Independent Insights, a Health Mart Podcast

New GLP Data for Sleep Apnea and Weight Loss

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GLP1 usage is on the rise. This week on GameChangers, we discuss the latest data on using GLP-1s for sleep apnea and weight loss.
 
The GameChanger
Several new studies suggest GLP-1 and GLP/GIP medications have positive clinical impact on sleep apnea and weight loss.

Host
Jen Moulton, BSPharm
President, CEimpact

Guests
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health

Jake Galdo, PharmD, MBA, BCPS, BCGP
CEO
Seguridad

Reference
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity
Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity

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CPE Information

Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Discuss the use of GLP-1 medications in the treatment of obstructive sleep apnea.
2. Discuss the relative weight loss in a recent study between a GLP-1 and GLP/GIP drugs.

0.05 CEU/0.5 Hr
UAN: 0107-0000-24-238-H01-P
Initial release date: 07/29/2024
Expiration date: 07/29/2025
Additional CPE details can be found here.

Speaker 1:

Hi, health Mart Pharmacists From your education partner, ce Impact. This is Game Changers. I'm your host, jen Moulton, and each week we have a conversation on a hot clinical topic that will keep you current in practice and position you as a resource for prescribers and patients. Thanks for listening in. Thanks for joining us today as I sit down with pharmacists Geoff Wall and Jake Galdo to dive into some new research on quite possibly the most talked about prescriptions available right now. You guessed it GLP-1s. Hello to both of you. Hello.

Speaker 2:

Hey Jen, hey Geoff.

Speaker 1:

Before we get into it this morning, I just wanted to set the stage a bit. First of all, let's clear the air about GLP-1s. I feel like there are two types of people in the world right now those who are on a GLP-1 and those who want to be on a GLP-1.

Speaker 3:

Yeah, I think that's pretty much about right.

Speaker 1:

It's crazy. It's just this crazy phenomenon and we're in the middle of it, so it's so fascinating to watch. We did a podcast a couple months ago on compounded GLP ones, um, and it was so good because I think there's still still a lot of misinformation and misunderstanding about what's legal, what isn't, you know, reputable compounding sources, all of that. So we did provide a link for that in the show notes, um. If you haven't listened to that one, I highly recommend it, um. But today we are actually talking about, um, a couple of areas of recent research, and that is comparing the effectiveness, specifically on weight loss, with semaglutide and terzepatide, and then also some new research on sleep apnea, which would be huge for indication, quality of life, possibly insurance coverage, all the things. So I am going to let both of you, as the experts, get into it today. Let's actually start with sleep apnea. Dr Wall, can you get us into that?

Speaker 3:

Yeah, absolutely. It is worth noting, as you were pointing out, that we have tons of people on them and tons of people want to be on them. I was reading a stat the other day that says one in nine Americans is on either semaglutide or terzapatide. So I mean, you're talking, 45 million Americans are now on these medications Consistent with people I know yeah.

Speaker 3:

Unbelievable. So anyway, yeah, so you know one of the things. I mean it's one of those. I think we're at the point now where we just have to do a GOP update every month or every two months, because there's a plethora of new studies showing, I think, in the end, how terrible obesity is and the impact that it has on a wide variety of disease states, and one of those big ones, of course, is obstructive sleep apnea, which is something that lots of patients deal with.

Speaker 3:

And you don't necessarily have to be obese to have obstructive sleep apnea. But I think it's a fair assessment that almost everybody who is morbidly obese has at least some apneic spells when they sleep. So you know you don't have to be, but it certainly increases the risk. It is exactly what it says it is. You have points during the night where you either completely stop breathing or you're breathing very shallowly and are not getting enough oxygen in, and this leads to chronic hypoxia, hypercapnia and recurrent arousals. You don't actually get any real deep sleep because you're constantly being kind of woken up because you stop breathing. The body realizes that and kind of kicks you awake. It's also associated with some pretty bad outcomes long term, most notably sudden cardiac death and in morbidly obese patients. This is one of the reasons why they're just found dead one day in the morning. It's just that they had multiple sleep apneic episodes and that triggered a respiratory arrest or a cardiac arrest. So there's definitely a mortality associated with obstructive sleep apnea, but even going beyond that, it's an increased risk for cardiovascular death and lung disease and all sorts of stuff. So you know it's a bad, bad disease and it flies under the radar, I think of pharmacists and most, even most physicians, because unless you're a pulmonologist you really don't deal with it all that much, even though 900 million Americans are affected worldwide and about half of those actually have moderate to severe disease.

