Longevity / GLP-1s, Heart Health, and the Metabolic Foundation of Longevity - Full Transcript

GLP-1s, Heart Health, and the Metabolic Foundation of Longevity

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Hello everyone and welcome to another LEMD educational series. We're so excited to have you here as we continue our mission to support healthier, longer lives through education, innovation, and of course, community. Tonight, we're thrilled to welcome back Dr. Matt Sager. If you joined us before, you know Dr. Seager is a leading cardiologist and data scientist specializing in improving cardiovascular care. As a cardiac electrphysiologist fellow at Texas Heart Institute, he focuses on using machine learning and AI to develop cuttingedge risk prediction models, especially for diabetes related heart complications. Dr. Sager's impressive background, including a residency at UT Southwestern Medical Center, a medical degree from Indiana University, and even a degree in computer science with a master's in biioinformatics. Wow, you're so impressive. He's passionate about personalized data-driven healthcare solutions that truly make an impact. Dr. Sager, we're so lucky to have you back again. Welcome. How are you doing? I'm doing well. I'm excited to be here. This is a topic that I'm really passionate about. So much is changing. Even talking to you guys a couple months ago, there's a lot of uh new ground to cover. So, I'm excited to get going. Oh, likewise. Well, to start, can you share a little about your journey into cardiology and what inspired you to focus on heart and heart health solutions? You touched on being an electrphysiologist. You're the electrician of the heart. Um, just tell us about your journey a little bit. Yeah, I started in the technology space, was a programmer prior to medical school. got tired of looking at computers all days though wanted to talk to people and really enjoyed medicine and my journey has been very organic and serendipitous in a way and uh I really enjoy the diabetes space it's such a unique condition where there's a lot of

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unique condition where there's a lot of really fun exciting new treatments uh and it's been a really exciting journey and then the interaction between diabetes the heart entire body systems cardioabolic disease as it's called has really been a niche fun area that I've explored and have been able to do a lot of trials initially with SGLT2 inhibitors now kind of moving into the GLP space uh as well. So, a lot of things that we can touch on. I know I mean what I'm so excited about our conversation tonight around all the studies that are coming out and what you've been part of. Um, can you just for for people new to this journey or GLP-1s, can you talk about how GLP-1 medications uh specifically benefit heart health beyond weight loss? Yes. So, let's first take a step back and I think it's important before we start this conversation to talk a little bit about the history of these medicines because by far and away one of the biggest concerns that people bring to me are that these are new medicines. How do we know what is going to be happening? And so I want to first of all to say that these medicines have been around for decades. So the first GLP medicine what came out in about 2004. So we've have over 20 years of established FDA approved GLP-1 medicines that we have seen very long-term side effects. So the first trial started in the 90s. So we have over 30 years of data for these medicines. So why are we talking about it now? Well, at first these medicines were once daily, sometimes multiple times daily injections. Very unpopular in terms of prescribing unless you really really needed it. But we did know that these medicines did help reduce weight loss or help improve weight loss for the last 30 years. It's really just when simaglatide came out that we went from daily injection with loraglletide to weekly injections with simaglletide that this explosion of new information's really

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explosion of new information's really come about. So these medicines have been around for a while. They're incredibly safe, but there's a lot of things that we should talk about. So specifically with the heart, so what we've observed is that GOP1, so glucagon like peptide one is expressed throughout the entire body. You have it on your vessels. You have it in your pancreas. You have it in your GI system. But you also express it on the heart as well in in small quantities. And what you find is that when you act on that receptor in the heart, it has a lot of really favorable benefits. So by and large, what these medicines do is that it helps improve blood pressure. It helps improve heart failure. It helps improve cardiovascular disease meaning dying from a cardiovascular cause that includes stroke, MI, myioardial inffection, heart attacks, uh heart failure and then also just reducing all cause mortality. And what I mean by that is it helps you prevent death from any cause. It helps you live longer and even the trials when they're three and a half, four years, you're seeing upwards of four and a half, five, six months longer longevity in just in that short time frame. So, it's an really impressive medicine and we can get into the nitty-g gritties about where exactly these medicines are working as well, but by and large across the entire spectrum of cardiovascular disease, it helps reduce every single one. Yeah, that's so incredible. And you know, um you were part of the dandelion study you mentioned um uh which was released in 2024. It was seven times larger than NOVA's trial. Um, I think what it determined was that even those without severe dise disease had a 15 to 20% lower risk scores for major adverse cardiac events after taking a GLP1 drug for three years. That's yeah so impressive. Can you talk about that and what else you determined from from that study? Whatever you can share. Um, yeah. So these medicines first came out for the diabetes space. The way they

