Episode 377: GLP-1 Anti-Obesity Medications Update-Efficacy, Muscle Risk, and Future

25:29And so that's what we're seeing with the newer agents, like the one you just mentioned, what's being termed a quote-unquote triple agonist because it hits multiple different receptors. And again, setting the details of that basic science aside, hitting multiple receptors lets us target multiple different pathways to achieve the effects we want and add on additional beneficial things. We've talked about this before, for example, when we recently did like our blood pressure update. And I talked about how a lot of the time when I have a patient who's willing to do it, I tend to use multiple lower dose medicines to get the bang for my buck from multiple meds with less side effect risk.

26:03Same thing with lipid or cholesterol lowering therapies, using different medicines at lower doses that work in different ways, because we know that hitting different pathways that all kind of converge on a similar outcome, we can get a lot of effectiveness. And by keeping the doses on the lower side, if that's feasible for a given patient, then we can mitigate and avoid most of the tolerability type of issues. And so what we're seeing with these triple agonists and the data coming from ritatritride is that it is more potent, achieving now into the mid-20s on average, like 24%, 25%, say, weight loss, starting to compete with metabolic bariatric surgery efficacy.

26:41And then also having some seemingly unique aspects to it. the glucagon receptor that it targets. I've seen some discussion that it maybe like increases energy expenditure, maybe helps to accelerate, you know, the resolution of fatty liver disease as a result of that, maybe a little bit more lean mass sparing, which would be awesome as well. And so, again, I think the level of expertise and incentives at getting this right are leading to just phenomenal development of these things to get all the things we want with less and less of the things we don't want coming out. Yeah. Yeah. I found this, the development pathway, super interesting, mainly because, as you said, the incentives, it's like, oh, look, if we can make this work better with less side effects, yeah, we're going to do it.

27:21And it's like, wait, if big pharma was super evil, like that doesn't necessarily seem like the move there. But yeah, it would be interesting to see if RETA gets, you know, once it gets past all the phase three clinical trials and there's some better dosing and monitoring sort of profiles available for that. But yeah, it's out in the wild. People are obviously like using these research chemicals, which we're going to talk about shortly. Not my favorite thing, but we'll talk about that. Before we get there, though, Dr. Nadolsky, because of this pipeline is being just kind of pushed to the nth degree, there are some oral options coming down the pipeline.

27:58And I suspect, as I talked about earlier, that people are going to prefer an oral option compared to self-ejecting or whatever. What are you expecting from some of these oral options coming out? Yeah, there are two of them that are going to come out 6 to 12 months from now. They just actually just put on a fast track for Orforglypron. I used to say Orforglypron, but it's apparently Orforglypron. Whatever. It's a small molecule. Suppose a big, huge peptide that you have to inject or with the semaglutide oral, you have to put it in a special packaging that changes the pH of your stomach to be able to actually not break it down and absorb it, which I'll talk about in a second more.

28:42Orforglipron is a small molecule, so you can actually take it orally with food. You don't have to worry about drinking tons of water or anything, other medicines interfering that I know of. And it has around like 10%, 11 % total body weight loss. We don't have all those cardiovascular trial data like we do with the oral semaglutide, which I'll talk about in a second. But somewhere around like a 10%, 11 % total body weight loss, it's supposed to be cheaper because it's easier to make because it's just a regular molecule instead of a peptide that needs all this special transporting and things like that.

29:22So I'm kind of excited to see that because if it's cheaper, and we'll talk about the prices and stuff about people trying to maintain their weight loss and having to come off the medicine because of price, this might be something that would be of use there. and hopefully they do cardiovascular. I think they're going to do some cardiovascular trials to make sure, as we've seen before, other drugs where we thought were going to be really good. In the end, there might have been some bad things happening that we just didn't know about. And some of the oral drugs, oral small molecule GLP-1 drugs that didn't come to the market, they found some of these through the phase 1, phase 2 trials, which is a testament to why we do all these phase 3 trials and even further post-market surveillance.

30:07So that's Orforglipron, small molecule, not a large peptide. They can make it easier to make, cheaper to do. They have a ton of it stockpiled that they're ready to launch here. Again, I'm not getting paid by Lily, but it's excited. That's a Lily drug. The other one is high-dose oral semaglutide. So we already have this available in the form of a type 2 diabetes-branded drug, which is ribelsis, if anybody's heard of that. But that's been out for quite a number of years now. Not super popular, though. It goes up to 14 milligrams. This new higher-dose version, they're going to allegedly call it oral-wegovia.

30:45That's what I've heard through the pipeline, which I don't know. Whatever. Oral-wegovia is what they're going to call it. So it's high-dose. They actually studied it first at 50 milligrams. That's 5-0, 50 milligrams. So it's about a tenfold difference in absorption. I talked to a PharmD on my podcast all about it. So they put in 50, but then they found that the 25 worked pretty well. And it's around, you know, somewhere around 14%, 15 % total body weight loss. It's not bad, not a bad option. And they have that cardiovascular disease data that we can discuss here. But not a bad option, but it is.

31:26It has to be packaged in the snack package that allows your stomach to absorb it. Because otherwise, if you take an oral peptide, it gets degraded by your own stomach acids and won't be absorbed. It'll be broken up and everything. So they have to put it in this special thing. You have to take it with a tiny little bit of water in the morning, no food for a while. Now, the question of whether people would prefer it. So what's interesting is my patients almost love the weekly injection. It's because I thought the same thing. Maybe people would love taking just a pill. They love just because the needles are so small.

32:04They're teeny tiny. And some people are afraid of needles. I'm like, just do it. And let's see what happens. And they're like, I didn't even feel anything. So a lot of patients actually love the weekly injection. But I don't know. We'll see. I think really what it comes down to is price. If you can make these things cheaper, that's going to take the cake. Whatever is the most powerful, but then the expense really takes the next. Yeah, not that anybody's asking me to name drugs, but oral Zempic seems like a way better thing than oral Wegovi. Yeah, I know. Yeah, look, I'm available. If you guys need me to consult on drug naming, I'm here.

32:42All right, well, look, we've talked about some of the efficacy, very, very effective. but there are some cool other benefits to these medications that have been coming out. And I think there is some interesting stuff here, not only with like weight loss associated benefits and things like, you know, heart disease, a certain type of cancer and so on and so forth, but also weight independent effects. So like maybe these medications do something on their own to reduce the risk of either disease development or disease progression that's independent of weight loss. So Dr. Nadolsky, what have trials shown so far in terms of like the impact on heart health or cardiovascular health from these drugs?

