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- [00:00]
A
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- [00:30]
B
you really have no idea what you are getting from a compounding pharmacy. There's been some data recently that showed that one GLP1 specifically when it is compounded with B12, which is a common practice at compounding pharmacies, another substance precipitates and we don't actually know if that something new is safe.
- [01:01]
A
Hi, Vanessa.
- [01:02]
C
Hi, Cara.
- [01:04]
A
Vanessa, we are recording this episode at an unusual time. We're doing it in your mid to late afternoon. Usually we do it in your morning. And do you know why? Well, do you know why I'm bringing this up at the top of the episode?
- [01:22]
C
No.
- [01:23]
A
Well, it's gonna have everything to do with the way our hormones work because right now would like to be curled up in a ball having a siesta.
- [01:37]
C
And in fact I did contemplate a 10 minute power nap before I was like, oh my God, we're recording at 4 in the afternoon. This is going to be dangerous.
- [01:47]
A
I bet you did. So we have with us one of our favorite people, one of our favorite doctors, endocrinologist Jillian Goddard. And we are going to Talk today about GLP1 receptor agonist, that hot topic. And we're going to do it in all different ways. We're going to talk about it with respect to kids, we're going to talk about it with respect to adults. We're going to talk about it with respect to health and illness and all the things. But before we get into that, I just want to tip my hat because Jillian has a new book coming out that's all about the ways that hormones circulate through the body and explains in one part in particular exactly why right now, Vanessa, you're like, where is my coffee? But also has a title that I think we just need to, we just need to share with everyone, which is the hormone loop. So welcome. We're so happy to have you.
- [02:50]
B
Thanks so much for having me back. I'm excited to be here.
- [02:54]
C
So, Jillian, we actually had a kind of a special thing happen which is that we had you on the podcast and hung out online in non Creepy ways. And then we actually got to have dinner together and we got to meet in person. That's a. There are very few guests who we actually get to then get to know in person. And we are very excited about having endocrinologists on, because you all make the really complicated and sometimes unknown parts of physiology and body changes feel a little more known. And yet, how many of you are there in this country? Not very many.
- [03:37]
B
No. There are actually fewer than 9,000 practicing endocrinologists in the United States, which calculates
- [03:45]
A
to, what, 1 per 19,000 or so?
- [03:49]
B
Yeah, I mean, there's 168 million women. We mostly see women, so it's about one of us to every 3,000 women. But we do. We do see men.
- [03:59]
C
So basically, there's not a lot of you and a lot of people to help. So when you came on the last time we talked, you know, about what is the endocrine system and specifically how it relates to puberty and menstruation. And so if people miss that episode, go back and listen to that, because it's really fascinating. But we're not going to retread that ground today, because we are going to cover a topic which a lot of people may not even realize is related to endocrinology and to your expertise, and that is GLP1s, which is like, if you're like me or many other people, it's all over your Instagram feed, It's all over your email blast. It's on the tip of everyone's tongue everywhere you go. And yet there's so much we don't as lay people. I'm speaking for myself. We don't actually know or understand about them.
- [04:58]
A
Even doctors. There's a lot we don't understand and know about them. Vanessa, really?
- [05:03]
C
Right. I mean, I. I trust Jillian is gonna.
- [05:06]
A
Well, she's the doctor on the podcast who does know about them. So there we go.
- [05:11]
C
And, Kara, usually you know a lot about subjects, even if it's not your expertise, but in this case, it's complex. It's new. It's sort of emerging as we. As we speak. I want to approach this conversation in a way that we do all other conversations, which is about the science and understanding the science, admitting what we don't yet know in the science, thinking about it for us as adults, as Carr mentioned, also thinking about it in relationship to children, and then thinking about how it affects our social, emotional reality, our cultural reality, all of those things which, you know, I know that's not your expertise as an endocrinologist but you're experiencing it firsthand. You saw 16 patients today. I'm sure some large percentage of them are thinking about or currently taking GLP1. And you engage with them as whole human beings. So we probably won't get to a lot of that today. But in terms of acknowledging that this is not just a medical conversation, but a whole human being and a whole society, conversation is an important part of going on this journey together, a hundred percent.
- [06:21]
B
I mean, one of the big things that I talk to my patients about is how much this is a, a medication that is so much bigger than just weight loss. And that's actually always where I start when we, when we're having this conversation.
- [06:39]
C
So walk us through what are GLP1s? Because for some reason it's just Ozempic has become the sort of like Tampax, like the like brand name of them, but they're not actually all the same and they weren't initially created for weight loss. So just talk us through the sort of the origin story and the purpose for which they were initially created.