Speaker 3:

And they measure depth or severity of disease by the apnea hypoxia index, which is simply just how many episodes of apnea or hypoxia do you have per hour while you're sleeping. So you have to do it during a sleep study and in fact most insurances won't even pay for things like pap therapy unless you demonstrate moderate to severe obstructive sleep apnea and moderate to severe episodes of that sort of thing. So now there are treatments and again, pap is by far the most common gigantic, tight-fitting mask that literally forms a seal around your nose and mouth and then uses positive pressure ventilation to keep the lungways open while you're asleep and dramatically decrease the number of apneic episodes. But if you have it's loud, a lot of people don't like a tight-fitting mask on their face. It makes it hard to sleep and if you have a claustrophobia in particular, it is very difficult because it literally feels like something is stuck to your face that you can't get off. So many, many patients are prescribed sleep apnea or a pap therapy for sleep apnea and they just don't use it because they can't, so it makes it very difficult to sleep.

Speaker 3:

There are a few surgical options, but they don't work all that well and many of these patients are high risk because they're obese. So a lot of times the ENT surgeons won't take a swing at them with surgical procedures just because they're not good, operable risks. So you know we have a few treatments. In the end, the treatment that works for everybody, of course, is a permanent tracheostomy, but, as you might imagine, not a lot of people want to walk around with a hole in their throat all day long. So in the end we have some options, but none of them are optimal and we certainly don't have any medication, so there are no currently FDA approved medications for obstructive strep apnea. There have been a couple of studies in the last 10 years that have looked at non-stimulant drugs for narcolepsy or for ADHD, and I've found a little benefit, but all those studies have been kind of small. Only a couple of them have been randomized and controlled, so that hasn't really taken off. So in the end we really don't have any good, solid data looking at medication benefit with obstructive sleep apnea, and so it seems to be how do we attack this?

Speaker 3:

Well, rather than trying to attack the apnea part, let's attack the big risk factor, which is obesity. It is the number one risk factor for obstructive sleep apnea, and as weight goes up, not only does the risk of obstructive sleep apnea go up, but so does the number of apneic episodes you have. So it stands to reason that weight reduction may play a benefit in, if not eliminating obstructive sleep apnea in patients, certainly reducing the number of apneic episodes they have at night, and that should have a whole wealth of benefits, right? So this it's actually two studies with the paper which we have on our show notes looked at terzepatide or Mongero, and we're going to talk a little bit later. How you know, we kind of lump all these drugs together. It's worth noting that Terzapatide is a GIP as well as a GOP1 drug and we'll be having a triple G drug here probably coming out late this year or early next year. That's a GOP1, a GIP and a glucagon receptor drug that will be coming out as well.

Speaker 3:

But the bottom line they wanted to ask in this question is you know, does weight loss improve or reverse obstructive sleep apnea? So they did this with two randomized placebo-controlled studies comparing and basically comparing placebo to terzapatide in patients with obstructive sleep apnea. Now the names of the studies were the Surmount OSA studies. I suspect nowadays there's an entire industry out there that tries to to pretzel a fancy sounding word into a trial and make it sound like it has something to do with the study. But that's what they did. Here is from out osa they.

Speaker 3:

This was two randomized studies. The first one was in patients who met the criteria for severe obstructive sleep apnea, were obese, so they'd have a bmi of over 30 and and had been prescribed PAP therapy but didn't tolerate or didn't want to use it. And then the second study in the Sturmaut-OSA series was patients who were tolerating PAP therapy for at least three months prior to being in the study. So they looked at both patients who do tolerate and don't tolerate that. Basically, inclusion criteria as I mentioned, they had to have moderate to severe obstructive sleep apnea. That is defined as an apnea hypoxia index greater than or equal to 15 events per hour. So that means 15 times in an hour these people stop breathing or they breathe so shallowly they become hypoxic. And again they had to be a MI of greater than 30.

