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Let’s talk GLP-1 Receptor Agonists for Women's Health
Recorded: April 22, 2025 Duration: 0:42:28Space Recording
Short Summary
AthenaDAO is set to launch groundbreaking initiatives in women's health tech, focusing on wearable devices and biosensors, while highlighting the growth potential in the sector as innovative treatments gain traction.
Full Transcription
Thank you. All right, thank you so much for joining on this new link.
We'll go ahead and get started since we're a little bit past the hour now. So I'll just quickly give an introduction to what is Athena Dow, give my background, and advocates working to advance women's health research, education, and funding.
If you don't know, my name is Jenna, and I'm a science and dual flow lead at Athena Dow and have been with the Dow for about a year and a half now.
My background is in molecular biology, and more specifically, I studied longevity.
In the longevity space, I noticed a lack of conversation about women's longevity.
And so, yeah, since then, I've basically been interested in any and everything women's health.
So, yeah, with that, I'll let you take it away, Dr. Beverly,
and we're very excited to hear your insights today. Thanks so much, Jenna. Really excited
today to talk to you about what is needed in the next era of women's health. My name is Beverly
Chang. As you said, I am an endocrinologist and weight management specialist as well at Weill
Cornell in New York. But I do have a particular interest in women's health, particularly
menopause, polycystic ovarian syndrome, fertility, kind of all of those pieces. And I will overshare a little bit that I myself am a millennial.
So anyone in that 30, 40, closing to 50 age group, I think I can particularly empathize with whatever kind was just, I'm sure you all have seen some
headline in the past few years or maybe you or someone you know has taken a GLP-1 receptor
agonist.
It is a little bit of a controversial subject, so definitely want to make sure that the conversation is grounded in the science and the facts of all the research that led to, um, this, uh,
this huge, uh, growing interest we see in GOP ones now, but, but basically, um, originally they
were indicated for, uh, type two diabetes and, um, then expanded into, um, obesity. And now we're seeing that they can be used for so many different indications.
Like every day, it seems like new research is coming out about how they can manage everything
from substance abuse to preventer degeneration and especially women's health which is the the focus of today so
um yeah dr chang if you could give us oh and before before i get started i just want to give
it a disclaimer that everything you hear today or nothing you hear today is medical advice so
please if you have any questions specifically about your journey, please consult with your
care providers.
And so, yeah, with that, we'll get into some background.
So, for Dr. Chang, just wondering if you could give us an overview of some of the research
that led to these first clinically approved GLP-1s and let us know how these GLP-1s
work. Yeah, absolutely. So I think Ozempic is probably a household name now and the hashtag
went viral in 2019, 2021. I don't quite remember now, but these medications, which fall under the category or
umbrella term of GLP-1s, have really been around since early 2000s. So the very first one was
approved in 2005. We're 20 years in, two decades in now. But in 2005, the first GLP-1 was called exenatide,
and that was indeed approved for type 2 diabetes. And so over the past two decades,
research in this field has developed to figure out what can we make better GLP-1s? In other words, can we control diabetes with fewer side effects,
with an easier pen mechanism, make it easy for people to administer it? And as a side project,
I suppose, they've discovered that some of these GLP-1s were quite good at causing weight loss as a side effect.
And so one of the other GLP-1s, Sixenda, which is liraglutide, was approved in 2014 for the treatment of obesity specifically.
Prior to that, it was approved for type 2 diabetes, but then a few years later,
it was approved for weight management even in people without diabetes. And so since then,
we've now seen increasing activity in the research space and further interest in the GLP-1s,
where now we have semaglutide, known under the brand names of Ozempic and Wagovi, as well as terzepatide
known under the brand names of Monjaro and Zepbound, which also treat both diabetes for
one indication and then for obesity or overweight in individuals for the second FDA approved
indication. Now, Jenna, you mentioned
that there is a lot of interest in research in its use for other indications. And I'll add that
both Ozempic and Wagovi are also on label for people with cardiovascular disease. So they are
FDA-approved for heart problems. If you've had a heart attack or a stroke,
or if you have something called peripheral artery disease,
then these medications are also approved for that on label.