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the diabetes space. The way they initially were aimed or the mechanism of action is that it helps reduce glucose levels, sugar levels in the body, helps improve insulin sensitivity, makes insulin work a little bit stronger. So that these medicines were initially targeted for people with diabetes. What we've now seen uh with things like the select trial among others is that they work in people without diabetes as well. So the effects in patients with diabetes are incredibly strong. Reducing heart failure, reducing cardiovascular death and just as well in people without diabetes, you see just as strong, if not even stronger signals uh for reducing all the same outcomes. Now what is the the research say about GLP1s reducing the risk of heart attacks and strokes specifically? So the uh the data is pretty impressive. you're looking at about a 20% reduction in what we call nonfatal cardiovascular disease. So, not dying of cardiovascular disease, but the things that still affect you. You still want to prevent strokes, you still want to prevent heart attacks, you still want to prevent being hospitalized with heart failure. And for all three of those, uh, it improves. So, why why is that? And I think it has to do a little bit with the mechanism of action of these medicines. So, on your blood vessels themselves, you have some GLP receptors. when you act upon it, it releases nitric oxide and so that helps vasoddilate, expand those vessels, lowering blood pressure, lowering the stress on the heart. It also helps uh locally with inflammation in that blood vessel as well, help preventing we think plaque formation, which is the contributor to strokes and heart attacks. Wow. I you know, I didn't even realize that you're so with the nitric oxide. Yes. and it dilates the blood vessels. It makes sense. Um can you share a little bit more about nitric oxide for people who are new to the idea or or concept like what does it do in the body? What is it? What purpose does it

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body? What is it? What purpose does it serve? Um and the importance of it. Yeah. So I think people have a really good fundamental understanding of this. They may just not realize it. So, uh, whenever when someone has a heart attack, for example, and they have those little nitro give them like a little nitro paste or little sublingual nitroglycerin, you put it under your tongue to dissolve. It's one of the first things we do in heart attacks. It's the reason why when you take nitric oxide, it vasoddilates. It opens those blood vessels. Um, but it's essentially it's a chemical, a little molecule that is very fast acting. It goes through the body incredibly quickly and then it just latches on to different cells and then helps them kind of think expanded away but relax is probably the better term. So it it you see it in a lot of the vessels around the heart as well as within the heart itself but any sort of blood vessel kind of opens up uh pretty pretty quickly. Yeah. But from what I understand nitric oxide levels decline as we get older. I mean it's a big buzzword in the longevity community right it declines I mean even mouthwash decreases the level of nitric oxide in our body and so right so there's different so nitric oxide's expressed in lots of places uh in the body so within the vessels as a cardiologist I deal with the the vessels but nitric oxide is also found in the gut and other place GI system especially um it's definitely hot area I'm not a GI expert but you're exactly Right. Well, this is really important to know. Thank you for pointing that out. Um, regarding the GLP1s and how it behaves, how it relates to nitric oxide. So, can you talk to us about are GLP1s a game changer for patients with high cholesterol and hypertension? Talk to us about that and why are coming off their statins even as a result of GLP1s. Absolutely. So, I the the reason why

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Absolutely. So, I the the reason why again goes to the mechanism. It always comes back to why these medicines work and then once you understand the the mechanism you can explain all the really amazing benefits for why taking these medicines is so awesome. So GLP is expressed also in the liver which is the major organ responsible for lipid cholesterol metabolism. It essentially helps ramp up the good cholesterol in your ba in your body HDL while helping reduce LDL. uh the specifically that it works on uh different hormones like TNF alpha, TNF beta, cytoine release factor, all those kinds of things that are pro-inflammatory that are also have a important part in lipid metabolism. But throughout the entire spectrum of your lipid profile, you see really impressive benefits uh with these medicines. Some of it can be attributed to weight loss itself. When you have fewer fat molecules in the body, there's uh less likely that you're going to develop those bad cholesterol molecules. But the other part of that equation is it works in the liver directly to help improve your lipid profile as well. And so it's incredibly exciting when you may have you're on the border, your triglycerides are high, your bad cholesterol, your LDL's high, you get on these medicines and then your your ASCBD risk. So in cardiology, we have these amazing risk scores that we use in our guidelines to help dictate or help prescribe statin medicine. So if your risk is above 7. 5, statins recommended, but you're able to see with your lipid profile, your blood pressure, all these other things that get better, your ASCBD risk is lower and you may not need a statin anymore. That is Thank you again. I mean, these are things that you you pick up and you read, but you forget because we have so many patients that get on GLP1 medications and their their hypertension goes down. They're at 165 and it goes