Speaker 3:

A key exclusion criteria is they couldn't have type 1 or type 2 diabetes, which is kind of weird. I mean you would think the majority of these patients would probably have type 1 or type 2 diabetes. I understand the reason for doing that because again, you didn't want to look at some. You know we'd already know these drugs were approved for diabetes when this restarted. So I understand why they wanted to do that to make the trial more clean. But something tells me they probably had difficulty recruiting for this study because of that, because I suspect many of these patients have type 2 diabetes. They couldn't have already been on one of these medications or had lost more than five kilograms in the three months prior to screening. They couldn't have surgery for obesity. So no bariatric surgery or anything that would make it difficult for them to use pap therapy. So like facial trauma, something like that.

Speaker 3:

They did a four-week screening period and then after that in both studies they were randomly assigned to a one-to-one ratio to receive terceptide or placebo subcutaneously one week using the autoinjector, and of course they were given lifestyle modifications back off 500 kilocalories a day try to exercise, stuff like that. Then they measured the apnea hypoxia index by laboratory polysonography. So again they had sleep studies at screening at week 20 and week 52. And this was a year-long study which I completely agree was the right thing to do. The primary endpoint in the study was the change in the number of apnea hypoxia episodes from baseline. So in other words, if you had 20 at the start, at the end of a year, how many hypoxic episodes did you have per hour after the end of the study? They also looked at numerous, numerous other secondary outcomes and the number of patients who had at least a 50% reduction in their AHI. Patients who basically were cured of their OSA basically had fewer than five hypoxic episodes per hour. And then they looked at a number of quality of life measures. Probably the most important was the Epworth sleepiness scale. So this is a validated scale that looks at how much daytime sleepiness interferes with a quality of life in patients. There was a couple other quality of life surveys just looking at patients' perceptions of quality of sleep. So in addition to hard outcomes, they also took a look at outcomes that patients I think would think are pretty important as well.

Speaker 3:

Study went on from 2022 to March 29, 2024. They had a total of 469 patients who were randomly assigned to either receive terceptide or placebo in trial one or in trial two. So the study itself was relatively small. Again, they only had about 460 patients across two studies, so basically in four groups. You may wonder why that is, and I think they suspected that the benefit of the drug was going to be pretty big and so their power. They realized they didn't need a ton of patients to have power to show the difference between these and that's pretty much what they found. So the overall number of patients was relatively small at about 460.

Speaker 3:

As far as baseline characteristics, they are about the patients you would expect average age 50, about a third of them were female. Bmi was 40 or plus in almost all patients in the study and the number of they almost all had severe obstructive sleep apnea and in fact the average number of hypoxic episodes or apneic episodes per hour was 50, five to zero in these patients. So if all you need is 15 to be considered severe, these guys had really bad obstructive sleep apnea. That kind of sets the stage for what they found in the study and, as you might imagine, they found incredible benefit with the weight loss associated with tersepidite. So when they took a look at the average drop in the number of hypoxic and apneic episodes per hour, it decreased from 50 to 25. So it cut them in half in patients who are on the tersepidite group, whereas it only decreased five in the placebo group, and that was true across both studies. So again, it basically cut the number of apneic episodes in half pretty much across both studies, whether or not people were on PAP or not. 50% decrease in their AHI score, with 70% in the tricepitide group in the first study and 86% in the tricepitide group in the second study. So you know the vast, vast majority had a 50% decrease in number of apneic episodes they had. Now you could argue well, that still puts them at severe, and it does. But I mean you know, as you might imagine, the number of apneic episodes. The decreased number of those is going to improve outcomes, as you might imagine, and a small percentage of patients ended up with less than five apneic episodes at all at night and per hour per night, and so I mean I wouldn't. You know, cure might be a big word, but for all intents and purposes they did not clinically have obstructive sleep apnea anymore.

Speaker 3:

Body weight, as you might imagine, was what drove this. In both studies patients lost between 18 and 20 kilograms on average. So that's pretty impressive, whereas sleep arms only lost about two kilograms. So again, losing 40 pounds is definitely going to make a big difference here. As far as improvement in quality of life across the board, they found that quality of life improved, daytime sleepiness plummeted and overall quality of sleep really, really improved as well. So I mean pretty much across the board.

