plateau, your body is going to send
hunger hormones.
So that's going to, that's going to help you reduce the fullness hormones and
decrease metabolism.
So it will keep your weight stable so that you're kind of going to keep the
blood glucose higher rather than lower and stuff.
But GLP-1 receptor agonists can, can also change your body functioning to help
maintain and improve weight loss.
They don't just make you want to eat less.
So there's some physiologic things that are going on behind it as well too.
Yeah.
I mean, this is a cool molecule because as my mom alluded to, it says
glucagon like peptide.
And the reason they call it that is because there is an actual molecule called
glucagon in your body that is released and actually does get released by your
gut to promote insulin secretion in your body, but it's very short lived.
And, am I saying that right?
I, I'm not sure you're saying that right.
So glucagon is released to stimulate glucose, increase glucose levels and
stuff, whereas insulin is released to stimulate, it helps to, it helps to
lower your blood glucose and stuff.
So glucagon helps to increase your blood glucose and insulin is released to help
lower your blood glucose.
Okay.
So I guess it's, so it's just really, it's, it's attaching to the receptor.
Right.
Okay.
I see what you're saying.
So it's competing against glucagon to get on the receptor.
Right.
Okay.
So there are these natural ones in your body that are like GLPs, right?
Right.
Okay.
Right.
Um, and from the way that I understand it is that they're very short lived
because there's an enzyme, I think it's called DD4 that breaks it down
really, really readily.
Um, and so it has this very short half-life in the body.
Um, so what the novo Nordis did, what they did, the people who developed this drug,
um, first, I think lyraglutide before semaglutide, um, is that they added,
um, to basically two modifications to the molecule.
One was that they made it so it would dissolve into something called albumin.
Um, which essentially is really good for maintaining its circulation in the
blood flow and also to deny getting excreted out by your kidneys.
Cause you, you think about it, it's in your blood, your kidney is always
filtering things out of your blood to get it out, but if it's dissolved in
albumin, it has a much longer half-life in your body and also they had an
addition so it wouldn't get degraded by this enzyme.
So it allows it to have basically have a half-life or a shelf life in your body
of seven days, um, which is why we're going to get to this, the, how often
you dose yourself with some aglutide, you can basically take an injection once
a week, which is what correlates to being seven days in your body.
I just thought that was so cool that they designed it to be that way.
Just these two little fixes.
Um, and so that, that it would survive, um, obviously with the goal of, of
releasing more insulin, but then we have all these other side effects as well
that we didn't know what we're going to happen when we gave it to people.
So a really cool molecule.
It is really cool.
So, so there are actually several GLP-1 receptor agonists available.
Um, they are, they were initially primarily FDA approved or most of them
are primarily FDA approved to manage type two diabetes.
Um, some of the names you've heard are ozempic or trolicity.
That's dilaglutide or biota is exenitide.
Um, also, um, uh, liraglutide is Victoza.
So they've all started out by being agents that were used to treat type two
by diabetes, but liraglutide and semaglutide are the only two GLP-1 receptor
agonists that are approved for weight loss management.
So note that I didn't say ozempic because they created with govee for
weight loss management, but ozempic is actually not FDA approved for
weight loss management, but it's the same medication, the same generic
drug, semaglutide, they just have a different trade name.
I think they have to do that.
Cause I think wasn't the same with, uh, Viagra, right?
Like it was, it was, it was originally designed to be an angina, uh,
yeah, pulmonary hypertension or something.
Yeah.
So they discovered this side effect that men tend to like, and then they had to
basically go through the same FDA process, but you have to call it by a
different brand name, uh, because it has a different, uh, you have a different
health outcome that you're searching for.
Right.
No, that's why you can't.
Well, anyway, um, so, um, so, um, so one of the ways that you can
determine whether obesity treatment is successful is, um, the surrogate
marker of weight loss.
And so what, what, what I'm seeing by that is that we're looking for at least a 10% loss,
uh, 10% or greater body weight loss to determine that a drug that's for obesity
treatment is being successful to help with obesity associated complications.
Often patients that are, are seeking out a medication to help with weight loss, have
to show their public or private payer that they've tried other methods like
lifestyle management changes, including weight law, I mean, uh, um, uh, food, um,
diet, exercise, and maybe to show them their gym membership and be like, I've
been trying the fridge full of lettuce.
Yeah, really?
Yeah.
Whatever and stuff.
So, but, um, so, so, so, so, so, so, so, so, so, so, so, so, so, so, so, so, so, so,
so, so now, so, but so our GLP one receptor agonist, um, the, so I, I think
this is important for people to know.
So Saxenda, which is liraglutide is FDA approved as an, listen to this.
It's an adjunct to a reduced calorie diet, as well as an increased physical activity.
It's an adjunct.
So that means you're using it together with those for chronic weight management
and people with a BMI of 30 kilograms per meter squared or greater, or they have
one that's greater than 27, but they have some other weight related comorbid
conditions, such as heart disease or diabetes is also indicated for pediatric
patients, 12 years old and older with a weight above 60 kilograms and an initial
BMI that corresponds to 30 milligrams per meter squared or greater for adults.
So, um, so it is indicated for both kids and adults.
Um, Ozempic is only indicated for, um, maintaining blood glucose control in
addition to diet and exercise.
So it does not have a weight loss indication.
It's also indicated for reducing risk of major cardiovascular events.