33:23Yeah, so the semaglutide is the big one that we saw a couple of years ago. Actually, it's pretty much two years ago, the SELECT trial, at least the top line results came out. I believe the full study came out. But SELECT trial was Wegovi and those with a history of obesity and cardiovascular disease and not type 2 diabetes. So we've seen benefit in the past. My brother always talks about the LIDER trial with liraglutide. Now that was like whatever it was 10 years ago. So that was the first drug to show cardiovascular benefit in those with type 2 diabetes at high risk, cardiovascular disease. This was the first one that I know of that people did not have type 2 diabetes, but had a history baseline cardiovascular disease.

34:06And what they showed is a reduction in major adverse cardiovascular events. And they've done further analyses that show like it doesn't look like it's, it looks like it's mostly maybe at least two-thirds of it's unrelated or independent of the weight loss. And when you look back at studies, we thought that like around a 10 % total body weight loss, whether it was from lifestyle bariatric surgery, would lead to reductions in cardiovascular events. So that's kind of what they were thinking. But now with some of these other drugs, like they've had older GLP-1 receptor agonists. Albiglutide was one of them.

34:48That was for type 2 diabetes. But people didn't lose any weight, but they still improved their cardiovascular event reduction. like there's improvement there. So there are receptors all over the myocardium. There's receptors in our endothelial tissue. There's receptors, changes in our immune system. Something's going on with this GLP-1 receptor agonism that goes beyond just the weight loss. Of course, we're going to see blood pressure improvements. We're going to see lipid improvements and just overall mass in general, which may be a less strain on the heart. But like there's something else going on just from taking a GLP-1 receptor agonist.

35:29So for the heart, I think that's what's really exciting. We're waiting on terzepatide data. There's a terzepatide study similar, but they're actually doing it in primary prevention as well. I don't know. I'm sure you've all talked about differences between primary and secondary prevention. So primary would be preventing that first heart attack. from secondary is somebody's had a heart attack or heart event and you're preventing another one. So the terzepatide, the surmount MMO, they're looking at like, it's going to be really interesting. I think it's going to be positive though and good. Yeah.

36:05No, this is just a brief aside. You're hearing Dr. Baraki, Dr. Nadolsky, and sometimes myself talk about all these various studies that are very specific to a particular intervention in this case of medication in a particular population to come up with a particular outcome to see if that changes. Contrast this to mechanistic data in exercise science, where it's like, look, if you, you know, fast, then your growth hormone level goes up some percentage. And people are like, yeah, that'll probably lead to more muscle mass. And it's like, do you know how many steps you've skipped in the middle to get to that point?

36:41And in medical research, particularly in agents that have a lot of evidence and data behind them, you can feel quite confident in saying, look, if you are in this population, you have a high probability of seeing some level of this effect. And it's relatively well characterized, which I find very reassuring just to like, you know, if you're advising somebody on taking these medications or to not take these medications or other medications, it can all be useful there compared to it's mostly vibes. Like we have like a mechanistic like plausibility, but we don't have like good outcome data or the outcome data we do have is not good.

37:15In that case, you're like, I don't even know why we're talking about this, but just a brief aside. Anyway, I see this on, on threads. There was just, they're talking about this very quick tangent. People do this with drugs and doctors. I think it's because they don't understand study design and how to design trials to look at outcomes. So menopausal hormonal therapy, they're saying reduces cardiovascular events. It's like, it's a whole thing. We could do a whole podcast on that. And so Austin and I were going on threads. I saw, I noticed he jumped in and it's just, but it's not just exercise science.

37:48It's unfortunately a lot of other places too. Austin and I have, I think turned into Clippy from Microsoft Word, the little guy. So we're like, hi there. What do you think the best direct human evidence is to show that this actually, you know, I enjoy it. They show up in my feed and I always like it because it's always so funny. I'm always like, oh my gosh. Yeah, you and your brother, we like seeing your likes because it makes us feel good about what we're doing. It's so funny. So to Austin, what about other major organ diseases like that of the kidney and that of the liver? I know there's evidence coming out here.

38:21So what do we know on that front with respect to these anti-obesity medications? Yeah, several years back, there were just a broad policy about medicines that were being looked at for use in diabetes, that they were essentially all being required to look at cardiovascular outcomes, these things like heart attacks and strokes and things like that. But interestingly, we're also accumulating evidence in other very, very common organ system diseases. Obviously, as I mentioned, I'm sitting here speaking to you from the hospital where I have a ward full of patients with all of these things, be it cardiovascular issues, heart attack and heart failure, which have been looked at with these medicines, as well as various levels, degrees of chronic kidney disease, all the way up to dialysis patients.

39:01And then my least favorite and the most horrific is advanced liver disease, which is something that we see more and more of these days. So when I went through training, I saw boatloads of, for example, hepatitis C-related cirrhosis. Now that we can cure that condition, seeing less and less of that, but much more fatty liver disease that has progressed to steatohepatitis and then cirrhosis as a result, and then the complications of that. And so when this has been examined so far, for example, in the FLOW trial, looked at GLP-1 agonists and what they called kind of this kidney events, to borrow a term from the cardiovascular literature, things like progression of chronic kidney disease or death related to kidney related causes, these medicines are showing benefit in that realm.

39:46And then similarly, when we look at, for example, the rates of fatty liver disease or resolution or improvement in fatty liver disease, improvement in inflammatory markers around fatty liver disease, which would all, you know, lead to a reduction in the risk of progression to cirrhosis and all of those really horrific, you know, complications that I have the pleasure of dealing with in the hospital, the more potent these medicines get, the more benefit we're seeing on fatty liver disease. And that's what I mentioned earlier, the interesting kind of maybe unique aspect of RETA that you mentioned as one that can maybe increase some energy expenditure, maybe has some unique benefits on the liver, whether or not that ends up panning out and being fully accurate just the sheer amount of weight loss that these things can induce you know once you get well beyond seven and a half to ten percent of weight loss we can see essentially curing of fatty liver disease which is uh which would be great uh to to reduce the burden of chronic liver disease worldwide so not only heart but also kidney and liver like three of the major chronic organ system uh type of conditions that are often also comorbid they have led to this development of a new term that they're calling CKM syndrome or cardiovascular kidney metabolic syndrome that kind of encompasses all of these things, people having heart disease and liver disease from fatty liver and kidney disease as very frequently overlapping in patients.