But the exploration into dementia or fertility
or a substance use is still in that exploratory research phase and definitely a very exciting
frontier for us.
Yeah, thanks so much for sharing.
It's really interesting to me to look at the story of the research that went into the GOP ones that we see today.
Because I was just reading that, I guess, researchers originally,
they started studying glucose regulation and looking for treatments for type 2 diabetes
quite a while ago, I think almost a century ago. And it took decades and decades of research to
get to identify like the GLP ones. And there's even one story that maybe some are familiar with,
but there was a researcher who was curious why this glial monster, this lizard,
I guess, would not eat as so frequently. And so they studied the venom of the lizard and
they found a GLP-1 that had a longer half-life than what was found in the human gut. So
had a longer half-life than what was found in the human gut.
So it's just wild to look back and see sometimes how long this research takes to be translated.
And it seems like the big driving factor behind the GLP-1s we see today is the improvement of the half-life of these molecules because our GLP-1
is a naturally occurring peptide in the gut. But the big difference between the naturally
occurring one and the GLP-1s that we see today is really the half-life. And yeah, Dr. Chang, you've mentioned some other different GOP-1s because we have the
ones frequent, I guess, frequently used today are semaglutide, trisepatide, and then some
may have heard of retitrutide, which is in clinical trials now.
And it seems that they're all becoming more and more potent. So
trisepatide is a dual agonist and redditrutide is a triple agonist. So just curious, Dr. Chang,
how, I guess, how much, because with each of these, you get increased amount of weight loss. So just curious, what do you think is the
upper limit and how much can these drugs be improved from here? Gosh, that's such a great
question. And, you know, it kind of gets into exactly how it works. Thank you, Jenna, for the
background. It's interesting because, yes, it was the GLP-1 hormone was first discovered in the saliva of a lizard that, yes, they call it
the Gila monster, G-I-L-A, Gila monster. And that was discovered back in the 1990s. But which kind
of informs us too that all of our pharmaceuticals, all of the drugs we have nowadays typically have their roots in nature, right?
We go out, we look at the red yeast rice for statins, which is for cholesterol, or we look at the lilac, English lilac plant, and figure out why is this beneficial for glucose control.
figure out why is this beneficial for glucose control. And then years later, we find out
and purify the substance that now is known as metformin, which treats type 2 diabetes. So
similarly, we are often inspired by what nature is doing and working to refine that to make it safe and effective for humans. The way GLP-1 works is
exactly as it works in the Gila monster. It suppresses appetite. And it does so through
primarily activating your, or rather suppressing your appetite center in the brain. And the brain
appetite center in the brain. And the brain has an area called the pituitary gland, which is our
master control center for, oh, sorry, not the pituitary, sorry, the hypothalamus. It has an
area in the brain called the hypothalamus, which is our master control center for a lot of
regulatory processes.
So things that we don't think about,
like our body temperature is controlled by our hypothalamus
and our circadian rhythm is also controlled
by our hypothalamus.
The hypothalamus also controls our weight.
And you may have heard of this common term
called the weight set point, effectivelyively, you know, where your body
wants to be at any given time in your life, that might be lower when you're in adolescence,
it will certainly be a higher set point when you're pregnant. And ideally, it goes back to
whatever your quote unquote, normal set point is after pregnancy. But in the case of obesity, we find that there are problems
with that area in our hypothalamus where our body weight set point keeps getting pushed upward
for some reason, number one. And number two, that hypothalamus is also dysregulated when it comes to food
relationships. So we have a problem with maybe feeling full. Some people go through lives,
through their life, never having actually felt full. Okay. And they always feel hungry.
Or you have food relationships where it has nothing to do with hunger, right?
It has to do with whether the food is in front of you or not, or perhaps you've been socially
or culturally trained to always finish your plate or to eat at specific times of the day.
I'm on the East Coast.
It's 12 o'clock right now.