And we're going to talk a little about that in just a minute too.
Um, and it, it's also that, and specifically it's major cardiovascular
events in patients with type two diabetes and established cardiovascular disease.
And with GOVI, which is the same generic drug as Ozempic is indicated for a
reduction in risk of major cardiovascular events in people with established
cardiovascular disease and either obese or overweight in combination with
exercise and, and, and, uh, diet improvements, or it is also indicated for
just weight loss for people who are adults and in patients, 12 years old and older.
Um, so it has both of those indications.
So, so again, we go V is for the cardiovascular improvement and for weight
loss, whereas Ozempic is primarily for type two diabetes and for
cardiovascular events.
Um, so, uh, Joshua alluded to this earlier for sex endo or liraglutide.
It's dose.
It was the initial medication, the, the GLP one receptor agonist that
was approved for weight loss.
It is actually dosed daily and it's a subcutaneous injection once daily.
And you, for these medications, you have to titrate the dose upward and titrate
means you start with a smaller dose initially, and then you go to a different,
uh, an increased dose every week because we're going to get to the side effects
of these drugs and that's primarily why we do that and stuff.
So, so again, this is going to take, it takes about six weeks to get to the
target dose with liraglutide or sex endo.
And if you have some adverse effects, you may have to slow the titration
upward to get what you, what you, to get to your, your targets.
Yeah.
The example that pops into my head is, um, I love coffee now, but I did not like it
when I was 15 and I remember the first time I tried it at my grandmother's house.
I was so disgusted by it that I poured basically like a half a bottle of
chocolate syrup in it, put some whipped cream on it.
I basically invented a Frappuccino and I was like, oh, I like this now.
So the dose that I got of caffeine was marginally less.
And then I just titrated myself up now and I just drink black coffee now.
So you're always, and you're, you're, you're putting a substance into your body
that your body hasn't seen or at a dose that is not used to.
So you're essentially just like mom said, your body is once maintained.
It, it's always trying to maintain.
And so when it's at the target, it's always trying to maintain.
So when it's out of balance, it's going to try to, so you're basically trying
to give it a small enough dose that it can maintain, and then you work your way up.
So, and you do this by a clinical trials and you figure out which doses are better
and which increments you increase by.
So you can give it to a population, but of course everybody's different and you
might be a little smaller like myself, and you might even need to start off with
it even smaller or even larger dose.
But your physician should be working with you on that one.
If you have these drugs,
we don't talk a lot about clinical trials in our podcast, but I did want to just
mention that there are definitely been studies with liraglutide or sex enda
that showed that not only did it improve blood glucose levels, which is kind of
for treating diabetes type two diabetes, but the mean weight loss that were seen
in these clinical trials with sex enda were 5.2 kilograms after a year of
treatment of weight loss, which is equivalent to about 11 pounds.
And it was a little bit less in adolescence and that was greater than placebo and stuff.
And so, but interestingly, too, 10% of patients that took this medication
discontinued it due to adverse effects, especially gastrointestinal effects.
And we're going to talk about that in just a minute.
And that's again the reason for this dose titration because these medications have
a lot of GI side effects associated with them.
Let me just get through the dosages.
Let me just get through the dosages of some aglutide and then we'll talk about
those adverse effects.
As Joshua mentioned earlier, the dose.
So ozempic is not FDA approved for weight loss, but so its doses are, you know,
for type two diabetes.
But there have been clinical trials that have used ozempic and weight loss, and
they've shown improvement in weight loss compared to placebo with doses anywhere
from 0.5 milligrams, that's the lower end, to 1.6 milligrams subcutaneously weekly.
Ozempic or some aglutide is dosed weekly, as Joshua alluded to, because of the way
the molecule was created.
So, Wigovie, the difference between Wigovie and ozempic are that the dosages
in the dosage forms are a little bit higher in Wigovie.
So you start out, and this, although you titrate with a dose of 0.25 milligrams
in the first week, actually for the first four weeks, you titrate it in 0.25
milligram increments over a 16 week time period.
You're targeting, you want to get to a dose of 1.7 to 2.4 milligrams on a weekly basis.
So, in the clinical trials that have compared some aglutide to placebo or to
other GLP-1 receptor agonists, primarily liraglutide, have shown that some
aglutide is the most effective weight loss agent that we have on the market to date.
You can lose about 14, almost 15% of your body weight with it.
So that's about 34 pounds.
That's just wild.
That's a 68 week treatment.
And that means, and again, remember, we're talking about in addition to changes
in your diet and exercise.
Yeah, we always say this is compared to placebo.
So people were still getting injected.
They thought that they were getting this drug, but they were just getting a placebo.
Right.
And then compared to the people who actually got the some aglutide, I mean, a 15 point,
what was the percentage?
It was 15%, almost 15%.
Amazing.
So 35 pounds, you know, and stuff.
So, but in addition, it also, some aglutide also provides significant improvements in
your blood pressure as well as your cholesterol readings as well.
And so, again, it has a mechanism.
See, these GLP-1 receptor agonists have mechanisms that help with controlling blood glucose and
also some mechanisms that help with controlling weight.
But they also have some mechanisms that improve cardiovascular outcomes.
They reduce inflammation in your system that contribute to cardiovascular, adverse cardiovascular
outcomes and some other things as well, too, lowering cholesterol as well, too, which also
has a negative impact on your, like, causing clogged arteries and things like that.