41:04And we have increasingly potent and increasingly well tolerated agents in these medication classes that can somehow simultaneously benefit all of them, not only because they have a shared mechanism, but also because of some of these weight-independent effects that Spencer alluded to earlier. Yeah, maybe we can rebrand CKM as type 3 diabetes so people don't inadvertently refer to that as like dementia, which is definitively not the case. That's another like quack watch, red flag. If somebody calls dementia of any kind type 3 diabetes, you should just block and move on. Totally make these texts.

41:38Yeah, that's right. Before moving on to some of the side effects we're going to talk about, There is other areas of emerging evidence coming out for everything from like sleep apnea to addiction, some forms of cancer, so on and so forth. So I'll have both of you weigh in on this. I'll start with you, Spencer. What are some of these areas, these other areas where these medications could be effective based on emerging evidence? Yeah, so obstructive sleep apnea is pretty well established. There's a surmount OSA trial. That's why they've actually made it FDA approved for those with obesity and obstructive sleep apnea.

42:11Medicare even allows for it. We see sometimes a resolution in obstructive sleep apnea. People stop needing their CPAPs. It's not all the time. Weight loss doesn't always improve obstructive sleep apnea or resolve it as there can be some anatomical differences. But when you start getting that 10, 15 % total body weight loss, we start seeing reductions in the apneic events from obstructive sleep apnea. So pretty good data there. There's another drug called Q-Semia that actually, it's not FDA approved for it, but it's a fentramine-topiramate combo. So we do know that a lot of weight loss can result in improvements in obstructive sleep apnea.

42:53I do believe most of that is weight dependent. However, some argue there may be some other weight independent effects. It would be hard to tease that out exactly, but kind of interesting there. from addiction. So there is a there's a new another lily. I swear I'm not getting paid by lily, but they this podcast is brought to you by Biggs at Barbell Medicine. We spend a lot of time talking about what it takes to build a body that can handle high level performance. But the recovery and health side is just as critical. Over the last six years, an incredible team of health care professionals did something that most people thought was impossible.

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44:32And I had a, so funny, so stupid, but I had a viral TikTok a few years ago when I started using a lot of Manjaro. It was the type 2 diabetes version of terzepatide. When that first came out, I was using a lot of it off-label. And people right away were like, wow, this is so weird. I don't really want to drink alcohol. And I was like, really? So I actually published some retrospective data of all of the changes in alcohol intake from our patient population of like tens of thousands of patients. Kind of cool to see that. So I believe that we're going to see other addictive-like behaviors. People are not biting their nails anymore, maybe even some gambling, sex addiction type of stuff, opioid addiction type of things.

45:14The drugs have a strong response in the reward center of our brains. And it really sucks. So I think we're going to see addictive-like behavior improvements there. Other things, so anti-inflammatory things, so psoriatic arthritis, rheumatoid arthritis. Some of my patients notice, wow, I was on my biologic and it kind of helped me with my psoriatic arthritis, but it wasn't until I started trisepatide. Again, this is anecdotal. But when you go to Eli Lilly's research page of what they're looking at, the trials are doing, they are looking into this. So Big Pharma is not stupid. They're not going to pay gajillions amount of dollars to look into some silly anecdote.

45:52They're clearly seeing the signal too. So I think we're going to see a lot of really just interesting stuff there. I see gynecological improvements. People start having normalized menstrual cycles. There's GLP-1 receptors on the uterus, ovaries, and in the hypothalamic pituitary region. I don't know. There's some interesting stuff. Yep. Some of the most interesting stuff I've seen come out has to do with cancer risk reduction. And it almost seems like, not to get too technical or jargony, pleiotropic effects of these medications, They're just affecting multiple different areas. Look, if there's a receptor there or like something that these things can bind to, it seems to have a decent effect.

46:34Dr. Baraki, what's your take on this like cancer risk reduction? What's up with that? Yeah, I think that it's really difficult to study in the way it has been studied so far. You know, cancer is a very heterogeneous disease. There's so many different types of cancers they develop by way of so many different types of exposures and things like that. So like looking at acute leukemia, for example, and comparing that to, you know, estrogen sensitive breast cancer, they're like completely different pathologies. And so lumping these things into big buckets and looking at it in an observational way, which also lumps in a whole lot of other, you know, variables that are not being equally distributed in a randomized trial, makes it kind of tricky.

47:13I find it plausible that there could be some impact on cancer incidents, particularly among the adiposity associated cancers and things like that. But that's something that I would want, I think, higher quality data to try to tease apart. To what Spencer mentioned earlier, we already have, for example, some of that in sleep apnea. We already have that in osteoarthritis. We're looking or expecting that, hopefully coming soon in some of the addiction space. And, you know, I have some concerns around, you know, the judicious use of those medicines in the addiction space, knowing that, hey, well, a lot of the patients that I see, because I see tons of alcohol-related issues in the hospital setting, and I have a few, as we speak, who are not very well nourished, for example.

47:52And so then what's going to be the impact? They're not very well muscled. They're not very well nourished. They don't have high quality diets. They're not exercising. If I induce 20 % weight loss in this person whose diet is comprised mostly of alcohol, what's the impact going to be? So there's some thoughts and concerns, which is the lesser harm there, right? And in general, I'm trying to get people to drink less. And I will tend to accept a fair amount of risk in other ways because alcohol is like the most harmful thing that they might be doing. So there are going to be a lot of considerations around all of these areas.

48:18I share some of his observations around PCOS. There's also conversations around like maybe neuroprotection, dementia risk, things like that, that will also be super interesting because, you know, we've seen cardiovascular disease remains the number one killer, but on a per capita basis, rates of death from cardiovascular disease have been declining for decades now. We're making a lot of progress there with all the tools that we have at our disposal. Now we seem to have one that's going to be helpful for obesity and the obesity-associated comorbidities. the longer we live without dying of things like cardiovascular disease or kidney disease or liver disease the longer our lifespans extend it's going to be more and more cancer and more and more neurodegenerative disease and so if these have a favorable impact on those things that would be a win on those fronts as well so super interested to see how it plays out yeah what i'm hearing you say is that if we just take terzepatide or semaglutide you stack it with creatine effectively you're going to live forever.