I'm told this is my lunch hour, so I should be eating lunch, right?
And it doesn't really matter whether I'm hungry or not, but that's what society has trained me to do.
And all of that gets away, I think, from what our biology is supposed to be,
and I think has contributed to the weight problem, both individually and nationally or globally.
both individually and nationally or globally.
What these medications do, the GLP-1s,
is it tries to reverse some of that
in the sense of getting your brain resensitized
to those hunger and fullness cues.
So it does suppress appetite.
It makes you feel full to the point that when you're full,
you are full. It doesn't matter if your plate is not clean. It doesn't matter if everyone else is
still eating around you or it's time for dessert. You're full and the medications force your brain
to recognize that. And in terms of, I'm sure you guys have heard of the word food noise or the term food noise.
What we're realizing now is that these medications may actually affect other pathways in the brain
where people might have these emotional or social relationships with food that isn't necessarily
controlled by the hypothalamus and this weight set point place, but just
everything else, whether it's emotions, it's people, it's all the food relationships that
these medications may also be helping. And in that way, it's really helping people treat this
disease of obesity. Yeah, the impact that the GLP-1 ones have on the brain is really remarkable.
I've heard story after story of people say it allows them to slow down and make much better decisions.
And in this way, it becomes really a tool for lifestyle change.
for lifestyle change. And in doing that, then, well, if you just look around and you see,
especially if you're in the United States, we're battling bad options all the time.
Everywhere, there's usually, it's pretty easy to access fast food or, yeah, so, yeah, there's a lot of antidotes online about how it's really a great
tool for making better choices. So, with that, I'm wondering, Dr. Chang, if you could give us
some insight into what is,
I guess some insight into the sex differences
that drive weight gain and also how
how weight changes across a woman's lifespan.
Absolutely.
So I think for women in particular, it's a challenging biology for researchers to
understand because we go through two or three major changes in our lifetime, right? We all go
through puberty, some of us get pregnant, and then we all go through menopause. And that is something that men just don't do.
And in fact, when you look at some of the research people do in mice, classically,
they have chosen to not study female mice because they were too complicated.
So if you imagine that, it's kind of crazy. How do we have all these medications
and what have you that have been studied in mice and then studied in humans and approved? And
the way they got started was just assuming that male mice were the same as female mice.
And now it makes sense how we assume that women are the same as
men and everything should be the same. It's mind boggling. But that's because of the complexity
of our hormonal systems and the phases of life that we go through. different set of stressors, I think, that can cause weight gain. I think
the biggest one for most of us is menopause related or just estrogen changes. Estrogen
changes all around, whether that's, you know, if you're dealing with irregular periods,
maybe a polycystic ovarian syndrome, or maybe you're one
of those people who have cravings right around your period, that's all estrogen related. And
that's because when they looked at estrogen in female mice, right, in female mice they studied,
when they looked at estrogen, they discovered that estrogen also acts in this area of the brain, the hypothalamus,
and estrogen actually acts to suppress appetite. So when we have a drop in estrogen every month,
right, when we have that drop in estrogen every month, which stimulates shedding of our uterine
lining and causing that period, we actually are losing one of the
signals, one of the hormones that suppresses our appetite. So if you think that maybe you're eating
a little bit more, or maybe you're craving a bit more, it's not in your head. It may very well be
hormonally driven by that lack of estrogen. And so when we look at menopause, that's the primary
problem. That's the primary issue in menopause is that we lose estrogen or we have these wild
fluctuations of estrogen going up and down, which is what causes hot flashes. But because of that
drop in estrogen, we also see a difference in our appetite and food relationships. A lot of
other things happen in menopause too. Hormone changes like insulin, for example, testosterone
may change a little bit, progesterone changes and decreases as well. And because of that,
we tend to lose some muscle mass. We tend to gain more fat, particularly around our truncal area, our abdomen,
and that predisposes us to other diseases like diabetes or high blood pressure or high cholesterol.
And because of all of that and the weight gain associated with it, I think the types of hormonal changes women have to deal with is slightly different from that of men.