- [07:04]
B
Absolutely. So a GLP one is actually a hormone that we make in our bodies. It's glucagon, like peptide one, and it is made in the cells of our small intestines in response to carbohydrates. So we eat carbohydrates and the cells in our gut make GLP1. When we first discovered GLP1, which was not until the 1980s, we thought that all it did was go to the pancreas and tell the pancreas to make insulin. And right off the bat when it was discovered, scientists were really interested in using it to treat type 2 diabetes. Where we want the pancreas to make more insulin. The challenge There is the GLP one our bodies make lasts for minutes, roughly 6ish minutes in our circulation. And something that only lasts for six minutes isn't a super useful drug. So in the 90s, some scientists working at the VA hospital in the Bronx actually discovered that Gila monsters, which are these lovely lizards from my native neck of the woods, Arizona, they make a similar hormone in their venom and they were able to isolate this hormone, Exendin, and they made the first GLP1, which was exenatide. And that drug was actually approved to treat type 2 diabetes by the FDA all the way back in 2004. The reason GLP1s weren't on people's radar sooner is because the early GLP1s were frequent injections. Exenatide had to be injected Twice a day. And they actually didn't result in a ton of weight loss, although doctors were interested in this possibility even, you know, 20 plus years ago.
- [09:01]
A
So what changed?
- [09:02]
B
A couple of things changed. We iterated on a theme. So we went from a drug that needed to be injected twice a day to a drug that needed to be injected once a day to a drug that needed to be injected once a week. The companies making these drugs realized that doctors were interested in potentially using them as weight loss medicines. And so they started, started doing those clinical trials. And actually liraglutide, which is a once a day injection and was the second GLP one, was approved for weight loss all the way back in 2014, but it was a daily injection and it was, it was effective, but it wasn't amazingly effective. And so it was a little bit of a tough sell, honestly.
- [09:45]
C
Right.
- [09:45]
A
And, and I think it bears mentioning that as these drugs are being developed and coming to market, the average weight of the average American is going up and up and up. So there were sort of two lines moving in two directions. Right. And the in business it's, you know, your total addressable market is just, is growing the number of people who might need this medicine. I have to imagine in 2014 it was a significantly larger group than it was back in 2004 when the first iteration showed up.
- [10:19]
B
Yeah. And I think that the other thing that has happened in those intervening, you know, two decades is the idea that we should be approaching chronic illness proactively. We are in the midst of a shift from a very reactive approach to chronic medical problems to a more proactive approach. And that was something that was really still developing even when liraglutide was first approved for weight loss, you know, more than 10 years ago.
- [10:51]
C
For the layperson, can you put a finer point on the relationship between chronic illness like type 2 diabetes and carrying extra weight? Our audience has heard a lot about the relationship between earlier onset of puberty and girls and carrying extra weight, but we haven't explored this later in life phenomenon.
- [11:14]
B
Yeah, I mean, I think that it's a really complex relationship that we really have barely scratched the surface on the relationship between weight and chronic illness. The old model was this idea that you gained weight and gaining weight caused the chronic illness. We now think that it's much more complex than that. Probably there's genetic predisposition for both the weight gain and the chronic illnesses and that it's not such a causal relationship between weight and chronic illness and the chronic illnesses we're talking about to be clear. Type 2 diabetes, high cholesterol, heart disease are really important diseases because they're the ones that, that most people die from ultimately.
- [12:07]
A
And again, you know, just to make sure we're broadening the lens because it deserves to be broad. Vanessa, these used to be adult diagnoses and they're not anymore. So we used to think of these things as showing up later and later in life. And Jillian, do you want to walk through that piece of it a little bit?
- [12:28]
B
Sure. I think that there are things that happen to us in midlife, particularly women, but, but men to some degree too. Changes in our reproductive hormones that make us particularly vulnerable to metabolic disease in midlife and beyond. A hundred percent. But one of the things that's been happening in increasing numbers in the last, you know, several decades is that we are seeing more and more kids. They're developing overweight, they're developing obesity, pre diabetes and even diabetes, type 2 diabetes in, in adolescence, high cholesterol. Things that we really used to only see in midlife, we are starting to see now in adolescents in particular.
- [13:22]
A
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C
Canva, the thing that makes makes anything a thing. And is it still considered as complex and not necessarily causal a relationship as you were talking about in adults? Is it clearer in children? How, how do we understand that?
- [16:19]
B
This is a great question. I think it's just as complex in kids. For a long time we really blamed the kids and their families for developing overweight and obesity. And now we really realize that the drivers that cause certain people to gain weight, certain people's bodies to respond to things like sugar and starchy snacks, there's a huge genetic component to that. It's hard to pick apart because most of us are, are raised by people with whom we share genes. And so picking apart the relationship between our genetics and our environment, you know, this, this is a question that researchers have struggled with for time immemorial. But the more we understand this and the more we see that this is changing as our environment is changing, I think it points to more complex and
- [17:20]
A
that's a huge little side comment that deserves its moment. Our environment changing. I mean, you know, just look at how our lifestyle and our food choices and the ingredients that go into our foods have shifted. This is, you know, I, I want to be really careful that this topic has been politicized. This is not a political topic. This is, there is no politics to this at all. There have been researchers looking at this for decades. And what we have known for a very long time is when you put a ton of sugar into your shelf, stable foods that are cheap and easy for people to grab on the go, what you see are a lot of these metabolic impacts. Right, Jillian? I mean, this is not this isn't political. It's just. It just is.