49:1110 grams still. 30 grams. More grams. All the grams. Yeah, so many grams. All right. Well, let's transition to some of the side effects because with any effective medication, there are no biological free lunches here. There are risks and side effects. So let's discuss some of the common side effects and some of the rare but serious ones. So Spencer, what are the most frequent side effects that people should be prepared for? And how do you go about dealing with them in your practice? Yeah, by far, number one is nausea. Very common. We saw this very early on with exenatide or bieta and all the GLP-1 receptor agonists.

49:49In fact, many of the haters would say, look, people just lose weight because they're nauseous all the time and thrown up, which is plausible, I suppose, if people get sick from a GI bug and you don't want to eat, you lose some weight. And if you feel like that all the time, that can make sense. But But when you look at the data, it's pretty clear that the nausea is the highest in the beginning and then the longer you've on the medicine, it tends to go away for pretty much everybody. For most people, it's mild to moderate at first. Very once in a while, it's more moderate to severe where you have to intervene with an anti-nausea medicine.

50:25We try to minimize it with our diet. I have dieticians and we try to promote kind of a lower fat diet. Now, there's reasons why this may be higher fatty. So like chips, fries, pizza, burgers, wings, that type of thing may be increasing that nausea in the beginning. It could be because the gastric emptying is slowing. So you put more fat in the gut and then it's more having an increase in other things like CCK and other hormones that from the fat intake that can also increase nausea. So potentially, I don't know what, but lower fat diets tend to help minimize this. and maybe smaller, maybe more frequent meals, not to boost your metabolism or anything like that, but to help with the nausea.

51:09And you don't have to do that long-term. This is, again, the nausea is high in the beginning. When you look at the trial data, it doesn't matter what trial it is, some maglutide, trisepatide, they show the trial data. It's all peaked up in the beginning. And then as the trial goes on, the nausea goes down. Sometimes we have to do Zofran or Undansetron to help with the nausea. In general, though, most people don't have to do that. So So that's number one. I do see a lot of constipation. Unlike nausea, it's constant, so you have to get in front of it early. Lots of fiber, lots of fluid, physical activity, the very standard things we do for constipation.

51:46Sometimes we add a laxative or add some fiber supplements and things like that. But constipation is pretty common. Try to get in front of it to minimize that. But reflux, if you're slowing down the gastric emptying in your stomach, there's more of a chance for food and stuff to come back up to your esophagus, cause reflux. So we do see that. So people with a history of reflux, we're like, all right, we got to be careful here. You might get some worsening. Don't stop your omeprazole or whatever right now. Sometimes they need to add it back in for a little bit. Hopefully over time that improves.

52:22And generally we see that improve because that gastric emptying is higher in the beginning and then wanes or even goes down a lot at the end of, or while you're on the drug longer. We do see diarrhea, usually self-limited. Generally, we try to help people bulk up their stools if happy, but it's usually self-limited. Sometimes I do Pepto, sometimes I do Imodium. Generally, something that goes away over time. We see fatigue. A lot of people thought, oh yeah, you're not eating, you're going to be tired. There's something about the drug, and this likely has to do with the brain effects of the drug, the receptor agonism in the drug.

53:00We're talking about the dopamine where people feel like not as addictive, but sometimes it's got a pretty strong effect up there. Almost they feel like an anhedonia, like just kind of like they feel unmotivated and tired. That happens. Sometimes we've got to adjust the dose. Sometimes it's just at the beginning. The fatigue generally goes away by itself, though. And, you know, a lot of people argue over the cause of it, but it's likely in the brain. Some of it may be because you're not eating as much, but you'll feel it like a couple days after your shot and then it goes away after a few more days.

53:34Kind of interesting. Worst side effect, gallstones probably. We see that because of weight loss likely. There may be an effect of GLP-1 on the actual gallbladder and changes of how it's moving. We can see gallstones precipitate. But we see that with any type of weight loss, bariatric surgery. And from that, we can see, you know, the cholecystitis or gallbladder attacks, rarely pancreatitis. When you look at the, when you compare placebo to the active drug in these big, huge trials, they put them together in a meta-analysis. There doesn't seem to be a statistical difference between the drug and a placebo.

54:11But patients are like, yeah, it causes pancreatitis. So it's not different from placebo. So those are the common thing. I don't know if you want to, Austin wants to talk about the black box warning of thyroid cancer and all the scary things people talk about, but those are kind of the common things. Yeah, I was going to echo much of what you said. And the pancreatitis one is interesting for several reasons because pancreatitis is a relatively common condition. Like it's something that also just happens to people sometimes in general. It happens relating to alcohol use pretty often. It can happen relating to gallstone-related causes very often as well, and I see it very regularly in the hospital setting.

54:56And so given that there's a relatively high, what we'll call like base rate of people experiencing pancreatitis, that also increases the risk of like, well, also there's a high base rate of people getting put on these medicines. And so there's going to be a scenario where somebody gets put on one of these medicines and because they were just existing, they were going to get pancreatitis anyway. And humans, what we do in our brains is we tend to observe patterns and assume causation between them. Well, I started this medicine, and afterwards I got pancreatitis, so it must be that one caused the other.

55:27And that is a reasonable hypothesis to have, but that's also why we benefit from having controlled trials. And that's where this interesting observation comes from in the controlled trials, that when we compare people on drug versus on placebo, we don't actually see a significant difference in that pancreatitis risk, even though there is a higher risk of developing gallstones relating to the rapid weight loss. It's like all the signs you would expect there to be a signal, but it doesn't actually lead to the outcome that you would expect, which is, again, why we benefit from these kind of studies and why all three of us get in arguments on threads all the time because people make arguments based on vibes or observations or just assuming patterns exist, whereas when we actually control the data to account for our own flawed assumptions and tendency to draw patterns where none might exist, we actually can get to the truth of the matter.

56:13So pancreatitis ends up being something that I don't tend to like routinely counsel on because what are you going to do aside from, well, I already advised that you probably shouldn't be drinking very much. We're advising weight loss regardless here. And so there's a risk of gallstone development with rapid weight loss, no matter how we go about it. And that's something that we can, you know, be attentive to and intervene on if we need to. So that's just an interesting aspect of the data that, you know, all the things that you might observe or anecdotally hear or expect based on some of these things don't actually tend to pan out the way that we thought.

56:44Yeah. And just lastly, before we get into some of the body composition and performance stuff, Dr. Nadolsky, there's been some concern about this non-arteritic anterior ischemic optic neuropathy or NAION, this irreversible eye condition causes partial or complete vision loss in one or both eyes. Isn't there a major lawsuit against Novo Nordisk right now, like for that? You know, you see that all over the place. There's a$2 billion lawsuit against the manufacturers because these drugs who they don't want you to know, they're taking your vision. Is there any merit to that? Yeah. Notice it's not against Eli Lilly.