And it means we really need more directed therapies that are specially studied in women and intended for our population use.
intended for our population use.
Yes, I've always wondered as a scientist why more researchers don't study women's biology
just from a scientific perspective. I mean, you have this fluctuation and change in hormones across the monthly cycle or over the lifespan. And
I've always thought that that should be more interesting to all researchers.
But I'm glad now that there are many more working in the space to understand the basic science behind menopause and perimenopause.
And yeah, so with that, I want to ask Dr. Chang about the study that you worked on with the SIRMount trials surmount trials and what you found looking at women who are taking trizepatide and across
perimenopause and menopause? Yeah, absolutely. So the surmount trials that you refer to
is the acronym for, I don't remember what it stands for, to be honest, because we often make
up these acronyms, but the surmount trials are those that tested terzepatide, also known as
ZEP-bound, for weight loss specifically, and it was looking in people with obesity or overweight.
And what I did with the manufacturer, Lily, was to re-examine that same data set, looking
specifically at women only, and kind of separating them out into different groups based on
reproductive stage.
So whether they were in pre-menopause, perimenopause, or post-menopause.
perimenopause or postmenopause. And the way we separated out the groups were very detailed,
actually. It was based on age, yes. Like if you were less than 45 years of old,
without any indications of menopause, you were premenopausal. If you were older than 55 years old, then you were definitively post-menopausal.
And we used a lot of other data points, hormones, reports of hot flashes or anything like that
to figure out if you were in that perimenopausal range or perimenopausal group. So we separated
them out into groups and then we looked at what was their
weight loss response to terzepatide. And our intention, our question was, does the reproductive
stage matter in response to terzepatide? Going into it, knowing the hormonal changes that happen
with menopause and the weight gain we see
with menopause, I would have guessed that being in menopause meant the trisopatide wouldn't be
as effective as if you were younger, you know? And I think we have somewhat of a lived experience
with this where it's easier to lose 10 pounds when you're 20. It's a lot harder to lose 10 pounds when
you're 50 years old. And so I went in with that hypothesis, which was proven wrong, actually.
What we found that regardless of whether you were in pre, peri, or post menopause,
the medication trisepatide worked well. It worked great, actually.
It caused that 15% weight loss, I think, or sorry, 20, sorry, 20% weight loss regardless
of what reproductive stage you were in.
And so that gave us, I guess, great reassurance really that this medication is effective a little bit,
regardless of what kind of hormonal issues
you're dealing with.
And it's something that we can use for any women,
any person in their lifetime, 18 or above,
this was only in adults, 18 or above,
to cause and to expect some weight loss response.
That's really encouraging.
And I'm wondering, and others might be wondering as well,
if, because we know with weight loss
and then also in the context of perimenopause and menopause,
there could be changes. Maybe you lose weight and it's not from fat, you're losing muscle. So wondering if there was any insight
from the research you did, if it was all fat loss or any concern for muscle loss there.
concern for muscle loss there? It's a great question. We didn't look at that specifically
because to look at body fat composition and body composition, there needs to be kind of more
advanced instruments, whether that's what they call a DEXA scan or a BIA bioelectric impedance analyzer. If any of you are members of higher end gyms,
those are machines where you hold on to a hand grip instrument or a special scale with
electrical platforms and it tests what your body body fat percentage is this particular study that
i was a part of didn't do that but looked at a measure that was a um a representative of fat
mass and specifically the concern that many women have which is the waist circumference so the amount
of fat that we carry around our waist. And that was
specifically captured in something that we call the waist to height ratio. So a waist to height
ratio is exactly what it sounds like. Actually, it is your waist circumference divided by your height.
divided by your height. And that waist circumference is perhaps a little bit
different than what we might think of in the fashion world. It's a little bit lower,
closer to where your belly button is and kind of where your belly might hang, as opposed to
the smallest part of your waist, which is where our fashion pants and skirts and dresses
really care about. But really examining where we're holding on to the majority of that weight
in that waist circumference and dividing that by our height. And that number, that ratio should ideally be less than 0.5.