Speaker 3:

There were benefits from being on Terzapatide in the cohorts of patients. As far as safety is concerned, they had two adjudicated, confirmed cases of pancreatitis in the trial. They were both in the terzapatide group. It's a little concerning because, again, there wasn't a ton of patients in this study, so kind of keep that in mind. But again, remember that, as I understand it.

Speaker 3:

The current thought is that the pancreatitis caused by the GOP1 drugs is not because the drugs themselves are toxic to the pancreas, but because when you lose weight rapidly you get gallstones and gallstones are a cause of pancreatitis. So I think you know it's one of those things where where I think if you just keep an eye on that, you start developing right over quadrant pain as you're losing weight. You know you may be able to take care of that surgically long before you ever get in trouble with pancreatitis. Really no other serious adverse effects except for the typical nausea, diarrhea and constipation that was found, and even that, interestingly, wasn't all that much higher than in placebo. So I thought that was kind of interesting. So in reviewing the study, the authors, of course, are very pleased with the outcome, and I think they have a right to be. I mean, this was a well-done study. I didn't see any real problems with it or issues with it, other than the type 1, type 2 diabetes thing, and so this will almost certainly, and the makers of Migerol are looking for an FDA indication for this, and so, yes, this may well be the first study ever to be approved for obstructive sleep apnea.

Speaker 3:

Now the $64 question, of course, and Jake lives in this world, so I want to see what you have to think of and see what he thinks about this is. You know, of course we're always dealing with cost and availability with these medications. I guess my question is if you work for one of the third parties, do you say to yourself pap therapy ain't cheap CPAP most people don't buy their CPAP machines. They rent them and have to be clean and all that other stuff. They need equipment and supplies for it. I'm not sure it's the cost of what Mongero is a month, but I know that it ain't cheap either. So I mean, is it possible that this calculation may cause insurances to be a little more lean in covering terzapatide in obstructive sleep apnea patients?

Speaker 2:

So that's a lot to unpack. Geoff, you gave me a lot to think through. Thank, you and I'm not going to answer your first question initially, because I want to go back to a couple things that I heard that I wanted to call out. One is you called out 900 million people in the world with sleep apnea, which is a surreal number, and I never really gave it full appreciation. That's a lot.

Speaker 3:

That is a lot of people. I mean, if there's 7 billion people on Earth, that means essentially one in seven humans has obstructive sleep apnea.

Speaker 2:

Right, which is just so surreal. Yeah, it is, and so I think that in some ways, that's a diagnosed number, and so this emphasizes our ability to just under the fact that we underdiagnose things, we don't know what's going on. So this is a big problem that we're probably not talking about. The other kind of correlation that I want to call out is like in the study design, you talk about only people that were overweight with sleep apnea.

Speaker 2:

We ignored the diabetes, which is fair, because we wanted to focus in on the sleep apnea, which is a really important, crucial point, because, you've mentioned, there's no approved drug for it. So it's like they had to be as clean as possible if they're ever going to be the first approved drug. And then you start to think about it and it's like, well, if you look in the literature of like the disease that is sleep apnea, you know that it causes obesity because we're not sleeping. Because we're not sleeping, we're not getting healthier. So it is such a vicious cycle that it's nice that we have this thing that can disrupt it, which then gets us into this product itself One. I don't know if anybody else caught it, but you said the study ended in March of 24. That was a whopping like two to three months after. So if it ended in March of 24 of this year, that means like two or three months later they're publishing this article like they were prepped for this, because they knew this was significant.

Speaker 3:

And it really is. Yeah, and I suspect that the New England Journal editors you know not being idiots went oh my God, I mean this changes everything, or has the potential to change everything, you know. So I'll bet you this went right to the front of the queue.

Speaker 2:

Yep, and then it gets into the drug itself. So it's Terzepatide, right? You've mentioned that a couple of times which actually is known by a couple of names. It is known by Manjaro for diabetes, it's known by Zepbound for weight loss. So then I'm guessing it's going to be March bound breezy, something for for happy, right that's going to be exactly the same thing, and what's also interesting is that sleep well, it's the same dose.