57:18I'm kidding. Someone from those departments, they're going to come get me. I'm actually friends with a lot of those people. And they're always switching teams all the time, so it doesn't really matter. But it is true. There are some lawsuits out there. It's a rare risk. We had my buddy, an ophthalmologist retinal specialist on. There was a JAMA article last year that looked at a group of people on semaglutide with type 2 diabetes that showed maybe a small, maybe one in like 10 ,000 people, increased risk of people on the medicine, maybe an increased risk of this type of blindness. But then more recently this year in Journal of Ophthalmology, they showed maybe a trend towards a decreased risk, at least not statistically significant, just no statistical significant risk compared to people not taking the medicine in a similar population.

58:15So if it is a risk, and what my friend told me is that we see it from people's blood pressure going down and usually in the middle of the night, I could see it where the medicine, it's just so powerful and people are still on their blood pressure medicine. They may have sleep apnea where they're going apneic and not getting as much blood flow and oxygen into their blood. Maybe there's some sort of risk there, but the most recent data doesn't show the signal. If it is there, it's extremely rare. It hasn't been seen in any of the weight loss data. It's only in these patients with type 2 diabetes where maybe there's an increased risk anyway.

58:54I'm not super concerned, but patients are concerned. I wouldn't want to go blind. So we try to talk about these, you know, try to talk about the data. I would just say, look, the signal's not there in the most recent analysis. It's in semaglutide only, and those with type 2 diabetes. Potentially, maybe there's some plausibility there, but I would just, if it's there, it's extremely rare. Yeah. All right. I feel satisfied there. We can now move on to some of the other risks and potential side effects that would maybe be pertinent to our listenership, listenership because we're talking about gains, talking about body composition and performance.

59:28So Austin, you know, a lot of people talk about the potential risk of losing all of your muscle when you go on these agents, you know, maybe speak more broadly about, well, look, why is losing lean body mass a problem with weight loss in general? And then what is the long-term consequence of that, you know, for health and performance? Yeah, before we get into that, I do think it's worth pointing out because a lot of these terms can get conflated and definitions can get baked into one another in ways where one audience might hear and interpret this term lean body mass in one way where it's not necessarily being intended in that exact way.

1:00:03Body composition science is complicated. And I know Spencer will get into this a little bit as well. But what does lean body mass mean? What does fat-free mass mean? What does muscle mass mean? You know, all these things have very specific definitions. And so it's important to be clear on what you're talking about. So the haters, as Spencer described them earlier, use this kind of terminology, and they seem to imply that these drugs have a unique effect on reducing or impairing your muscle mass in particular, potentially baking in bone into that as well. And that's a strong claim that would require direct evidence showing that when these medicines are used, that there is a substantially greater degree of specifically muscle mass and or bone mass compared with equivalent amounts of weight loss by other means.

1:00:56When we look at this, we'll get into the specifics of what's observed, but it is a valid concern, just to address your question directly, that if people are losing significant amounts of muscle mass and bone mass, yeah, I would have some concerns about that. I see the end stages of frailty, cachexia, people who have severe sarcopenia, osteopenia, osteoporosis, people who fall, they lose their physical independence, they have fractures, they need to go to nursing homes, things like that. I've been seeing that my entire medical career so far in the hospital setting. And it's not like I have seen, for example, over the course of the past decade, oh, gosh, I'm admitting these people left and right for GLP-1-induced osteosarcopenia, and they're all needing to go to nursing homes because they can't stand up out of a chair anymore, right?

1:01:42And so that's kind of where a strong claim is going to need some strong evidence to support it, or, you know, we need to look at it more directly. So those are some of the reasons why we care about lean body mass is that risk of long-term musculoskeletal health, physical function, independence, things like that. And so that would be the question is, do we see higher rates of those things specifically being impaired from the use of these medicines compared with if you lost 15%, 20%, 25%, whatever amount of weight loss through diet or through metabolic bariatric surgery? Do you see that more? Do you see it less?

1:02:10Does it seem to be about the same? Are there ways, if it's a real thing, can we mitigate it? And what exactly are we talking about? Is it muscle? Is it bone? Is it just lean body mass, which includes body water, all sorts of other tissue compartments and things like that, organ mass, stuff like that? So that's kind of my broad take on it. Yeah. Yeah. Just to summarize for the listenership, the claim is, you know, by again, the haters is that these particular drugs, anti-obesity medications at large, have a unique effect on the skeletal muscle tissue that results in more proportional muscle loss per unit weight loss.

1:02:50and what's widely quoted in literature for just like diet-induced weight loss is that about 75 % of the weight you lose is going to be fat mass and 25 % is going to be not fat mass. And some of that is going to be actual skeletal muscle fibers, but to Austin's point, some of it's just going to be other things that aren't muscle but are also not fat. And so literature then would show you that per pound people lose when they take these medications that more than 25 % would be not fat mass that people were losing. So the question to you, Dr. Nadolsky is, what do you think about the actual risk of losing skeletal muscle mass in relationship to this drugs?

1:03:30I mean, again, there's been a problem that's been a lot of concern over this on social media, especially in the fitness space. Is this a real risk? Like, is that, is this real? Yeah. Some history around it really is, is the Peter Tia, which my brother and I call our podcast, the Peter Tia Hater podcast in, in not because he's, he's generally okay. It's just some hyperbolic statements. He was on the Megan Kelly show a couple of years ago and said that, you know, his patient got fatter, quote, fatter on this medicine. They lost more muscle than they did fat. It's kind of interesting, nice anecdote there.

1:04:05But then he has pulled up that the, um, the step trials, there was a subgroup analysis, they did a subgroup DEXA of some of these patients that use semaglutide in the step trials, which was the obesity trials with semaglutide, high dose semaglutide. And it looked like somewhere around 38 or 39 % fat-free mass loss. So it's kind of like, well, that is more than we'd expect. But Dr. Brockie said fat-free mass loss isn't necessarily muscle. So when you look at a DEXA scan, and this is why I have Chief Science Officer Grant Tinsley, he's literally a body composition expert. He would talk circles around me in terms of how to look at these different compartment models where they look at body composition because a DEXA scan, like, oh, yeah, you got your body fat percentage there, but it's because it looks at fat-free mass and fat mass.