So lowering your blood pressure, all these things help you to have healthier outcomes
and stuff.
But there are more GI adverse events with some aglutide versus placebo.
And some of the studies, they've averaged, there were more GI, there were about 50 to
60 percent of patients had GI adverse events with some aglutide versus 10 percent with
placebo.
And three to four percent of patients would discontinue some aglutide treatment.
But some aglutide has been shown to be greater than loraglutide in lowering weight much more
significantly.
I believe the change in weight from baseline, so the start level when you started the study,
there was a change in weight of about 15.8 percent with some aglutide versus about 6.4
percent with loraglutide.
So it was almost twice.
So let me just mention these adverse effects that are associated with GLP-1 receptor agonists
because they have to do with the mechanism of the medication.
Remember I talked about the fact that it lowers, it slows gastric emptying and causes, like,
satiety or, you know, lowers your appetite and stuff.
And so because it does the slower gastric emptying, so it, and because the GLP-1 receptors
in your brain affect your appetite, it can cause nausea, vomiting, constipation, and
diarrhea.
And there can be some, you know, in kind of the package inserts, the kind of the conglomerate
of information as far as percentages that these things are seen in is that you can see
about 39 percent nausea in sexinda, which is loraglutide.
You can see about 44 percent incidence of nausea with Wigovie.
With Ozempic, the data that I could find, it was between 15 and 20, but those were lower
doses of Ozempic than the higher doses of Wigovie.
Diarrhea the same, it's 20 to 30 percent with sexinda and Wigovie versus 8 to 9 percent
with Ozempic.
Constipation, 19 to 24 percent vomiting, 15 to 24 percent with sexinda and Wigovie.
So these GI adverse effects can be problematic for patients.
I have known a couple of people that have tried to take Ozempic for either type 2 diabetes
or for weight loss associated with diabetes, type 2 diabetes, and they can't tolerate it
because it causes too much nausea and vomiting.
So it's patient independent.
Yeah, I wonder, do you think that's due to the dosing or is it due to?
This was at the lowest dose.
I think it's just that everybody's different and they just can't.
You get this signal to your body as far as just nausea and stuff and some people just
can't handle it.
I just wonder if there's a point, I don't know if we have any literature of like if
you push, if people who did experience nausea, if there was a point at which that nausea
stops, you know what I mean?
Because like you said, if your body is changing, that might be that your body's defense.
I don't know if there's any literature.
In some patients that does happen, so they may experience the nausea, but it's tolerable
to begin with and then they develop it.
It's uncomfortable to begin with, but then they develop a tolerance to it and then there's
just that percentage of patients that can't for whatever reason.
Sometimes you might be able to, pharmacists really, and I can't speak for physicians,
but pharmacists really don't like to treat an adverse effect with another medication,
but if you really needed this, there's the potential that you could treat with some anti-nausea
medications and see if you could tolerate these agents, but that's going to be with
your physician just kind of working through that.
So just know that I think one of the reasons that, and there's some physiologic reasons
behind why these agents work to lower weight, but there's also, so due to that mechanism
also is there's some adverse effects that also are contributing to that as well too.
Because if you don't feel like eating, then you're not going to eat and stuff.
So then sometimes that's good and sometimes you still need nutrients in your body as well
too.
Yeah, 100%, but I think a lot of times like you said, I mean your body's going to get
those nutrients from somewhere and they're probably using the glycogen stores and they're
also using the fat stores that are in your adipose tissue.
And I assume, I don't know a lot about this physiology of going from different fuel sources,
but I imagine going from a purely glucose driven fuel source to one that's either driven
by fat or by glycogen probably does feel different in the body.
And I wonder if that transition is part of the reason why people feel this thing.
Because I'm of the firm opinion that a lot of this is due to the fact that a lot of the
calories that you would be eating are not being eaten.
And I think when you look at people who consume an optimal amount of calories, which is the
daily diet, which is like 2000 a day on average.
And if you're used to eating 3500 a day, that is a 1500 calorie difference.
And of course that's going to have massive effects in your body.
And I think it's hard to parse which of these are related to actually taking the drug versus
is the drug preventing you from eating in mass excess that would cause these lowering
of the blood pressure, lowering of blood glucose, et cetera.
And I think it can do that.
I know I, my personal experience is not with Ozempic or with Wigovie, but years ago I took
a medication to help prevent migraine headaches.
And one of its adverse effects was it caused kind of satiety or you know, you've, you know,
not, you know, you loss of appetite and it really did cause a loss of appetite due to
its mechanism and it's neurologically based in your brain.
And so, you know, I lost several pounds and I don't necessarily need to lose several pounds.
But if I took Ozempic, I don't know what would happen to me.
So, you know, so I think there is definitely a physiologic reason behind why people don't
eat as much when they're taking one of these medications.
Yeah, no, I totally agree.
I think what I was pointing to is like some of the positive health outcomes, how much
of what percentage could you give to the drug itself versus these, like, for example, we
always say the exercise is like the fountain of youth, right?
So like running itself isn't good.
It's all the things that running does inside of your body.
And obviously when you're running, you don't have time to eat.
Right.
So it's like, right.
Or you change.
Yeah, you change your, which parts of these things are contributing.
And my guess is that the majority of the benefits from these drugs are the fact that you're
not eating as much as you normally would.