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goes down. They're at 165 and it goes down to normal ranges in a very short period of time. So, you're saying it's not just the weight loss, it's also how it acts on the liver. Wow, guys, are you catching this? This is news to me. So, thank you for sharing that. Um can you talk about how GLP1s improve insulin sensitivity and how they regulate blood sugar levels? Yes. So this is the longest standing uh mechanism or understanding that we have of these medicines. So GLP was first identified in the pancreas. So the pancreas has these different cells alpha cells beta cells that are responsible for insulin sensitivity. So when glucagon or GLP gets activated, it essentially releases insulin and makes it more sensitive to insulin. So if you have these medicines, it essentially makes insulin more sensitive and work more effectively so that you uh in response to food more insulin's released, glucose levels come down uh and the all the benefits that you have are directly responsible because of the improved working of the pancreas. Now how does this affect type 1 diabetics? What? That's an amazingly good question. These medicines have not been studied directly in type 1 diabetes. There's a lot of theories out there of that they they work really really well. I know of a few endocrinologists that are prescribing it with the understanding that you need to have very close monitoring. There's have to have a failed other therapies. The type 1 diabetes space is uh unfortunately not a lot of trials have I literally had somebody a couple months ago ask, "Hey, I you've developed a risk score for type two diabetes. Would you be willing to develop one for type 1 diabetes?" I looked into it. There's just not a lot of data uh in this space. So, it's more we don't know. Not that it may not work, it's just that we don't know and don't have the the population

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know and don't have the the population to test it yet. Now, um a lot of physicians actually disqualify patients if they're type 1 diabetics getting on these medications. Maybe would you as a cardiologist would you disqualify a patient if they were type one or I would just because it's going against the labeling directly. Now there's other reasons why you may want to be on it, but that's it to be a hard conversation and you need to have that a really long conversation specifically with the patient themselves and not just this cart blanch. Yeah, if you have type 1 diabetes, these medicines are okay. It's more of a personal patient physician relationship that you need to establish to determine if it's right for you. Okay. So, let's talk about long-term benefits for type 2 diabetes. Yes. There. What are the benefits? Well, the biggest benefit is you live longer, period. There's very few medicines we have in life where you can say that these medicines improve all cause mortality, dying of any cause. That's such a profound statement when you think about it that these medicines really do help you live longer. Uh it not just helps you live longer, but it helps improve your quality of life and that's so important as well. So we we have a lot of these standardized questionnaires like the Kansas City questionnaire, KCCQ, you have your San Francisco questionnaire. There's there's a bunch of these standardized tests that if you're in a clinical trial, it helps keep things protocolized. And across the spectrum, people just feel better across symptom relief, uh improving their activities of daily living, uh mobility, joint pain. It's just it's a really impressive spectrum that these medicines work. I can't say good enough good things from a symptom and quality standpoint. Okay. So as you know the recommendations a BMI of 27 and greater with a coorbidity 31 and above. Um so we

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with a coorbidity 31 and above. Um so we offer the micro dose version of it and there's a lot of growing evidence around micro doing GLP1s and all these benefits people are experiencing. Can you touch on micro dosing and what you're seeing and what you're reading and it's so incredible because 2 three years ago when we you know started in the compounding GLP1 space there weren't a lot of research and studies coming out around it. Now when you search research it's like within a minute I could come across 10 longevity studies around GL. So what are you reading? What are you seeing? Can you talk to us about micro doing? Yes. So the clinical trial data we have is on the the very specified you start at 0. 5 trying to go up to you know one 1. 4 2. 4 etc. But regardless of the amount that you're on, t taking some can be is more beneficial than not taking any. So even anything that you can tolerate has benefits. U the higher the dose a lot of times you get a little bit better efficacy from a cardiovascular major adverse cardiovascular event standpoint, but you still do see results even from very small doses. And the better part about that is that symptoms the the a lot of the symptoms side effects that you see are not as prevalent much lower doses. Um the studies that you're talking about are uh still coming out. I think there's some really exciting trials coming out in the space on much smaller doses. A lot of the data that we have right now is more in observational studies. Uh but nonetheless, they've all been the same signal of these medicines work. Some is better than none. Whatever you can take is beneficial. Keep doing what you're doing. Essentially, I mean, we're seeing it with so many people where their brain fog goes away and they just feel better and they feel energized and on micro dose levels, right? Yes. So, let me This