1:05:00And so, like, pretty much everything that's not fat mass, it's like, oh, they lost this much fat-free mass. But a lot of that includes glycogen. Because the interesting thing when they did the same subgroup analysis in the in the surmount data the terzapintide data it was around 25 so a stronger drug that law that resulted in more weight loss actually resulted in about what we would expect amount of fat-free mass loss which we assume if we're just making assumptions has a similar composition of that fat-free mass loss with with muscle so similar to what we'd see with just dieting alone or bariatric surgery alone.

1:05:37So then the claim would have to be something about semaglutide specifically is extra catabolic beyond its ability to help people lose weight beyond this calorie deficit. And there's nothing biologically plausible to make that accurate. What I personally think is that there's some sort of fluid shift because of the GLP-1 receptors. Dr. Baraki talked about the kidneys in the flow trial. I don't know if there's some diuresis effect, there's some fluid shifting, but it's very possible what looks like an increased fat-free mass loss is literally glycogen or fluid changes. That's what I think, because otherwise it doesn't really make sense.

1:06:18Now, having said that, we are doing studies in our online clinic. So we partnered with Dexafit. Dr. Tinsley is doing all this where he actually looks at lean soft tissue. So trying to nail it down to closer to the muscle tissue. And we did a case series, but we have a whole cohort going on. We don't have the data from that yet. And it looks like if you just lift some weights, and we're not talking about like barbell medicine style, you're freaking obsessed with it. Even if you're just kind of like doing like basic two days a week of like what would be recommended and eating sufficient amounts of protein.

1:07:00You're not loading up your each plate with protein and eating, you know, a gram per pound of body weight. We're talking like 1 to 1.2 grams per kilogram of body weight, even somewhere around there with just a couple to two to three days a week of resistance trading full body or splits. you pretty much mitigate it all or minimize it all. So I'm not worried. I think it's good that it's brought this whole thing to the forefront, but I think the whole concern is overblown, and I think it's just a reason for what we call weight stigma, where it's like, no, we don't want people to lose weight. They reduce their risk of heart attacks.

1:07:39They have less liver disease and kidney disease and fewer strokes, but, oh, my God, they lost some extra fat-free mass in there, so watch out. These drugs are bad. I think it's just people are looking for a smoking gun to say, so you can't get out of the hard work. And that's my, that's my, probably my biased opinion. But just from a clinical standpoint, I'm not concerned. I want people to lift weights and eat protein. But like, I'm not concerned if like they don't and they lose this amount of fat-free mass percentage wise. Yeah, yeah. Two additional points. If you actually look at that subgroup analysis in the STEP trial and you look at the placebo group who was just doing lifestyle stuff alone, they also lost more proportional lean mass than you'd expect.

1:08:22So to me, it almost is like perhaps there's an artifact of the measurement technique. At least that's a possibility. But even the latest trial, the semilene study where they had folks on max dose semaglutide and then they did DEXA scans on all these people, it wasn't 75-25. It was 80-20. I was like, ooh, that's interesting. Is there a muscle preservation effect perhaps even? And there's some animal models to support that. I don't think that's true to me. That seems like within the realm of like what's expected. But I just find these concerns about losing so much muscle mass that now you have sarcopenia because of reduced muscle function from all that muscle loss due to these medications.

1:09:03That seems like an overblown risk compared to the potential benefits everywhere else across the board. Yes, if you have somebody where you have concerns about frailty initially, they're probably not a great candidate for a GLP-1 or other anti-obesity medication. although that does get a little more tricky when you talk about like sarcopenic obesity because that was also assessed in the semilene study where they you know 49 percent of the starting population had sarcopenia as diagnosed by I think it was hand grip strength and the appendicular skeletal muscle mass and then at the end of the year only 33 percent had it so it seemed like even though they lost maybe some lean mass their actual function or muscle quality improved.

1:09:44So I don't know, it seems pretty interesting to me. Yeah, this is just not fundamentally a major concern that I have. I agree with Spencer's take in general, and just look at the major outcomes that we care about. And if somebody says, well, the outcome that I care about is my lean mass, and I don't actually care about cardiovascular risk and kidney risk and fatty liver risk and diabetes risk, and I'm unconcerned with the amount of fat mass the person carries. This is my myopic focus is just on lean mass. Okay, don't take the drug. Like nobody's forcing me to take it. But every other area of health and like what we'll call hard outcomes, things that we really care about the most seem to be benefited.

1:10:21And if we were seeing, you know, because we know that sarcopenia, for example, and osteopenia and osteoporosis, they increase the risk of certain things. And so if those risks panned out, we would expect to see those signals in the data. I would expect to see, oh, gosh, we're seeing way more hip fractures in these patients or we're seeing way more falls or we're seeing, you know, all sorts. And if that doesn't show up, then this remains in the realm of hypothesis, but not something that's going to impact my clinical decision making. So, yeah, I agree. It doesn't take a ton of training and it doesn't actually take a ton of protein to, you know, mitigate lean mass loss to the extent it's going to happen here, especially in undertrained or insufficiently active people at the start.

1:11:00And the training is the thing that I emphasize even more than the protein. Like if somebody is willing to do a bit of exercise, I am going to put even not that I'm going to put less emphasis on protein, but it's not my like major lever that I care about. Getting people active in general, not just for the lean mass, but for all sorts of other health benefits is my like strongest, heaviest emphasis for people and always has been even before these drugs ever existed. Yeah. If you looked at like an equalizer, like you got a seven band equalizer and these are all the variables that affect like the proportion of mass compartments that are lost.

1:11:34And so you have things like sleep, you have protein intake, you have these medication use, whatever. All well and good, all can certainly affect that. But exercise, specifically resistance training, is the volume knob. like that that is the main controller here and so without resistance training uh you know all these other things are so the effects are so much smaller and so you know eventually we're going to get a study uh where people are using these agents and actually lifting weights like no shit they're actually lifting lifting weights uh and then we're gonna see the results i i suspect they'll be very positive and then at that point we should follow up with the tia with some other folks who express strong concerns about this and be like, what now?

1:12:19There's a study that's, it's, um, they presented it. It's not published. It's called the T-Rex study. So funny story with my brother and I, with, uh, Brad Schoenfeld, if you know who that is, went to Lily again, I'm like, come on, I'm the biggest Lily, Lily lover. But they, uh, decided to go with a different, um, study team. Apparently they probably, probably a good choice. They're like, who the hell is this guy on podcast? He doesn't know what the hell he's doing, but they chose a different team. They showed it. I saw the slides from the conference where they showed a decrease compared to, I believe, the standard of care group, a decrease in fat-free mass loss.