Just because, yeah, when you, when you, especially if you're a person who is overweight or obese,
I could even speak to this myself because I've definitely been in times in my life where
I've been, I've weighed more than I do now.
And when I eat less, for some reason during the pandemic, I ate a lot less and I lost
a lot of weight.
And, and so I just, I just felt better.
I just had better metrics all around and, and I don't even know how it happened.
It just, you know, the pandemic was weird.
I think it was because I slept a lot more and I was just, I didn't have a lot of stress
in my life because I didn't know anything to do.
So there was, there's something really interesting about that when you take away that urge to
eat and that always consuming calories because food is so palatable.
I mean, it's so delicious.
We're about to go have lunch after this and it's going to be great.
So we just don't want to eat too much of it.
Well, and you think about too, when you exercise, you, your body is generating heat and utilizing
calories and, and burning off fat and stuff, so it is going to change your, your,
But the amount that you would have to exercise, like for example, if I went for a run, I might,
let's say a 15 minute run, I might burn 200 calories.
I could get all that back in a chocolate chip cookie.
Absolutely.
So it's, most Americans, I think the recommended exercise is 15 minutes a day for a week.
Most people don't meet those requirements.
So it's like the idea that we're going to beat this epidemic with exercise is, I just
don't think it's ideal.
I mean, it's idealistic.
I would love that.
People have kids, they've got jobs, they've got lives.
Or it gets stinking hot.
And it gets, yeah, here in Texas.
But some people just don't have the time to donate.
There's a lot of these influencers out there who are like, oh, you just got to go to the
gym and these people are in the gym for like an hour or two.
And I was like, these are single people who probably don't have many other responsibilities
other than getting on social media saying you should be more fit and shredded like them.
And it's just not practical.
So this seems to be like a tool more for most people who they've tried everything, they've
tried exercise, but within the limits of their life, they need something more practical.
Right.
And again, remember, we're talking about people that need these medications for weight loss
are going to be those that have tried other mechanisms.
And it's a really serious condition that they've got here.
Right.
I agree.
There are some contraindications for these GLP-1 receptor agonist uses.
What's a contraindication?
Contraindication is that you shouldn't use it.
You shouldn't use it.
So like if you have pancreatitis or pancreatic issues, issues with your pancreas, you shouldn't
take it because that's part of the mechanism of the medication to release insulin from
your pancreas to lower blood glucose and stuff for the diabetes part of it and stuff.
So kidney disease because it gets eliminated by your kidneys.
So if your kidneys aren't working well, then you could increase your side effects from
the medication if you've got to, you know, you won't get rid of it.
If you have type 1 diabetes, these medications are not for that.
So they don't...
Yeah, because type 1, your body literally doesn't have the genetic capability of making
insulin.
Right.
So that whole mechanism is just kaput.
Whereas type 2, it's brought on by behavior.
A lot of different factors, yes.
And you can bring that back with lifestyle and medication.
Right.
If you have diabetes-related retinopathy, that's an eye condition, that's an eye irritant.
And so if you take these drugs they found in some of the clinical studies that it actually
increases the risk of this so that they shouldn't take it.
Every clinical trial, every package institute will tell you that if you're pregnant or breastfeeding,
you can't take it unless it's been proven in it.
And so if you're younger than 18 years of age, although that's not... that really shouldn't
be there because we do have some of these agents that are actually indicated for kids
less than... that are 12 years old and older.
Yeah, I agree.
And then there's...
That will probably change over the next 5 to 10 years.
Right.
And then there are some weird conditions, medullary thyroid cancer and multiple endocrine
neoplasia.
You'll hear those on the... when you listen to the way Govee add on TV, they're just some
weird cancers that if you have those then you shouldn't take these drugs.
So as I was preparing for it to come up here, because I live in New Braunfels and Josh lives
in Austin, Texas.
And so I was thinking about this the other day and I thought, oh yeah, we need to really
talk about what happens if you stop taking a GLP-1 receptor agonist?
What happens to your weight?
Is your weight maintained?
What happens?
And so I looked at that, this a little bit.
And so there have actually been studies that have shown that patients can regain their
weight after they stop the medication.
And again, you think about the mechanism behind the GLP-1 receptor agonist.
And so it hasn't been actually documented clearly why this happens, but that it could
be that you then end up with a hormone imbalance.
Remember, those increments are hormones.
If you're not putting those GLP-1 receptor agonists in there to help kind of mimic that,
then there's an imbalance with those when the drug is discontinued.
Yeah, we should mention like an agonist, that word means that it's a molecule that has an
affinity for a receptor that your body naturally creates a protein or molecule for.
So I think it's 90% similar to the other one.
So that means that it binds really well with this receptor.
So if your body's seeing that this other thing is binding to it, it might just say, hey,
we're not going to make the natural one anymore because like it's already the, your body has
all these feedback loops inside of it.
So this could be a potential mechanism for why that rebound happens.
Why you start gaining weight after you stop.
Absolutely.
It also could be that the cells in your central nervous system or in your brain, they forget
how to regulate weight gain in the absence of these GLP-1 receptor agonists.
So again, they could kick back in and then you've got the whole like, you don't have
fullness anymore.
You increase appetite stimulation and stuff.
And so it could compensate for that.
Or your beta cells in your pancreas could malfunction and they could start, they could
produce, or they could not produce insulin.