- [18:13]
C
Right. But it is political because these cheap foods are for families who. Where parents are working two and three jobs and have like our.
- [18:24]
A
That is right.
- [18:25]
C
Like in their. Facing systemic racism and they are under chronic stress and they and their children have experienced adverse childhood experiences, which causes them maybe to have all sorts of mental health reasons, which is maybe why they're. It's like. It is so political.
- [18:41]
A
It is. I guess what I meant is I just don't want to put any kind of maha stamp on it in one direction or another, because this is not about, you know, the ultra process, anti ultra processed movement. When there's science that shows that when you have an ultra processed food with sugar in it, it is problematic for anybody that ingests it. And that in and of itself, that little narrow I. Oh, the big tent you just threw up, Vanessa, is not just 100% political, but you're 100% right about that.
- [19:15]
C
So, listeners, you can hear that even though we're talking about, you know, a hormone and a drug that was created to act like that hormone. It is actually a massive, complex issue where we're thinking about the entire health of a nation in relationship to this very specific corner of a conversation. And you've heard our conversations about all sorts of related topics, so we're gonna dive in. Jillian, I would love for you, because you talked about diabetes, I just would love for you to explain to our listeners the difference between type 1 and type 2 diabetes, particularly as Cara mentioned, the earlier onset of it, type 2 in children, which is its own set of, you know, of. Of worries and complications.
- [20:04]
B
Yeah. So this is a huge confusion for people, and it's partly because of names that we've used in the past. But I think the easiest way to think about it is type 1 diabetes is an autoimmune disorder where the immune system attacks the insulin producing cells in the pancreas. So the pancreas can no longer make insulin. It most often is diagnosed between the ages of 10 and 20, so during the adolescent years. But it can really be diagnosed anytime from the age of about six months all the way up to. I once diagnosed a woman in her 70s. We used to call it juvenile diabetes, a huge misnomer. But it is. It is an autoimmune disorder and the body cannot make insulin.
- [20:57]
A
And there's a lot of evidence that points to a viral trigger. Will you explain that, Gillian?
- [21:03]
B
Yeah, there's a ton of evidence that what happens is the kid has a genetic predisposition to form a particular immune response to a virus. It can be a number of different viruses that, that can do this. The kid then gets the virus as kids do, and when they get that virus, their immune system starts making antibodies that then can attack the pancreas and those insulin producing cells in the pancreas. So it's both genetic and triggered by the virus.
- [21:43]
C
Okay. And then type 2, by contrast, type
- [21:46]
B
2 is completely different. We have always said that type 2 diabetes was a lifestyle disease, but in fact, the biggest factor that determines whether or not you will get type 2 diabetes is your genetic. And so I think that's really important to state. Just because you have a good lifestyle does not mean you're out of the woods if you've got lots of family members with type 2 diabetes. Type 2 diabetes, though, is actually a process that occurs over the course of decades. Where originally what happens is your body stops responding well to insulin, and so your pancreas has to start making more insulin. And that can happen decades before people know that it is happening. Over the next several decades, your pancreas keeps having to churn out more and more and more insulin to keep your blood sugars normal. Eventually, the pancreas starts to tire out and the blood sugars start to creep up. That's what we call pre diabetes. And then the pancreas gets even more overwhelmed by the insulin resistance and the blood sugars really start to go up. And at a certain threshold, we call that type 2 diabetes. So even though we talk about insulin in both type 1 diabetes and type 2 diabetes, type 1 diabetes is really a disease of insulin deficiency. Type 2 diabetes, there's actually tons of insulin around. The body just can't respond well to it.
- [23:27]
C
I mean, one would think maybe they should have just called them two different diseases.
- [23:32]
A
One would think.
- [23:33]
B
One would think, yeah, if if only
- [23:35]
A
you had been there during the naming,
- [23:37]
C
Vanessa, it would be so good at the branding.
- [23:39]
A
You know, I. I will say, just on a personal note, that that comment about the genetics behind type 2, there are lots of people who carry excess body weight who will never develop type 2 diabetes, and there are people who are skinny mini bean poles who do develop type 2 diabetes. And I think that that is sort of a visible reminder to all of us that there's not a phenotype, so to speak. Right. And I don't know if there's anything more to be said said about that other than it's subtler than it might look. Right.
- [24:20]
B
100%. If you have a parent with type 2 diabetes, this is something you need to be concerned about. If you have two parents with type 2 diabetes, your risk of developing type 2 diabetes is about 70%.
- [24:35]
C
Yeah, I mean, my kids have. Our entire family tree is filled with. On both sides of my kids family tree is filled with people with type 2 diabetes. So it's something I like to talk to them about and they occasionally listen to me about. So I want to talk a little bit about the amazing stage of life that we're all in and many of our listeners are in, which is some version of, you know, perimenopause, menopause, post menopause. And I'm not going to go through it all because you do it beautifully in the book. And I want to people to, to read the book, but I do want to talk specifically about the joy of your body changing during this stage of life to the point where you're, you need an entirely new wardrobe. And you don't, you're like, oh, when did that part? A new lump and bump arrive in new places? So what happens in midlife? I'll call it midlife because I think men, and I'll ask you if men have a experience, some sort of parallel experience. Does menopause cause us to gain weight? Is there some other metabolic situation that's causing this joyful experience? Like, what's the, what's the story?