1:12:57So as we'd expect. And so it was pretty. They cut it in half. And that's kind of what I'm seeing. I'm seeing cutting in half versus like none at all when people are lifting weights. So pretty cool. Yeah. So, again, what I'm hearing you say is that if you take terzepatide, put creatine plus resistance training and a little bit of TRT, it's basically a PED cocktail. Is that what we're talking about here? Yeah. I mean, I'm sure. Have you talked about all the myostatin inhibitors yet on the podcast? I mean, they're studying it. The thing is, it might be overblown. Like, of course, barbell medicine, you know, I'm obsessed with muscle and that type of thing.

1:13:33Is it possible that we're overstating the benefit? We don't want people to get frail, but like, is it possible that we're overemphasizing it? I don't know. We'll see. Because if people live longer and live better with these myostatin inhibitor drugs, then everybody's going to be jacked, ripped, and just like, it's going to be an interesting time. I don't know. Yeah, you just walk around. And at that point, we will have to reject BMI. There'll just be too many jacked people just walking around. And we're like, all right, well, we need another scale here. Yeah, like forget BMI. I mean, yeah, it's actually, that was a big part of the conference and not another tangent.

1:14:06but like going way past the BMI at this point, I'm sure you've talked about this, but we know that the BMI is actually, it does a decent job where not everybody's a NFL linebacker. Most people are not on NFL linebacker walking into the, into the clinic. Not everybody's Jordan and Austin walking into the clinic. And if they were, I would look at them and be like, who cares what their BMI is. Somebody should do that, but pretty cool that we are looking at body composition. I think it's important. Yeah. All right. Well, let's wrap this up with maybe one of the more controversial parts of this podcast.

1:14:40We save it for last because if people tuned out, then they won't send us hate mail. How hard is it to get these medications? You know, we've got some new government policies potentially coming down the pike. It's going to make these more accessible. But to you, Spencer, what is the biggest hurdle for people to, like, gain access and maintain access to these sort of medications? Yeah, it's costs. The costs are ridiculous. You see it over here in the United States. There's these middlemen, these pharmacy benefit managers, and because of rebates and the way they structure it with the manufacturers and go to the insurances and the pharmacies, instead of being like$500,$600 net price, they see this list price of$1 ,200 at the pharmacy.

1:15:2120 % to 30 % of commercial insurances approve it. Actually, it's probably going to go down here because of the cost of these medicines. So that is probably the biggest thing we see. We're going to see that improved over this next few years, though. They just announced lowering the prices. If you go directly with the manufacturer, there's some new prices with Medicare that we weren't seeing before that just were announced. So price, by far price. It used to be, well, price and then access. There's a lot of weight stigma. But now everybody's asking about them. Primary care doctors are feeling more comfortable with them.

1:15:56So like they're, the access isn't as big of a deal with finding a doctor who's comfortable doing it. It's, it's really the cost. And I think it's, I think we're going to see in five to 10 years, just the prices are going to be very low, but it's not so much right now. What's the, what is the role of vineyard? Like what is, how does vineyard fit into, to, to all of this for access and maybe making sure that people are getting the lowest available cost? Is that something that vineyard does? Yeah. So our big thing is like, look, because primary care offices aren't equipped with prior authorization specialists, they don't even, I mean, we get referrals from primary care because they, their back office simply cannot handle the amount of prior authorizations.

1:16:38Everybody knows what that is. You're basically asking insurance permission. Can I write this drug that I recommend for my patient? And they have to jump through these hoops of answering all these questions. They make it tougher and tougher because they don't want to pay. And so I was like, all right, this is one of the biggest pain points. I have to hire a prior authorization specialist to handhold the process of going through that. So that's one thing. Obviously, we're specialists in the field to where we know the dosing better. We know the interactions and how to adjust other medications with losing weight.

1:17:11We're going to focus on resistance training. We have dieticians to minimize side effects and optimize your whole journey. So that's the big thing. We're going to try to get it the lowest cost possible for you, but we're also going to handhold you through the process to make sure your side effects are minimized, your body composition is optimized, and you just have the best time. And you can chat with us online, texting us, as opposed to waiting a whole month to go see your primary care doctor. That suggests it's very quick replies, but also expertise is unparalleled. This is actually a little tangent to that topic about cost.

1:17:50And the way I view it and the way I kind of explain it is that you have these not only brand name, but just prescription medications, and those are the highest cost tier. And then you have compounded versions, which you still need a prescription to obtain, but much lower cost. And then you have research chemicals, which are even lower cost and you don't need a prescription for. Sure. How do you kind of view the risk benefit analysis across that continuum? And do you have these conversations regularly with patients because they're like, look, I like what you're saying. I like the benefits, but that cost, that price point is just too much.

1:18:27So is there ever like a scenario where you think of like permissive use? You're like, oh, look, man, I don't love these compounded versions, but I actually think the benefits outweigh the potential risks. Like, yeah, how do you how do you talk about that? Yeah, the problem with the compounded versions is that they haven't been studied for safety or efficacy. Now, if you look at it, you can see Reddit. I've had patients come from the compounded versions. They've lost plenty of weight. But because of the nature of the compounded industry, you'll never have safety data. You can't do an FDA. You can't do a trial because the ethics committee would be like, no, you've got to use an FDA branded version.

1:19:04There's concerns over where they're getting the sourced active pharmaceutical ingredient. And if they're making it in a certain way, that's making immunogenicity, immunogenic material that wasn't detected. It's a lot of different things. And that might be big pharma fear-mongering against the compound version. So I usually just say, look, if you can't afford the FDA-approved versions and you can't get it direct, like it's getting a lot cheaper. now and it's getting similar almost similar cost of the compound it's still more expensive i i i can't personally attest to the safety of the compounded versions i sure as heck can attest to the research grade peptides now the thing is you'll see there'll be some analysis where it's like 99.5 pure it's it would be as pure as a pharmaceutical grade version and then they'll do an analysis on the next batch and there's nothing in it it's it's actually insane so like You would have to verify every single batch that you got.