So you would increase with more glucose and substance so you could gain weight that way
because it will turn into fat.
Or interest, this was interesting too, your gut microflora can be changed.
Studies have shown that your gut flora or your gut, the bacteria inside, we all have
natural bacteria in our gut.
They do good things for us and stuff.
And so if they, and they've been, it's been shown that these, and that the GLP-1s and
as well our regular gut bacteria can help us to feel full and help us to have blood
glucose is maintained and stuff.
And so if you, and it comes by GLP-1 secretions.
So if the more GLP-1 there is and the more this happens with these gut bacteria, so if
you pull the GLP-1 receptor agonists out there, then they're going to stop doing that as well
too.
None of this has been actually proven.
Yeah, these are just potential.
And I did see one study, it was, forgive me for not exactly remembering all the exact
details, but it was comparing, I believe it was loraglotide and exercise and then both
of them together.
And then you stopped them.
And what the studies showed that was that, I believe it was like that you had more weight
loss maintained with the loraglotide and, but weight gain, I mean, I'm sorry, I think
I said that wrong.
Let me, let me do that again.
So loraglotide and exercise and then loraglotide plus exercise.
And what was shown was that if you exercise, it maintained your weight loss maybe as much
as, well, maybe not as much, but better than loraglotide alone.
I think it was loraglotide and exercise compared to exercise and they did better at maintaining
your weight loss, but you still do gain some weight back after the drug has discontinued.
Yeah.
And I think that makes a lot of sense.
They even did one where they had a cohort study where they put a certain population
on some aglotide and one on placebo and then they switched them mid.
And you just literally see the graph flip where so the people that were losing weight
and they got the placebo, they just gained it right back.
So you, again, I'm, I have an opinion and this is just my opinion, but it's like, if
you don't have those satiety signals being sent anymore, then you're just going to eat
again.
So if you don't have, I kind of view eating kind of like drug addiction.
I mean, food is so good because it releases, I mean, our brains are just designed to have
these dopamine receptors that respond really well to food because it's, dopamine is this
anticipation of reward and reward means that you live because eating food is good for you.
So you, so you're, you're basically your body, your body wants this stuff and you want
this stuff because most of the time food is good, but too much is bad and your body doesn't
know that because it just wants more.
So if you don't have these compensatory mechanisms like exercise or, you know, basically knowing
your buying patterns of like, okay, maybe I should have half as much in my fridges as
I, as I normally do.
Or, and I've talked to some friends, this is all anecdotal evidence, but once they were
on these drugs and then they went off, they still felt their appetite come back, but they're
like, well, I know I can live on less.
Like there's this, like this idea that you need to eat as much as you did.
And then when you have this experience, like, Oh, I was totally fine eating almost nothing.
So obviously you have to live between those extremes.
So for me, I think a lot of this is, I think the common root of a lot of this is just people
who overeat and we can talk about the gut microbiome, but we don't even know what bacterial
species are good or bad.
We know it's good and we know it's bad in some regards, but to tailor make it for us,
we're not, we're not that air.
We just don't even know what species are, you know, are, are good in certain environments.
So I think, I think a lot of this is, is yeah.
Can you get on it very much like you would try to wean somebody off of a narcotic.
Let's just use opioids, for example, with Narcan.
And then you would try to get them into behaviors and having coping strategies so they wouldn't
want to reuse again.
Yeah.
We're just, we're just stimulated by a lot and to have strategies to be able to deal
with that stimulation is tough.
But I think this is such a great tool to help people start that journey.
So I would really like, hopefully over the next five to 10 years, we study people who
maybe go on and off this and which strategy is going to be the best to, I don't want
people to be on this forever.
Right.
And it's very expensive too.
So yeah.
Um, and I, so it's like, what is going to be the best combination of like use versus
behavioral intervention that's going to help people not just keep weight off, but like
you want to encourage people to exercise and, um, because exercise is just such a great
tool to have a better, longer life.
Um, especially when you're later in life, because you just lose a lot of cognitive ability
and when you get older and to be able to exercise really helps stave off a lot of that.
I would just, I would just, um, modify that a little bit.
If, if you are taking a GLP one receptor agonist, not only for weight loss, but for, you know,
improving cardiovascular events or reducing the risk of cardiovascular events, or you've
got type two diabetes, then it will be a lifelong medication, you know, as well.
I mean, unless you need to modify your treatment for other things, but yeah.
So there are some patients that would actually need to take it lifelong and stuff.
So, but yeah.
Well, I'm going to ask your opinion on this.
Um, let's assume that we have an infinite supply of these GOP one agonist.
Do you feel like it would be okay for folks who are not obese or, or have type two diabetes
to use them?
Well, I, um, no, because I mean, well, I guess, let me take that back.
Based on the literature and based on what studies have been done and based on how the
food and drug administration have approved these medications, there's no indication that
they should be used for someone that's not overweight or has obesity.
It's for those three indications, depending on which medication you're looking at either
for unless they need improvement in cardiovascular events.
And there are a few that are approved for that, or you've got type two by diabetes,
or you've got a weight weight issue.
So I don't know why you'd want to take it otherwise, you know, and so I think some people
and I think this gets to prevent weight loss.
I mean, to prevent weight gain.
I would think that's, I think, I think that would be a very expensive and potentially
unpleasant, you know, or uncomfortable way to do that.