- [25:52]
B
Yeah, so women really do gain weight during perimenopause and menopause. It's a little tricky to tease out whether it's aging versus hormones. But we do know that estrogen keeps us storing fat in our hips and thighs. And when our estrogen levels fall during perimenopause and menopause, that allows us to form fat in our midsection. And that fat in our midsection metabolically makes us insulin resistant. Once you become insulin resistant, you make more insulin. That insulin tells your body to store the carbs that you consume as fat in your midsection, which makes you more insulin resistant, and you just keep feeding forward. The other thing that happens in midlife is women lose a small but sort of important amount of muscle mass. It's really only about a pound on average over the entire menopausal transition. But that pound of muscle, muscle is very metabolically active even when we're at rest. Fat is not very metabolically active even when we're exercising. And so when we swap out a pound of muscle for a pound of fat, we burn fewer calories. And so if we're burning fewer calories, but we're actually consuming the same Number of calories. The math tells us that our weight will increase. And so there are a couple different reasons why this happens. There's also some complexities that we're just starting to understand about how follicle stimulating hormone, which is the hormone in our pituitary gland that tells our ovaries to make estrogen. This hormone goes up exponentially in perimenopause and menopause. And we are just starting to understand that FSH probably has receptors in other parts of our bodies, not just in our ovaries. And we know that we have FSH receptors in our adrenal glands, which is where we make cortisol, which is where we make testosterone. And so we don't totally understand exactly what FSH is doing there, but it's pretty clear that. That it is having effects through the adrenal gland on our metabolic function. It may be causing high blood pressure and more insulin resistance.
- [28:26]
A
And men have pituitary glands that make fsh, and men have adrenal glands that make, you know, all the adrenal hormones. So have we studied them yet to see if that's what explains what is happening? I mean, I don't even know how to quantify what is happening to them in midlife other than to say something is happening to men in. In midlife. And is. Do you think there's. There's something there?
- [28:49]
B
Well, you know, men are a little bit different in that their testosterone levels do fall over the course of their lives. They do not fall dramatically in midlife the way women's estrogen levels fall dramatically during midlife, but they do gradually tick down from 45 or 50 onward. What doesn't happen with men that happens with women is, is this rise in fsh, in follicle stimulating hormone that. And women do have that. However, when testosterone levels drop, that does affect men's muscle mass. And men naturally gain weight in their midsections throughout their lives because they don't have so much estrogen. And so the causes are probably slightly different, but the effects are largely the same.
- [29:40]
A
Okay, can we wind back to one little passing comment you made about metabolism? I would just love to drill down for a second and understand, because there's the math equation of calories and calories out. But then there's what we were talking about earlier, which is the quality of what you're eating. And, you know, maybe it's caloric density. There's more calorie packed into every bite.
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B
But.
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A
But often you can have two foods with. If their ingredient lists had a calorie count, the calorie count would be the same, but the impact on the body is so different. Should we be throwing out this concept of calorie and looking at our metabolism differently here?
- [30:26]
B
I think we have to kind of use both. So yes, in a perfect world, we can measure how much energy we are burning at rest, at exercise. We have ways to do it. And they're, they're pretty accurate in most cases. And so if you're healthy and humming along and eating pretty healthfully, a lot of times the calories in versus calories out equation does work. But if you are starting to develop insulin resistance, a lot of times the math goes right out the window. And I see, I see this in my office every single day. I see women who come in who've been told by other medical professionals that they must be consuming some crazy number of calories to be seeing what they're seeing with regard to their weight. And in fact, when we dig a little deeper, they're pre diabetic, their insulin levels are through the roof. And when we manage those things, often without really substantially changing their caloric intake or output, they're able to lose weight. And so insulin is this other piece that modifies what our body does with the calories we consume. And what it wants to do is store all those calories as fat for later.
- [31:52]
A
And can I just add, Vanessa's going to. I want you to ask Vanessa because you've been very patient with me, but I want to get to at some point then how we circle back to GLP1s in this population who maybe the outside forces aren't shifting that much. What they're putting into their body isn't shifting that much. Their exercise isn't shifting that much, but their bodies are changing and the way their bodies are shaped is changing. So I want to sort of get there, but Vanessa, I'll back off until we get there.
- [32:19]
C
Let's go there. I just want to put a point on my question about. It's a little bit complicated. So I'm going to ask it and then you tell me if you actually want to answer it, Jillian, which is that higher rates of FSH as the ovaries are working harder to produce whatever, if any viable eggs are left in the ovaries, which also then is produced in the adrenal glands, where listeners, you may remember, is also where cortisol is produced, the stress hormone. Do we have any understanding of the relationship between that interaction and the shitstorm that we're all experiencing as middle aged perimenopausal menopausal, women. Like, do we have any, any knowledge about that?