Speaker 2:

I don't know if the study did too much about this, but, like when you look at the diabetes indication, this obesity indication, it's the same dosing, which is really kind of crucial, because that addresses supply access Right. Right, they're looking at efficiencies on how to get the drug out there, so I think sulfide will level out. Ultimately, though, it's the cost Right, and I think the hardest part about this is our healthcare system is bifurcated in looking at drug costs and healthcare costs, and we separate them when really they should be under the same umbrella, and sometimes we look at them under the same umbrella, but for the most part we don't. And so, if you ask, from a pharmacy perspective, am I going to be able to adjudicate the claim? No, because the PBM is going to say I don't want to pay for that, I got to drive down drug costs. But from the medical side, they should want to invest in the drug because it's going to save them.

Speaker 2:

On the other side of the equation, exactly, the challenge here is you know you can look at some of the ICER data with like quality, you know metrics, what's the cost effectiveness per one quality and all that jazz, but I think it really boils down to can we invest in our society, in our patients, in our neighbors, our loved ones, our husbands, our wives or whomever? And this isn't just about the person with sleep apnea, I almost argue it's the person sleeping next to the person with sleep apnea, because now you don't have to hear that CPAP machine.

Speaker 3:

Or you know a lot of people, of course, snore really bad when they have obstructive sleep apnea and this will help with some of that as well. So and and you know, it's important to note that you know again, almost everybody when we sleep we'll have occasional apneic episodes. I mean, that's just that's, that's just part of the normal sleep cycle. But you know, you know, and so last night, you know, both of us probably had a couple of times where you know we, they became hypoxic or we stopped sleeping or stop breathing, but it doesn't become.

Speaker 2:

I'm like a prince I don't snore, I don't make any noises.

Speaker 3:

I'm sure your wife is happy about that. Yeah, it's part of normal sleep patterns for humans. But again, this and a couple of other things people have abnormal or unusual anatomy of the neck and the throat and the nose and all that. But again, you know, sleep apnea or obesity, you know, makes all that worse by 100. So, no, you're absolutely right. But in any event, yeah, look, you know, even though PAP machines are part of the medical benefit, not the pharmacy benefit, you guys need to put your heads together because your plan is spending this much on PAP and you know, not only will you get the benefit of obstructive sleep apnea, but you're going to get the benefit of less insulin. You're going to get the benefit of, you know, these patients not going on to have a heart attack, not going on to have chronic kidney disease, et cetera, et cetera. You know it isn't just obstructive sleep apnea, they're going to benefit really across the board. So, yeah, it'll be interesting to see what happens, and apparently there is.

Speaker 3:

I was just reading day before yesterday that there's a I think Pfizer's coming out with an oral version of Terzepetide that is already in phase three. So we'll see. I think that might help some, I don't know or it may not help some. I mean the other part of the conspiracy theorist in me, which I'm not much of one is you keep coming up with new names and new indications and, of course, that's one of the patent lawyers. One of the big arrows in their quiver is that you might lose the patent on Zepbound, but you, one of the patent lawyers, you know one of the big arrows in their quiver is that you know you might lose the patent on ZepBound, but you're keeping the patent on all the other stuff. So it'll be interesting to see how that kind of goes. So that's this study, that's the study looking at these two drugs in this drug for sleep apnea.

Speaker 3:

The other study that has garnered a ton of media attention I've seen it on Newsweek Time, a lot of the online outlets, good Morning America Today all that stuff is a study that looked at terzapetide versus semaglutide for weight loss, so trying their best to compare the two drugs for weight loss, and this was just published, actually just last week, in JAMA Internal Medicine. Loss, and this was just published, actually just last week, in JAMA Internal Medicine. And you know, jake, as you pointed out, you know we tend to lump all these weight loss peptides into one big bucket. But yes, they are really different drugs. The GOP1 drugs are in one bucket, the GOP GIP drugs are kind of in a second bucket and, as I said, now we'll be having a third bucket with the triple G drug, glp, gip and glucagon drugs. That'll be coming out soon too. So you know we have, we have, you know, multiple targets here and, and I suspect over time and you know if I had to look in my crystal ball there may be a point where you know you need to lose a little bit of weight. You're on a GLP-1, kind of a lot of weight on terzepatide, a whole lot of weight on the 3G drugs and maybe even at some point you titrate down right, because if the triple G drugs are super expensive and eventually the GOP1 drugs will go generic, get to your target weight and then switch to one of the other ones to try and maintain weight loss. And of course there's a million studies to be done along those lines as time goes on. But in this study they basically aim to compare on treatment, weight loss between terzapotide and semiglutide in patients in a large clinical population. And again, the big thing they wanted to take a look at was the likelihood of achieving 5, 10, or 15% greater weight loss and then that overall change in total weight loss at 12 months.