I think exercise and modifying food would be a whole lot better, but that's again, just
my personal opinion.
Yeah.
So, so if someone, let's just say that they, they have a poor body image of themselves
and they think that taking this is going to shave off that, that, you know, three to five
pounds that you want to have, so they take this.
So you would say probably not a good idea.
No, I think that they need to, you know, get with some friends or if they need counseling
or whatever, as far as just like, let's get, let's get that, let's get an improvement
in, in, you know, how you're viewing life and how you're viewing, you know, yourself
and stuff.
And this whole crazy thing of, you know, I mean, not certainly struggle with that as
far as, you know, oh my gosh, I gained a pound.
You know, it's like, but it's crazy.
You know, a couple of pounds, we're going to, you know, fluctuate and stuff and that's
just the way it is and stuff.
So, and so we always end our podcast by talking about the common myths or misunderstandings
associated with the medication that we're talking about.
So today we're going to talk about the common myths or misunderstandings associated with
GLP-1 receptor agonists and weight loss.
First one is that GLP-1s are a new class of drugs and that's not the case.
They've been around for over 15 years.
So it's not like it's a new medication.
It's just that we've kind of narrowed in on this particular aspect of it, of weight loss
that's been available since the beginning of it.
Now the second one is that Ozempic is FDA approved for weight loss and hopefully you've
gotten, you've gotten that, you've gotten, you've figured out or you've been, it's been
reinforced that Ozempic is not FDA approved for weight loss, but studies have been used
to show it can be effective for weight loss.
But Wagovi is the semaglutide form, form that is the FDA approved agent for weight loss.
Yeah.
And also just because we've, we've, we've been using it for 15 years, we also have pretty
good longevity data of that.
It's relatively safe and effective.
There's not a lot of long-term consequences are going to be caused by this.
And then the third one is due to shortages with these medications that people with type
two diabetes may not have access to Ozempic or loraglutide since, since providers are
prescribing them for weight loss.
And it's possible, but because there is that free tracker, it's, I think it's useful in
helping you find out where these medications are available in your area.
Might have to take a road trip.
So, or get it shipped to you.
Yeah.
That's also true.
The fourth one is that taking a GLP-1 drug will guarantee significant weight loss.
And it's not necessarily true.
Most, most patients will have weight loss associated with these medications, but there
is a small percentage where it doesn't work.
So it's patient specific.
So darn thing with averages, like you want to assume that you're probably going to be
one of the people in the average, but you could be on either side, you know, either
with significant weight loss is not a lot or a lot.
And remember too, it takes time.
You know, it's not, you're not going to lose 35 pounds in one week.
You know, it's, it's over usually a year or so that you're looking for this, this,
this overall weight loss.
And you have to be consistent with your treatment.
Absolutely.
Yeah.
The next ones are that you don't have to change your diet or exercise.
And when you're taking a GLP-1 receptor agonist, and that's not true, remember that all of
these agents were approved in conjunction with a modified or improved diet and improved
exercise.
Yeah.
Even if you look at the placebo arm of these trials, they'll actually show that the people
who got placebo, they got health and nutrition diet advice.
And they also, in average, like around two, two and two and a half percent of their body
weight.
So even with someone telling them this advice, there's something called the Hawthorne effect,
which is this idea of like when you're being observed, you behave a lot better.
I experienced this when I was at home as a kid with my mom.
Not always.
I was an angel when she was watching, but then whenever she looked away, yeah.
So there's this idea of like being monitored really helps you do better behaviors.
So obviously we did that in both groups, but the drug was much more powerful.
But this idea that, yeah, actually it does have an effect.
It's definitely not as pronounced, but it does help.
Yes.
The next one is that the side effects to GLP-1 receptor agonists are either unbearable or
no big deal.
And there's no way to put a label on that and the impact that the medication is going
to have on every patient.
Everybody's different.
So some people are not going to be able to tolerate it, even with modifications in dosage
or slower titration.
And some people are going to breeze through it and have no problems.
So it's patient specific.
The next one, and Joshua alluded to this earlier in our conversation about using compounded
forms of GLP-1 receptor agonists and that they're just as safe as brand name medications.
And that is not necessarily true.
Remember the brand name medications are Food and Drug Administration approved.
And when you have a drug that's approved by the FDA, that means they've gone through rigorous
trials.
They've looked at safety as well as efficacy.
That's why it costs millions of dollars to get a medication approved because they've
got all these trials that they have to do.
So compounded drugs don't go through that same rigorous evaluation strategy.
And so a compounded medication may have either more drug in it than is labeled.
It could have less drug in it, way less drug in it, no drug in it.
You don't know.
And the other thing too is that you could get a different amount every time you get
a compounded medication because FDA approved medications are created and manufactured so
that they are pretty much the same, plus or minus 10%, the same amount of medication in
every dose.
And that's not the same thing with compounded medications.
So if you get a compounded GLP-1 receptor agonist, you could get really sick with one
dose and not so much with another.
Or you could see some good effects one week and not so much depending on how much drug
is in the medication.
So yeah, that's such a good point.
I mean, not to incriminate anybody, but anyone who's ever bought an illegal substance, whether
it be marijuana or mushrooms or cocaine, the danger in all of those is that you don't know
where they're coming from.
And as we've seen with the recent opioid epidemic, we have things that are laced with things
like fentanyl.