So we should ideally be twice as tall as we are wide
is the kind of rough colloquialism to that.
And what they found, what we found in our analysis
of these surmount trials was that we were able to normalize that,
achieve that less than 0.5 ratio
in like 50% of our premenopausal women
and about a third of the women in peri
and postmenopause with terzepatide versus,
this is always compared to placebo,
which is really just lifestyle changes.
People who are just doing lifestyle changes,
almost no one achieved that waist to height ratio.
So we're really working with a different level of efficacy
here with these medications that is particularly targeted at that central weight issue.
That's really encouraging. And it seems like that suggests that there's,
it's more, I guess there's a debate if the GOP ones are just working through caloric restriction or if there's real changes happening to the metabolism.
So it seems like that suggests that there are real changes happening.
So that's really encouraging.
Yeah, it's a great question.
I think that for the most part, the medications right now,
semaglutide and terzepatide, particularly work through appetite suppression. So it reduces the
amount of food you're eating, and that's how it causes weight loss. There's some data suggesting
that perhaps there's a metabolic effect from the GIP component of terzepatide. So just to make that distinction, semaglutide is a GLP-1
drug alone. GLP-1 hormone is the only one that it affects. Terzepatide affects two hormones,
GLP-1 and this other one called glucose-dependent insulinotropic polypeptide.
We abbreviate that to GIP.
So GLP-1 and GIP are the two hormones that terzepatide affects.
And we think again from kind of mouse studies, and there was just a human study published
actually, that the GIP activity may have an effect on the level of our fat, where it improves the energy
use, the fat maybe is accessed better to be burned, we think. I'm waving my hands a lot here,
because it's hard to really define that, or to draw hard facts out of some of
our studies, but we think there may be a metabolic component to that. Now, future medications like
redditrutide, which is still in its phase three trials right now, so not yet FDA approved, may have further effects on that energy metabolism piece because
retrotreutide uses three hormones, GLP-1, GIP, and glucagon, which is the third. And then I think
that our next generation of weight loss medications will further push that envelope forward in the sense of looking really at
how can we get our fat to work better for us? Not just about eating less, but can we
get the fat stores that we have to really access them as energy sources? And this is looking at
different peripheral mechanisms, whether it's
the Magromab, which increases the amount of muscle mass, or Namasimab, which is a cannabinoid
one reverse, cannabinoid one receptor inverse agonist, that's CV1,
reverse inverse agonist, or medications that include glucagon like renotretide.
Yeah, I'm very excited to see where the space goes. It seems like it's moving very fast now. And I'll ask one more question and then open up to questions from the audience.
And if you're in the audience, you feel free to type your question or to invite or to request to speak.
But, yeah, so the last question I'll ask is around microdosing GLP-1s.
And maybe this is a controversial subject. So yeah, just wondering,
Dr. Chang, if you have any thoughts on microdosing GLP-1s. And I guess especially because once someone gets to their goal weight,
or if maybe they're looking for some of these effects on metabolism
and are less thinking about their weight,
if microdosing could come into play there?
Yeah, I think that's a great question.
And we don't have the answer to that. We haven't really studied microdosing on a large enough scale to have any
sort of FDA approval. I did just write an article for Medscape that I posted on my X feed, if you want to take a look at that, because the phase two trials in our research pipeline
always looks at different doses. They're called dose finding trials for a reason,
and they typically look at really low doses and really high doses to figure out
where do we find the dose range that gives us the best benefits with the fewest risks.
And then the doses that make it
through our phase three trials and make it to FDA approval are the ones that we see today on the
market, like the 2.5 milligrams, 5 milligrams of trisepatide, or the 0.25 up to 2.4 milligrams of
semaglutide. Those are the doses we see. But when you look at the phase two early trials,
doses we see. But when you look at the phase two early trials, you see other doses being used as
well. Typically, these trials are smaller, they're shorter, they're in very specific populations,
so we can't quite extrapolate it to apply to everyone. But it gives us a starting point
to understand, all right, what are the potential risks? Did it provide any benefit?