- [33:06]
B
Not nearly enough. This idea that we should be looking at FSH and FSH's effects in the adrenal glands is a relatively new one. It makes sense because women experience a lot more. You know, we've all experienced, I was going to say irritability, but rage is a great word too. Yeah. Irritability, depression, anxiety are all things that come up in the perimenopausal years. And they're very organic. It's not just that we've got adolescent kids and aging parents. It's that there's something biochemical going on. But I will tell you mean, you'll both be shocked to hear that this really hasn't been well studied up to this point.
- [33:52]
C
But they spend so much time and money studying women and our health. I can't believe this is the last corner of our health that hasn't been examined. Okay, so Jillian, you'll come back and, and, and talk to us in 20
- [34:05]
A
years when someone studies it seriously.
- [34:08]
C
So let's get to Cara's question because, and I just want people to know we did, we didn't meander as we normally do through all these many questions and then sort of inadvertently end up here. There's a reason why we lay the groundwork with all of this background and all of these questions, because this is not a casual subject. This is an important subject. And with a medical professional who sees people over and over, all of these questions get taken into account. As we now expect explore the question of GLP1s. Jillian is meeting people who come in with this probably the same complaint over and over. And she's now going to understand the entire context of the conversation before she gets to this part of the conversation.
- [34:54]
A
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- [35:58]
C
So you want to give us a scenario, Dylan? You want to give us a, a hypothetical patient who comes in, who then you reach the point where you're like, okay, let's have a conversation about GLP wants.
- [36:10]
B
Sure. Let me tell you about a patient who I met her when she was in her early 40s, rapidly had three kids in quick succession. Her last kid was born in September of 2019 and she had a baby, started a new job and works in a very public facing job and then had to learn how to do that very public facing job through the pandemic. And in each of her three pregnancies she had had gestational diabetes. She had worked very, very, very, very hard to manage her diabetes during her pregnancies just with diet. She never needed insulin. And after her last pregnancy her blood sugars were normal and she went into the pandemic and did all these things. And I met her a couple of years later and she came into my office. Her average blood sugar was in the pre diabetic range. It was not super far from diabetes. She was, you know, 42 or 43 and she had little kids at home. She weighed more than she had weighed when her third child was born. I saw her in September and she had spent the month of August, which included her own birthday and a vacation, doing the whole 30 and exercising five days a week. She didn't even have a glass of wine or a piece of cake on her own birthday and she lost two pounds. And she was a really concerned about her health. She had high cholesterol, high blood pressure and high blood sugar. She's got these three little kids at home and she's totally frustrated because if you think about it, why would you keep eating the super healthy diet and, and really being so strict for zero benefit? It, it makes total sense that people then give up and go back to what they were doing before.
- [38:11]
A
I feel like I know where the answer is going to.
- [38:13]
B
Yeah. And so we had a whole conversation about her and her health and how to think globally about her health problems. And together we came to the conclusion that she needed to do something to manage her blood sugar. And we talked about a few different options and eventually we settled on a GLP1. How often she's doing great now, by the way.
- [38:40]
C
That was great. How often do you, when you have these kinds of conversations, do you hear about the shame or the embarrassment or the desire for secrecy about, you know, needing to take these medications?
- [38:57]
B
Often I mean I have a lot of patients who are very high achieving, getting it done. Women, they've got kids, they've got jobs, they've got other family members, they're doing a lot of things and they're able to accomplish all these things. And their health and managing their health is the one thing that feels unmanageable.
- [39:27]
A
So I want to talk about that exact same scenario. But if it's a teenager, I mean, not with the three babies as a teenager probably and the public facing job. But, but you know, being a high
- [39:42]
C
school student's a pretty public facing.
- [39:44]
A
It is pretty public facing, let's be honest. But you know, how does your advice change by age, demographic and you know, what, what is the FDA approval limit for these drugs? And then as someone who prescribes them and who's comfortable using them and by the way, not all doctors who who have the ability to prescribe drugs are or should be comfortable using them. You, you know, it really, when you choose your doctors, choose doctors who have expertise connected with the drugs they're going to be giving because those are the people you want to manage the drugs. Just a little side PSA there. How does your advice change? If they walk in and they're, I'm going to give you three ages 22, 17, 13.
- [40:34]
B
Let's start with the FDA approval that's important for a number of different reasons. Semaglutide, which is Ozempic and Wegovy, is approved for the management of overweight and obesity in children ages 12 and up. And it is approved for the treatment of type 2 diabetes in children ages 8. Enough. And that's a zo. So that matters for a couple of different reasons. One is that's what we have literature on. That's what, where we have data collected in randomized trials. So that is important to me. But the other reason that it's important is because these drugs are quite expensive and if they're not within the FDA approved uses, your insurance will not pay for them. And so I think that's an important practicality as well.
- [41:24]
A
Can you do a quick side journey, just a couple of sentences on why cheap is expensive with these drugs and you must buy them from a pharmacist. Yes.