Speaker 3:

This was not a randomized controlled trial, and certainly the makers of semaglutide have pointed that out in their rebuttals to this. They actually use the Truveta data set, which many of you records from a collective of US health care systems, and that they've agreed to submit their data to this, to this gigantic database, and it collects, you know, demographics, encounters with physicians and providers, diagnoses, vital signs, weight, medications, they're on laboratory tests, et cetera, et cetera, et cetera. So, considering that we are not a single-payer healthcare system, this is actually one of the better databases to do these kind of studies on. But that's what they did, is a retrospective database study using the Truveta data. They included patients who are new users of truzepatide or semiglutide who are either overweight or obese, regardless of having type 2 diabetes, in the study. It's worth noting that they use as their first time index for using trisepatide when it was released, a period in the market where it hadn't yet gotten its indication for weight loss, and so a lot of these patients did in fact have type 2 diabetes. That was considered the treatment initiation date and served the study index guide.

Speaker 3:

They did not include patients who had previously been on any medications in this class. Patients were adults, as you might imagine, and they had to have regular interactions with the healthcare system, where they had their weights checked every single time. They were a little bit cagey about what the exact definition of that was, but basically they wanted to make sure they had a number of data points in these patients. Not, they got one, a weight measurement at day one. They got another weight measurement at the end of the study. Right, there was no, there was no intervening things, basically. So so they looked between May 1st 2022, which was the month that True Zapotite was approved, to September 30th 2023.

Speaker 3:

As I said, they had to be overweight or obese, based on their BMI, and then they were classified as having type 2 diabetes if they had that ICD-10 code or they were on any medication that was only for diabetes. So that kind of makes sense. Their primary outcome was on-treatment weight loss and they looked at multiple time points during the kind of makes sense. The primary outcome was on treatment weight loss, and so, and they looked at multiple time points during the course of the study and then, like all sort of weight loss studies, when you're looking backwards, they had to control for a wide number of confounders. So these propensity score matching to balance things like gender and age and baseline weight and race and disease states that might affect weight and etc. Etc. You know it's worth noting that that the more weight you have to begin with, the more weight you're probably going to lose when you're, when you're put on these medications. Right, they also once they compounded or made their propensity match model.

Speaker 3:

They also did several sensitivity analysis analysis. So they ran the data over and over again, trying to look at different you know if there's things were different in the propensity score matching to see if there was any differences there. Basically and one of the big ones there was a stratified patients with and without type two diabetes to see again if there was a difference in weight loss. The safety outcomes they looked at moderate to severe adverse effects, which included not just diarrhea and dyspepsia and GERD and stuff like that nausea. They'll also look at things like bowel obstruction, gallstones, pancreatitis, gastroparesis as well, and they pulled all that again from the EHR data. Mild adverse effects such as nausea and vomiting were not included because of course it's hard to measure, that it may not get written down in a note and patients won't usually get an ICD-10 score for that, so that's kind of worth noting.

Speaker 3:

In the end they had 41,222 patients who met their criteria. The vast majority are on semaglutide because, again, when they started out it turns out that that hadn't even been approved for type 2 diabetes. It had actually just been approved, so there were going to be fewer patients on it. After they were done with the propensity score matching, they noticed that the population on the whole was white, female, had college educations, which means they could afford or had good insurance to afford it. The people initiated terzapotide actually had a lower prevalence of type 2 diabetes, interestingly. But other than that it was fairly similar between the two. Mean weight was similar between the two at 110 kilograms, so about 220 pounds.

Speaker 3:

So when it was all said and done, what did they find at the end of the study? At the end of the study they found that 62% of patients on terzapatide, versus 37% of patients on semaglutide, lost at least 10% of their body weight. 42% of patients on terzapatide, versus 18% of patients on semaglutide, lost 15% of their body weight and 15% of terzapatide groups, compared to 8% of the semaglutide groups lost 20% or more of their body weight at 12 months. So across the board, a TERS epitope was more effective at overall weight loss, whether it be 10, 15, or 20%. As you might imagine, the numbers go down as the number of weight increases.