And fentanyl is 50 times more potent than a standard opioid.
And if you take that thinking that you're going to be taking a standard just, you know,
Quaalude, then you could die.
And a lot of people have.
So the idea of, I know there are a lot of people who just don't like regulations, but
regulations are the idea of you have a standard operating procedure so that there's a realm
of consistency in the product that you're getting.
And a fun anecdote, there's this great book out there.
I can't remember the name of the book, but it was basically saying like this author basically
went throughout the world and said thank you to every person who was a part of the supply
chain for coffee.
And you just interact with hundreds of people.
There's so many people involved in a cup of coffee.
But one of the things he mentioned was back in the day, coffee, when it was getting popular
as a alternative to tea and other beverages is that a lot of coffee manufacturers would
actually stuff the grounds and they would basically fill it with other things.
So if they were selling you a bag of coffee, be like, oh, we have this amazing coffee,
but maybe 20% of it was coffee.
And the other stuff was just like maybe rat hay or rat droppings.
Like it's this idea, like they do exactly the things that compound pharmacies are doing
now.
They'll just fill it with other things and they'll call it the standard thing because
they're not being regulated.
They're there to make a profit and also undercut the price against the competition.
And if there's no one there to say, hey, you're actually selling me a bogus product, and there
are compound pharmacies out there that do operate under the FDA procedure, but it's
technically not legal to do that outside of a prescription.
So you just have to be mindful of that when you're taking, if you're buying drugs from
a compound pharmacy.
Right.
The next one is that your insurance is going to cover the cost of your GLP-1 receptor agonist
if you are a prime candidate to receive that.
And that's not necessarily the case.
We talked about the fact that Medicaid and Medicare patients, they don't cover, Medicaid
and Medicare don't cover these for weight loss.
And then it just depends on your insurance as to how good it is as to whether or not
they'll cover this, especially for an off-label use.
Another myth is that all GLP-1 medications are the same, and we've shown that that's
not the case.
They're similar, but they're not identical.
The next one is that, and Josh alluded to this by the fact that these agents have been
around for a long time, these GLP-1 receptor agonists.
There used to be some anti-obesity medications that caused severe cardiac problems.
They were Redux and FenFen.
They were from, I think the 1990s, I think.
And those are stimulants, and so they would cause things that go along with the stimulant
as far as heart racing and myocardial infarction and stuff because of just that stimulant effect
that stimulants have on the heart.
But that's not been the case with GLP-1 receptor agonists.
They have been around and they've not shown any life-threatening events.
There has been some, the thing that has been noted primarily with the heart is there can
be some increases in your heart rate, but not the significant adverse events that we're
seeing with those agents from the past.
And the last one is that sometimes people will receive bariatric surgery for being obese.
You know, that's your gastric stapling, those types of surgeries and stuff that help to
also provide satiety by, you know, limiting what goes into your stomach.
And so if you have that surgery, it talks about that you might not need medications
to maintain weight loss, and that's not necessarily the case.
It may be that bariatric surgery is done in conjunction with other things as well, too.
So to wrap it up, we've seen that semaglutide and loraglutide are effective in weight loss
in addition to being agents that help to control blood glucose and type 2 diabetes mellitus
with semaglutide having greater efficacy.
They're not for short-term weight loss.
That's not what they're approved for use for.
This is long-term.
This is over a long haul, you know, because it took a long time to get here.
It's going to take a long time to manage this, and it's just something that needs to, you
need a new paradigm shift in how to manage your weight, and this is one way to help get
that done.
It's not, these agents are not without adverse effects, and they are to be used in combination
with lifestyle modifications.
They are expensive.
And there are other medications that are available to help with obesity that are not quite as
pricey.
They may not be quite as effective, but there are some other agents that are available as
well.
And not everyone is going to need a GLP-1 receptor agonist to manage obesity as well,
too.
Yeah, I mean, this is such a great comprehensive overview of these agonists.
I mean, I just, I'm so, this makes me so hopeful because we've just seen obesity rates, not
just in America, but across the world, really skyrocket.
And to have a tool like this that could potentially help people, I just think is really powerful.
So, I mean, if you told me, like imagine if I was 300 pounds, and you said for $15,000,
you could lose potentially 10 to 20% of my weight in a year.
I don't know, that sounds like a decent price to pay, but of course, everybody's different,
especially people who are poor.
They probably can't pay for that.
Right.
And I think also as citizens of this country, it's like, should we pay for that now?
Like we're talking about for Medicaid, right?
Yeah, Medicaid, Medicare.
Yeah, Medicaid's for people of the lower social economic.
And Medicare is for older people.
So for, it almost just seems like that would be a great low-hanging fruit to help people
in that status.
Even if you don't help all obese people, like if you just help people who are poor who have
this condition, I just don't know.
I mean, that would be relatively expensive.
Right.
And then where's the money going to come from?
And which part of the pie from the governmental funds are we going to take it from?
And it's just one of the, it's just complex.
Right.
But if you're, I think that you just have to make sure the math works out.
It's like, if you're already paying for it in the healthcare system, then it's like,
well, we might as well just pay for it upfront or even pay a little less, you know, to maybe
offset that.
Like, I think a similar thing is like, I'm sure we give people statins for blood pressure
and it's like we-
For cholesterol.
And we give that to them because we think it's a good thing to-
Studies have shown that it's beneficial.