- [41:36]
B
So when you buy them from a pharmacist, they are coming from a factory that is regulated by the fda. The FDA goes in, they actually monitor and make sure that you're getting what you think you're getting and they make sure that the amount of are correct. When you get these medications from a Compounding pharmacy. None of those things happen. Compounding pharmacies are not regulated by the fda. They're actually regulated at the state level. There's a lot of variability, and you really have no idea what you are getting from a compounding pharmacy. Add to that that there's been some data recently that showed that one GLP1, specifically tirzepatide, which is Mounjaro and Zeppbound, when it is compounded with B12, which is a common practice at compounding pharmacies, another substance precipitates, so, meaning the chemicals combine and make something new. And we don't actually know if that something new is safe. And so I really encourage my patients to get off the shelf pharmaceutical products from a pharmacy.
- [42:46]
C
So, Jillian, you threw out a bunch of names, and there's different names for whether it's being used for to treat type 2 diabetes versus obesity or weight loss. And they sort of sit in two separate camps. Can you help people understand what the difference is and how are they different medications even or working on the body?
- [43:09]
A
And then we'll circle back to the kids because I think people want to know kind of what to expect from their care provider. So let's do all of that in one giant, giant lump.
- [43:19]
C
Okay.
- [43:20]
B
So when we talk about these medicines, we're really at this point mostly talking about two different molecules, semaglutide and tirzepatide. Semaglutide is marketed as ozempic for type 2 diabetes and as Wegovy for overweight and obesity. Tirzepatide is marketed as mounjaro for type 2 diabetes and it's marketed as Zepbound for overweight and obesity. Semaglutide is a GLP1 receptor agonist. It acts specifically on the GLP1 receptors throughout the body and acts like the hormone GLP1. So it turns on the receptor. Essentially, Tirzepatide is also a GLP1 receptor agonist, but it also acts on a second receptor called gip. And that second receptor is also present throughout the body. And we think, although we do not know that it is the GIP receptor, that is the reason that tirzepatide seems to result in more absolute weight loss than semaglutide.
- [44:45]
C
And then there's a third that I've been hearing about from my teenage sons, which is. Has a third component, retatrutide.
- [44:53]
B
Yeah. So retatrutide is a triple agonist. So it. It's GL, the GLP1 receptor. It hits the GIP receptor and it Also hits the glucagon receptor. So glucagon is sort of like the opposite of insulin. Insulin helps the cells take up sugar. Glucagon helps the cells release stored sugar.
- [45:19]
C
Yeah. So the. Let's talk about men and retatruchide and why teenage boys are hearing so much about it.
- [45:25]
B
So why teenage boys are hearing so much about it is because we think it may affect muscle less and so you may see less loss of muscle fat. Although I think that there's some really important details about the muscle loss we see with these medications. However, retatrutide is not yet approved by the fda. So if somebody's taking retatrutide, they are getting it from a compounding pharmacy. And it's not the previous comment.
- [45:54]
C
Yes.
- [45:55]
A
And, and then do you see any differences in the brain effects of any of these classes of drugs or these types of drugs within this class? Because of course we've all heard about the quieting of noise when people are on, frankly all of them.
- [46:15]
B
I think that some of the differences in how these two drugs, semaglutide and tirzepatide specifically affect our body actually probably, and we don't have all the data on this yet, there's a lot we don't know about how these drugs are acting on receptors in different body tissues. But probably the difference has more to do with how similar they are to the body's own GLP one and less to do with which receptors it's hitting. So to give you some sense, these are all peptides, it's just a string of amino acids. Liraglutide, which is that Once daily old GLP1, it's only one amino acid different from the GLP1 our body makes. Semaglutide is about 85ish percent the same as the GLP1 our body makes. Tirzabatide is actually only 50 to 55% the same as the GLP1 Our body makes. That may explain some of the differences that we are seeing in clinical trials around the non weight loss effects that people experience with these medications.
- [47:36]
C
And before we get to teens, can you speak to the relationship between these medications and addiction? It substitutes substance use and what we know or don't know. Or is it just sort of like observational at this point?
- [47:51]
B
No, there are some studies, some actual clinical studies that have come out around addiction. There was a big study that came out of the VA hospital, the VA hospital system that looked at patients with different types of substance use and they did see a difference in relapse in patients taking GLP1s. That study looked at all different GLP1s. And so we're just starting to get the beginnings of those clinical trials looking at different types of addiction and how GLP1s are affecting that addiction. We know that GLP1 crosses the blood brain barrier. We know there are GLP1 receptors in the brain. We think that there are some modulating effects specifically on dopamine in the brain and the way dopamine works in the brain. And in fact, in addition to addiction, they're also looking at how these drugs might affect attention and attention in people with adhd. So we think that it's related to dopamine. We're really just starting to think about these pathways critically, but we are starting to get some data.
- [49:06]
C
And Jillian, as we move into the conversation about growing children, do you have concerns about what we do not yet know and these medications?