Speaker 3:

When they did the sensitivity analysis and they kept running the data, they really didn't find any big differences. So across the board, whether you had type 2 diabetes or not, what your baseline weight was, what your gender was, it didn't make any difference. Across the board, you were more likely to get significant weight loss with terzapotide versus semiglutide. Now of course, they also looked at the side effects and I think one of the big things that surprised the authors was that there was no significant difference in adverse effects, and that can include, again, all these major adverse effects that they caused. Now that may be just because the overall incidence of these drugs is very low, or it may kind of dispel the myth that terzapatide, because it causes more weight loss, may have more adverse effects associated with it. So they basically found that.

Speaker 3:

Now you know, they note, and again the company that makes Tersabatide has said you know, this is not a randomized control trial, so it's not hypothesis proving, it's hypothesis generating. And they're right. And you know, large media organizations have ran with this and said you know, tersabatide is better, this is what we should be using, et cetera, et cetera, and you cetera, et cetera. And to their point, there's always going to be residual confounding You're not going to be able to get rid of in a retrospective study. You can do propensity score matching or logistic regression, but in the end there's always going to be some confounders that you're not going to take care of. So that's kind of why. But in the end the findings are what the findings are.

Speaker 3:

And it is worth noting that, even though there are no head-to-head studies of these drugs and probably never will be, if you just take a look at overall weight loss in the phase three studies that both drugs had, on the whole, trisepatide seemed to cause more weight loss in their studies than semiglutide did in theirs. So they basically said in know, in this large database study, terzapatide does seem to be associated with more weight loss, especially at the 10 and 15% weight loss levels, and that you know. You know, maybe we should target terzapatide for the more obese patients. Like I said, are we going to reach a point where we're stratifying patients by their baseline weight. We want to get the most weight loss, so we pick the more powerful drug to do that. So, jake, your thoughts on all that.

Speaker 2:

Well, I think the biggest takeaway is what you've been kind of highlighting throughout the episode, is that there's a difference between the two products. One is solely a GLP, the other is a GLP-GIP, and I think that that goes to show in some of the outcomes that we have here and it also helps raise the awareness that they're not the same, even though we in the media we kind of treat them the same. You know, I've had multiple colleagues and friends reach out and say hey, I've got this patient on one drug and I need to do a dose conversion to this other. What do I do? And if you take any of the traditional GLPs semaglutide, loraglutide, exenatide, delaglutide, any of them and you say I need to switch over to terazepatide, it is not any type of one-to-one conversion, it is just start over. And it makes me think about all of our stents. If we switch somebody from Pravastan to Rosubastan, you might say well, pravastan 80 has LDL lowering of 15%, which is equivalent to Rosubastan 5. So the conversion is Pravastan 80 to Rosubastan 5. And that doesn't exist in this world.

Speaker 2:

Here again, because trisepatite is a GLP-GIP and I think that that's like the crux of this is that in some ways we're actually not comparing apples to apples. It's almost like an apple to an orange a little bit. But we have just created this media craze, as Jen said at the very beginning. We have people that are on GLPs or people that want to be on GLPs, but it's really people that are on GLPs, people that are on GLP, gips and those that might want something of the above, and I think it's that that understanding that these are different helps us raise this, this awareness that you know it's not parody. Yeah, maybe someone just wants a little bit of weight loss and says semaglutide might work. Maybe somebody wants some really efficacious weight loss, so I need trisepatide. Maybe someone hates nausea and vomiting so they want to go with the lower efficacious drug in some regards because there might be less severity of some of the side effects.

Speaker 3:

And again in my mind's eye, I see where, unless again, some catastrophic side effect gets discovered with, with, with these medications and frankly, even if, even if it is at this point, so many people are on them, I think a lot of people would just take the chance, take their chances. I do see where, like you said, I mean you know frankly, you know in 10 years the vast majority of Americans are going to be on these drugs, right, and I think you know you're going to have a titrated system, right? You know people who are. You know their BMI is 28, 29, and we really want to get you and you've tried exercise and weight loss and or exercise reading, right, you just can't drop that last 20 pounds to get you into a normal BMI. You know they're on, maybe even you know these. You know kind of weaker GOP1 drugs that you mentioned. And then, yeah, okay, I need to lose 5% to 10% of my body weight, keep it off. And maybe semi-glutide, I need to lose 10% to 20% of my body weight. Then trisepatide I need to lose more than 20% of my body weight, perhaps, and certainly the early studies suggest the triple G drugs.