And we pay for that because it's going to prevent adverse effects in the future.
So I just think we need to get to a conversation where this, if these drugs turn out to be
as powerful as they are, which they seem to be, that this seems to be one in our arsenal
to fight chronic disease.
But I wanted to ask your opinion about, we were talking a little bit earlier about people
being overweight.
And we talked a little bit earlier about people taking it who weren't overweight or weren't
obese.
And I wanted to get your opinion on why you think people, if they kind of freak out if
they gain a pound or if they lose a pound, like where that kind of comes from.
Is it a cultural thing?
Is it a gender thing?
Like, what is the reason why you think that people who seem relatively healthy or relatively
thin, they would like to take these medications to shave off a couple pounds?
And I think that with me being in my 60s, I don't hear a lot of 60-ish year olds taking
this for body image.
It's going to be more for health reason.
So you would have to speak more to the 30-ish year old and stuff.
But I'm thinking from a female perspective, I think it's like what you get fed as far
as what we look like has gotten drilled into us since we were little girls.
Or I guess probably middle school, adolescence, that type of thing.
And being OK with how you look needs to be OK.
And so those fluctuations, our body weight fluctuates and stuff.
But just you get like that either through movies or social media or friendships or
proposed friendships or purported friendships or relationships with guys or whatever, as
far as just what they tell you as far as how you look or whatever and stuff.
And so I think that you've got to be OK with who you are and stuff and not let it dictate.
So much easier for me to say that now in my 60s than when I was in my 20s or 30s and stuff,
because you get so influenced by who's around you and what the message is being said.
Well, that's a good point.
So obviously, we hope that some of these young women and men will be in their 60s one day
if they're not already.
So this is some wisdom that you can pass on to them.
So if you could tell your younger self a little bit of advice, because it seems like what
you're talking about, there's a way to look at your weight in terms of health and there's
a way to look at weight in terms of your aesthetics or how you present to other people.
And it seems like you're saying like actually focusing on your health is so much more important
than the aesthetics, because the aesthetics is like how people see you.
And do you want people to only associate you with how you look rather than the content
of your character?
Great, I would agree.
OK.
And it's you.
It's like, you know, a few pounds is not going to change your clothing size.
You know, it's not and stuff.
But so I'd say that if you had to buy a whole new wardrobe, that could be like a factor
as far as how much weight you've gained and stuff and all that.
You know, it's just it's like.
But I'd say for for the whole, I think it's just a matter of, you know, being OK with
how you're created, realizing, too, that as you do get older, as the decades pass, you
know, your body does slow down and burning out burning up fat.
And you just you either modify how you eat or you get you get used to having a few extra
pants to carry around, you know, and stuff.
So yeah, yeah, that's a good point.
So yeah, yeah, I totally agree.
I mean, on the younger side, I think, at least for me personally, there's an association
with like you want life to be a little bit easier.
So like you just notice that pretty thin people just get more attention and you notice that
they get maybe more opportunities, doors open for them easier than somebody who's not.
And to compensate for that, like, for example, I learned to play guitar and sing because
I was like, well, I have to get girls attention somehow.
So I can't just be this tall strapping guy.
So I had to actually was a benefit that I that I didn't do that because I wouldn't
have had the skill that I have today.
But I think there is this kind of desire.
And I think it's a foolish desire to think that life will be better once it's easier.
And I think when the more the older I get, actually, the more difficult I shouldn't say
difficult, but the more challenges are the way that you learn.
You know, you kind of push yourself actually makes life a little more interesting because
if everything came easy to you, there would be no incentive to learn and to grow and to
and to be a modified version of yourself because people just give you free stuff just for being
you.
So it almost seems like a bit of a curse, even though it's a very alluring curse for
things to wanting to be easy all the time.
And I think my generation, probably the generation below me, is growing up with the Internet
where everything's kind of instantaneous gratification.
Like you can just if you're pretty, you can just post a picture online and just get strangers
telling you that you're beautiful.
And that's going to be intoxicating and scary and scary, especially I imagine as young women
who they probably want attention from a certain percentage of those admirers, but not for
most of them.
I think it's true of most of us.
So it's this really interesting tightrope of going to like, how much of life do I want
to be easy versus how much do I want to be challenging?
I think too, with being overweight or obese, too, if you're able to shed a few pounds
or if you're able to just keep your weight in a good range, I mean, your mobility is
improved and just you can breathe better.
I mean, just just natural things happen versus, you know, getting up and out of a chair is
going to be easier and stuff.
And it's I mean, it's like, again, we again, we go back to the fact that obesity is a metabolic
disease.
It's not necessarily just a behavioral choice.
And so it's just a matter of, you know, there are things that you can do to help go in a
positive direction.
We've got so many more tools now than we used to have.
That's a really good point.
Yeah.
And then to use those tools to help folks like that have a better quality of life, right,
which is what life's all about.
There you go.
Yeah.
They can go have lunch with their mom.
There you go.
That's right.
Well, y'all, thank you so much for joining us today on a really interesting and hopefully
fun topic that you found educational.
And we'd love your thoughts and what you think about these drugs.
And if you're even if you're taking them, we'd love your your experience just to hear
what it's like, because this is definitely a new frontier in terms of medicine.
So with that being said, my name is Josh Klaus and I'm Jennifer Seltzer.
And this has been another episode of Your Mom on Drugs.
See you next time.