Was there any signals for or concerns for safety or anything of that sort? And so I, in my Medscape
article, I commented on a couple of these phase two studies that might help inform us on this
trend of microdosing. I do think that it needs so much more research, right? Because
people are doing it, whether we have the research or not. I think many times we think of the biotech
industry as the innovators, but it's really patients who are the innovators. I know you
guys are trying things because you know what your risk threshold is and you're doing your own research and gathering information from friends or the Internet or science, scientific papers and everywhere, really.
Hopefully, chat and AI nowadays to to figure out what makes sense for you. And I think it's really the responsibility of us scientists and the medical community
to capture that and understand that better so that we can provide evidence for its safety or efficacy or lack thereof.
or lack thereof.
Yeah, I think it's great for everyone to be aware of the safety data that is out there
because I know where I have heard the microdosing conversation the most is among those who use
those who use compounded GLP-1s.
compounded GLP-1s.
And if anyone in the audience is not aware,
you may get either a name brand GLP-1 like Ozempic, Manjaro, Zetbound,
and you get this either directly from the pharmaceutical company,
like Zetbound can be ordered directly from Eli Lilly with the
approval from your doctor, or you receive it at the pharmacy and it comes in, usually if it's at
the pharmacy, it comes in a pen that's already pre-dosed. If you order directly from Eli Lilly, this could come in a vial. And so that's
the name brand GLP-1s. Then there's also compounding pharmacies who will make doses of,
I guess, correct me if I'm wrong, but like generic semaglutide or trisepatide. And these come in vials. And so this microdosing conversation,
I've seen it come in when people are receiving the compounded GLP-1s. And there's many reasons
why they may go to compounded pharmacies because there's a big difference in the price as well. But yeah,
then I've seen conversations where people start to experiment with the doses there. But yeah,
I think it's super important to remember like what safety data is there. And as you mentioned,
Dr. Chang, that the microdosing has not been studied.
I completely agree with all of your points.
Yeah, so I want to invite you all again, if you have a question,
to come to the stage or to type your question below.
This has been a really great and insightful conversation.
And it's just really encouraging that there's a treatment that's already out on the market that women can potentially use for a number of different conditions.
So, yeah. for a number of different conditions.
So, yeah.
If there's no questions, I guess one quick thing to highlight is that there are, some people do experience, like, side effects with these medications.
It's not all, like, it's not always a simple solution.
There are like reported side effects of nausea,
extreme fatigue.
And so it's not always as simple as you take it
and it's a solution.
I think it's a long journey that you have to speak
to your care provider with every step of the way. And so with that, I want to just ask Dr.
Chang if you have any final thoughts of what you would like to share. Yeah, I think one final takeaway that's really important is that, you know,
we are all so different, even though we say that, okay, women are very complex, and they're different
from men, yes, but individually, all of our hormone profiles are different too, and so
that's why we need so much more research.
We need kind of personalized medicine. Whatever I say may be true from an evidence base and from
all of our research. But like you mentioned in the very beginning, Jenna, speak to your doctor.
They know you best. You know yourself best, because ultimately what we need is individualized
and personalized plans for everyone for whatever you're looking for, whether that's hormonal
balancing or weight loss or getting through menopause, fertility, what have you. And so I
appreciate the time that you gave us in the community and the time that I get to speak with Athena Dow.
Yes, thank you so much for joining us. And for everyone listening, please go read
Beverly's article. I've started following her tweets and there's a lot of great information
there. So please go read her articles and stay up
to date with the space.
And yeah, for AthenaDAO, we have some exciting things coming.
Our science and DILFO team has been working a lot on market research for wearable devices
and biosensors. So look out for more information regarding that.
Please join our community, our Discord. You can find the link in the link tree in the AthenaDAO
bio. And yeah, with that, thank you all for joining. And thank you so much, Dr. Chang,
for your insights. And yeah, we'll see you all next time.
Bye.