Speaker 3:

And again in my mind's eye, I see where you know most Americans are going to be on this and you know. Again, you could argue you know, there's, there's, there's definitely some sociological impact there. I mean, you know we're, we're the first, you know, we're the first civilization in history that has such plentiful access to so much food that we need to be on medications to keep us from eating it. It's just, yeah, it's pretty interesting. So I think that's what we got, jen. What do you think?

Speaker 1:

Yeah, so interesting, and I know you touched a little bit on it, jack. But what do you anticipate and I think it's in the fall right the triple G? What do you think that's going to do to this marketplace?

Speaker 3:

It's a good question and, jake, I'm sure you have some thoughts too. Again, the early data and again, you never know between phase twos and phase threes. Or you know if I had a nickel for every oh my God, this looks great. Phase two stud drug made it phase twos that gets killed in phase threes. I have a lot of money actually If the phase three studies bore out what the phase two studies have shown.

Speaker 3:

These drugs are getting weight loss comparable or above to bariatric surgery. I mean, people are losing 20, 25, 30% of their body weight, just unbelievable amounts of body weight, and I would say that that's going. Again, it's to see what assurances do, what weight loss experts recommend. It's interesting to know that, to my knowledge, there are no guidelines on weight loss medications by an official body, by the American Obesity Association or, you know, american Academy of Clinical Inheritance or anything like that, and we need some. I think, and especially when the GGG drug comes out, they're really going to need it and I think that's what's going to happen.

Speaker 3:

Is you're going to see? You know, as I think is going to happen, is you're basically going to see drugs stratified by the amount of weight you need to lose. Now, of course, you know, you're going to have people who think they need to lose more weight than they do, and even now there are some reports of people with muscle loss, you know, because they're losing so much weight so fast that they're starting to lose muscle mass. So there's there's there's a lot of things we got to answer with that, but I think that's what that's, what I envision is going to happen is that you're going to kind of take the patients who really need to lose the absolute most amount of weight and that's who's going to preferentially get targeted with the triple G drugs.

Speaker 1:

Yeah, jake, any last parting, thoughts.

Speaker 2:

I think the only last thing that I would end us with is that obesity is a chronic medical condition. Yes, and it is amazing that we have therapies to treat it now, just like we're now looking at therapies to treat sleep apnea. You know, if we don't treat obesity like the chronic disease that it is, an untold number of Americans will be obese in the next decade when you look at the 2030, 2040 guidelines and goals and the trends, and it is just scary. So it's wonderful that we have these opportunities, and I think insurers need to better assess the pros and the cons to make sure that we can improve access to this, these therapies.

Speaker 3:

You know, I'll, I'll, I'll echo that too. I mean, you've got a lot of influencers and a lot of the the you know people on social media, you know the life coaches and stuff. You know you don't want to cheat and get put on these medications and that, I'll be frank, irritates the living hell out of me, because it's like you know. You know, when someone has hyperlipidemia, we don't say, well, you know, you know, you don't want to cheat and be on a statin right. When somebody has hypertension, we don't want to say, oh, you don't want to cheat and be on you know Losartan for your high blood pressure? It's the same thing. You know, it's a chronic disease. We need to treat the chronic disease.

Speaker 1:

Yeah, and so many implications. I mean, you know we're talking about it today with sleep, it's just all. It's such a cycle. So this is great, and I think you're right, Geoff. I think we probably need to do an update on some GLB ones because, like you said, there are no guidelines yet. They're you know, they're just it's such a new area, that thing. You know, new research is coming out all the time and I think we're just going to continue to learn more and more, so we will keep you updated through Game Changers. So that's it for this week and this topic. If you liked this episode, please be sure to share it with a friend or colleague. And that's it for this week. Be sure to log in to Health Mart University to claim your CE credit for this episode. As always, have a great week and keep learning. We'll talk to you next week.