1:20:04I wouldn't mess around. I would never have a family member mess around with research grade. I wouldn't recommend compounded versions, but I'm in a, if you want to call it a privileged position to where we could get them the FDA approved versions. So I don't get mad at people for going to the compounded versions because of affordability. What I do say is that the pain of that in the next few years, I think it's going to be so, we're going to look back and be like, oh, wow, those are crazy times because the drugs are going to get so much cheaper and you'd be stupid not to get the FDA approved version because they're going to be so much cheaper.

1:20:40Again, we're just going to go through the pain in the next few years, unfortunately, to get there. All right. Final question to Dr. Baraki. We've been talking about semaglutide, terzepatide, and the future. What about older anti-obesity medications? And what about microdosing? Because people talk about that too. So yeah, thoughts on some of these older medications and also microdosing because we want to be fashionable. Yeah, I think the question about older meds fits in nicely with the conversation that you just had around, you know, balancing risks and benefits of, you know, the non FDA approved versions.

1:21:13If you're either going considering a compounded version or you're going like Chinese bathtub level peptide or something like that, because we have at least as much arguably much even more experience with some of the older anti obesity medicines. Now, what are the downsides of them? Many of them are not quite as potent in terms of their efficacy. Some of them come close. But the upside is that in general, they are way cheaper. They have maybe some of their own inconveniences. I've had plenty of patients, for example, you know, the brand name Qsimia or Phentermine Topiramate is one that is probably the most potent and has the best efficacy among the older ones.

1:21:48It's an oral agent when it comes in the combination form that's branded. It might be a little bit less accessible for some folks, but it's also something that for somebody who's willing to go through with it and deal with a little bit more inconvenience, prescribe the meds separately in generic form, and it can do its thing, potentially as a way to get people through this temporary, ideally, period of discomfort or pain that Spencer described until the cost and the prices come down. So I think they do still have a role for now. They can be used in conjunction with GLP-1s. They can be used on their own.

1:22:19They can be a bridge on or a bridge off. There's all sorts of different creative strategies that we can use when using things like, again, phentermine topiramate. Less favored is going to be bupropion naltrexone, but I've had plenty of patients who've used it with varying levels of success, some who did great, some who didn't do as well, some who didn't get as much of a, who kind of fell somewhere in between, which is going to be the case for most interventions. And then some patients who have very interesting, maybe disproportionate responses to certain things, to phentermine monotherapy, just by itself, which is not something that many of us use too often anymore, but, you know, once in a while, a patient will respond really well to that, or to topiramate, or to some, you know, antidepressant category type medicines that for some patients have appetite modifying type effects and things like that.

1:23:00So bottom line is they do still have a role. They tend to be less expensive. They have their own unique pros and cons that you need somebody who has expertise and experience with them to be able to discuss with the patient and then be able to monitor their therapy and things like that over time. And hopefully to keep kind of poking at this and engaging with this process to see, well, when does the cost benefit become, you know, within reach for you or become accessible? Or do you maybe unfortunately develop a condition that would qualify you for one of these things in a different way? These are all things that we'd be paying attention to.

1:23:29So that's my take on the older meds. And then lastly, the micro dosing topic, that's another thing that you'll see popularly on social media. It's not something that I don't think either of us is going to routinely be recommending for people, mainly because we don't have the quality of evidence behind those strategies for the types of outcomes that we're looking for in terms of be it weight loss, blood sugar control, cardiovascular risk, kidney, liver, all these other sorts of things. I can't say with confidence that using those levels of doses is going to get you those outcomes that you might be interested in.

1:23:58Now, the caveat there is that when you are an independent practicing clinician who feels confident with your, you know, with your practice, because I end up doing this with a lot of other things, you can do stuff off-label all the time if you are comfortable with it, if you have a sense of the potential benefits, the potential risks. You're able to discuss this with your patient. And so where that might come more into play, and probably does more regularly come into play, is dosing for tolerability, right? And so we know that tolerance, the side effect risks that we talked about earlier, the overwhelming majority of it is going to relate to dosage.

1:24:30And so tinkering with dosages is probably the way that we end up dealing with most of the side effect kind of profiles, whether going to, you know, even tinier, tinier doses or and or stretching out that on ramp process to be even longer, you know, a lot of the traditional dosing regimens, it's you go on this dose for four weeks, and then you bump it up from there, etc. I could stretch that out longer if I wanted to, I could keep you on a lower dose for longer or increment you in a small in a smaller way. If you're comfortable with these things, you can use those types of strategies. But it's not going to be a standard recommendation for us at this time until or unless we have better quality data, I'm not going to go out making grandiose claims about if you just micro dose, you'll get these like life-changing benefits with no side effects or risk or something like that.

1:25:12I don't have concerns about risks at the very low doses, and that's why we would use those potentially as a strategy for tolerability, but not really so much outside of that. So that's my take there. Excellent. All right. Well, to sum up, the data's clear. The new anti-obesity medications, especially those targeting multiple receptor pathways, well, they're offering efficacy that rivals metabolic and bariatric surgery with improved tolerability, and they're showing clear benefits for cardiovascular, kidney, and liver health with additional potential in the future. If you'd like to have a discussion with professionals about this, you can click on the link in our description below in the show notes.

1:25:50You can connect with professionals at Vineyard. That's Dr. Dodolsky's company, and Austin will be starting there shortly. So if you want to work with Dr. Baraki there, and it's not just weight loss. Spencer, can you talk about some of the other stuff that you guys deal with. I know you mentioned cardiometabolic health at the onset, but yeah, what can people expect if they end up heading to vineyard? Yeah, so think about obesity, but also obesity adjacent cardiometabolic health, lipids, cholesterol. We also help with things like easy things like hair loss. If you're losing your hair from the weight loss, we can jump in with minoxidil.

1:26:28If you're a guy and you just have androgenic hair loss, we can do a little finasteride. We can't call ourselves primary care. We like to stick to the cardiometabolic, but we can do some of these other things that places, these pill mills that you see where you pay$50 a month. We can send it to places like Mark Cuban if your insurance doesn't cover it. So even skin care like tretinoin. But think about blood pressure, lipid, glycemic control, and weight losses in general and then anything kind of adjacent to that. There you go. And for all your training and nutrition needs, you can check out Barbell Medicine.

1:27:01But before you guys go anywhere, please leave us a five-star rating and review. It really helps drive traffic to our podcast so we can keep bringing you all the latest nuance in health and fitness. A special shout-out to Dr. Nidodolsky and Dr. Baraki for joining me, Dr. Jordan Weigenbaum, on the Barbell Medicine Podcast. We'll catch you next week and every week right here on the Barbell Medicine Podcast.