- [49:19]
B
I think any time you are considering starting a medication, and this goes for teens and for adults, you really have to weigh the potential benefits with the potential downsides, including the possibility that we will learn about downsides in the future. I think that this can understandably become more fraught when we're talking about teens, because we're making decisions in some ways for someone else and typically for some of the people who are like the people we care about and want to do the best for more than anyone else in the world. I mean, we're talking about our kids. And so I do think that that makes the decision more challenging because we're not making it for ourselves, we're making it for our kids.
- [50:17]
A
Right. And there's a really solid story that sounds like these drugs are a total panacea. They fix. I mean, I've read articles in really respected medical journals that are like, they fix everything. And I don't think that's without merit. It's just that you're sitting there. Now let's go to our case. Our 2217, 13 year old. And there's this thing that weighs on me as the pediatrician, which is like, you want to treat the issue at hand. And this is an issue, and an issue that we've established over the course of the past hour is not entirely about lifestyle choices. It is largely genetic, but it is also driven by lifestyle choices. And those choices are hard. It is not like, you know, the cost of a salad and the cost of a burger are the same.
- [51:13]
C
Same.
- [51:14]
A
And the ease and the grabability and the flavor and all those things.
- [51:19]
B
And the peer pressure.
- [51:20]
A
And the peer pressure. And so you're sitting here and you're like, if I treat this issue, which is not entirely within anyone's control, but especially with someone whose limbic system is dominating their brain and their prefrontal cortex is not fully developed, if I treat this issue with a panacea medicine, am I not helping them solve the bigger lifestyle questions down the road? Which feels like a very judgy approach to the whole thing. So I only say it insofar as I get where when people say that, I get all of it. And I think all three of us do. Like, we understand the necessity, we understand the benefits, we understand the downsides, we understand all of the downward forces on these kids. So you got a 22 year old who walks in, who fits the scenario of clearly could benefit from one of these drugs with all the other, asterisks aside, don't know how long they're going to have to be on it, maybe the rest of their life. And the question is, what do you do at 22, what do you do at 17, what do you do at 13? And what do you tell them they need to not also put into their body when you are on these drugs?
- [52:35]
B
I think 22 and 13 are actually the easiest.
- [52:39]
A
Hmm.
- [52:39]
C
Oh, fascinating. Not the answer I was expecting.
- [52:42]
B
Okay, so let's start with 13 because I think that is where the most caution makes sense. I think particularly in a kid who is maybe not fully developed. I think particularly in a kid who is, you know, peripubescent, which you may be at 13, especially a boy, but girls can be too. You need a really compelling case. You need a kid who's pre diabetic or diabetic. You need a kid who has terrible lipids. In my opinion, you need a kid who has, and I hate BMI as a metric, but in this case you need a kid who's off the charts bmi. And it's very clear that it's been something that's been going on for a while because young bodies are pretty resilient. A lot is shifting and changing in puberty. And I think that that is the kid that where I exercise by far the most caution. I would never consider a GLP one in a kid this age without an endocrine consultation.
- [54:01]
A
And I'm going to guess you would multiply that by a hundred for an eight or nine year old.
- [54:06]
B
Yes.
- [54:07]
A
Okay.
- [54:07]
C
Yeah.
- [54:07]
A
So just establish the baseline.
- [54:10]
B
Okay. Yeah. I mean, this is where you need an experienced pediatric endocrinologist who understands how blood sugar and weight gain and hormone levels, reproductive hormone Levels and growth are all interacting with one another. The 22 year old tends to be one of two things. It's a kid who's struggled with weight their whole life and it's really limiting them. And they are starting to have some metabolic issues related to it. They've often done some things on their own. A lot of times in young women, we're talking about a young woman with polycystic ovary syndrome, where we know what's happening from a hormonal point of view is really causing problems. And here I feel like I can have a conversation with a 22 year old about, well, this is what the long term looks like. These are the pros and cons. This is the type of diet that you need to have in place. This is, you know, this is what has to happen in order for this to work for you and in order for this medicine to make sense. I think the 17 year old is the hardest for a couple of different reasons. One is virtually all girls and the vast majority of boys will be through puberty. They will be fully developed from a hormonal point of view. Maybe not from a brain myelination, prefrontal point of view, but from a hormonal point of view. These kids are almost always fully developed. They're also still living at home most of the time. And they're also about to not be living at home in many cases. And in many cases, they're about to go through a transition that is difficult from a nutritional point of view, regardless of whether they have weight issues or not. The transition from home to college, to eating in a dining hall, to drinking, that is really challenging. And so this is where I think we need a lot of nuance around how mature is the kid really? What have they really done thus far to try to improve their lifestyle? Are they eating one thing at home and then going out with their friends and eating total crap? Probably. I'm pretty sure that's what my kids do who are in this age group. And so I think you gotta like dig in with the individual kid here. And I do, I have some patients who are very mature who again, oftentimes young women with polycystic ovary syndrome, which does involve insulin resistance, who come and are very aware of the downsides, they're very aware of what they're supposed to be doing, and they're very engaged with the dietitian. I insist that this age group works with a registered dietitian, insist that they work with a registered dietitian as they transition to college or out of the house. If they're willing to engage in all of that, and they are, they're mature in their reasoning and thinking, I think it can be a great option.
- [57:28]
A
When we put them on birth control pills, we say to kids, you cannot smoke because of the risk of blood clots. Is there any word of warning you give kids, especially that 17, 18 year old group who's heading out of the house. But frankly, any tween or teen, from
- [57:47]
B
an alcohol perspective, I tell them the same things I tell other kids, which is you should not be binge drinking. I also try to be cognizant of the fact that that may be going straight in one ear and out the other. But the one positive thing about these medicines in this age group is that you will know if they are doing things they're not supposed to be doing because it will make them really sick. So the things that make people sick makes gastrointestinal side effects worse, are eating lots of super simple carbohydrates, which is something I tell people not to do always, but particularly when they're taking these medications, eating really fatty fried food. So like bar food, you know, the fried mozzarella sticks and the chicken wings and alcohol. And so if I've got a kid who's coming to me and constantly complaining about how sick they are, this is an area where the dietitian and I will dive into, well, are you eating the simple carbohydrates? Are you drinking too much? And kind of dig into some problem solving. But that's the one good thing is it does, it does keep them honest.
- [59:03]
C
Gillian, can you talk about the larger messaging when you have these conversations with kids? Right. They're coming in maybe with a parent, maybe not with a parent. Someone's concerned. They're both concerned. And you're thinking about sort of lifelong health. And that's not just physical health, that's mental health and self esteem and all of that stuff. How do you talk about weight loss and how do you talk about health without sort of like throwing out all the work that we've all done for decades around body positivity at the best, at least body neutrality. How do you balance that?
- [59:45]
B
This is not a question that's just germane to teenagers, by the way.
- [59:49]
C
Right, right.
- [59:50]
B
I have these same conversations with women at midlife all the time. So the first thing I do, and I do this in every conversation I have, I really shift the conversation away from the number on the scale. I tell people right off the bat that I think body mass index is a terrible metric, and we won't be using it for anything other than the insurance company who requires it. I do not use it in setting goals. I don't actually use weight in setting goals. I actually completely try to get take the scale out of the conversation and get really focused on all the other things that we're hoping to accomplish. So getting back to those other metrics, the blood sugar, the cholesterol, the blood pressure, I mean, if you've got a kid who's already got high blood pressure, that is something you can A, impact and B, one of the beauties of weight loss is that gets better really, really quickly. But the other thing I really focus on is how they want to feel, physically feel in their bodies. And I don't mean, like, what they want to look at looks and see in the mirror. I don't mean that they want to get on a particular dress. I mean, like, what do you physically want to be able to do that you cannot do right now? And I think when you shift away from weight and toward ability and feeling strong and feeling healthy, that's sort of an important shift to make. I will also tell you that, you know, I don't think that a kid who's struggling with disordered eating is necessarily like, I don't think that that's necessarily I an I won't go there situation. Because while certainly there are psychosocial aspects to disordered eating, there's also biochemical aspects to disordered eating that are often related to all these same things, insulin and blood sugar, and how the body is processing those things. And I've seen kids who are really struggling with binging, for example, is a common one, because they're desperately trying to lose weight. They're restricting, restricting, restricting until they can't take it anymore. And because they're fighting their own brain and then they binge. And so, yes, you have to be very cautious, but I do think that there's potentially some benefit there, too.
- [62:30]
A
It's such an interesting place to land because I think we, you know, Vanessa and I talk about this on other podcasts. We talk about this in our curriculum, how disordered eating and eating disorders that travel with carrying extra weight are so often missed. And it is so important that we are looking at healthcare solutions for all people, regardless of what they're struggling with. Even if the way they look does not match in your mind the way you think they're supposed to look, there are lots of eating disorders that are really deeply connected to carrying too much body weight. And that piece of it, when solved and treated with people who are professionals and have experience in the area. You nutritionists, therapists, psychiatrists, right. That when you address one piece of it, all the other puzzle pieces have permission to fall into place. And it's not to say that this is an easy fix, but it's just such a fascinating place to land because I think we're gonna find another hundred applications for this class of drugs over the next very short while. We're also going to hear some bad stories. We're going to hear places that these drugs fail. We are going to get really political about cost at some point. Because I mean, if there's not another equity issue quite like this one in healthcare, this cancer treatment and this, and you know, it's like this is bananas. But there's so much more here and we could sit here for another hour with you. Jillian we are so happy to be in conversation. We loved your book the Hormone Loop. Vanessa and I are both doing in person events with you and we will of course share your website and book information and links to all those things in the show notes and we we are thrilled to have you be a two time guest on the podcast and we hope you will be a three time guest on the podcast.
- [64:40]
C
I would be delighted.
- [64:42]
B
Thank you so much for having me.
- [64:44]
C
Thank you so much for listening. You can email us with questions, feedback or Episode requests@podcast.com if you want to
- [64:55]
A
learn more about what we do to make this whole stage of life less awkward for everyone involved. Our parent membership, our school health ed curriculum, our keynote talks and more are
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C
all@lessawkward.com and if you want products that make puberty so much more comfortable, visit myumla.com.
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