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dose levels, right? Yes. So, let me This was a really exciting the last literally two months that you and I talked last the reason the brain fog. It's so funny you say that there was a it was a park it was a a really small like less than 50 patient but it was a randomized study for dementia and um other psychological brain disorders and what they observed similar when we were talking about nitric oxide on helping vasoddilate the same thing was seen in the arteries of the brain specifically in the hippocampus. So that brain fog that you exactly alluded to was one of the major symptoms that uh or side effects that went away in in this study. So you hit the nail on the head right there and we hypothesize it's because of the arteries opening up in the hippocample region of the brain. Okay, we'll talk about hormones in a little bit, but I I want to touch on this um you know the brain and how it functions and mood disorders too. There's growing evidence that GLP-1s affect mood mood. How do they impact anxiety and depression from what you're studying and reading? So, depression uh is probably the biggest unknown right now. I I've I've looked into this extensively and I keep getting conflicting information and I think some of it is because of confounding and what I mean by that. So, let's take a step back. So anti-depressants, your SSRIs, your normal fluoxitine, like your normal medicines, they still have a blackbox warning that these increase rates of depression even though you're taking it for depression. And that's because these medicines give you a little bit make you feel a little bit better and that you may have more energy to have suicidal ideation. Regardless, I think we're seeing the same thing in GLPs where people feel better, so they have a little bit more energy, so they're more likely to act on if they have an underlying depressive disorder that's not being treated appropriately, they may uh then have the

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appropriately, they may uh then have the energy levels to take drastic action. The correlary of that is that GLPS have been shown to reduce depression by a pretty good amount. I think there's so much we don't understand about the brain and it re works really really well in some people and then in some people that's there's something that we're missing. There's something untreated that they're not being compensated for that when we give these medicines it's not the medicine necessarily. It's something else being activated that's um making them worse mentally. But I think by and large the consensus is these medicines really do help with depression and then absolutely they help with anxiety. I think that's that's there's not a lot of uh dispute in that area uh that there are activity levels go up your concentration and like we were talking about the brain fog going away is such a positive benefit that's been very well studied now. Yeah. And we're seeing it with our patient population too where you're getting the spectrum. Some people are like, "My depression has completely improved. I'm doing amazing." And some people are like, "No, I'm I'm feeling something. I'm feeling a little bit of funk." Um, and I don't know if it's um drug specific where where you know, tears appetite for example, it's a GLP1 GIP. It does work on dopamine. I do want to talk about addiction and how how it affects um the reward pathways, but you know, could it be that the way that it works on the reward pathways? Well, if it inhibits that in any sort of way, well, if you you're more susceptible to dopamine receptor like depression, depressive episodes, right? Um yeah, would it affect you? Would it uh would it cause greater depression? I don't know. I mean I'm reading conflicting information as well and I'm it is it's a little conflicting. One of the newer studies I think this came out in January was uh looking at Parkinson's disease. So Parkinson's disease is typically a

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So Parkinson's disease is typically a disorder of dopamine. You have lack of dopamine. The way we treat Parkinson's is giving essentially endogenous dopamine in different forms to help keep the levels higher in the brain. And when giving GLPS, they found that the one of the proteins alpha sinuclean specifically was uh more reduced in patients that took simaglletide compared to those that did not. And they did that by imaging the brain with uh PET imaging. And this was I think a six-month trial. Uh so there's something happening in the brain. There's so much we don't understand. But a lot of what we're seeing is positive. And if you have another avenue to treat things like Parkinson's, Alzheimer's, that'd be such an incredible um medical achievement in a way. Yeah. So, let's talk about that. Let's talk about addiction, how they're Yes. drugs to to help with addiction and so forth. So, maybe you could share a little about the studies that are coming out recently. Yes. Very recently came out after you and I talked last. So, this uh Jamama Psychiatry, incredibly respectable journal. So this was 48 patients. So they call it a phase two trial, but it was still a randomized trial. They took patients that uh were had alcohol use disorder, had problems with alcohol, randomized them to GLP versus placebo. And they saw again really profound decreases in alcohol use dependence uh in patients that took GLP-1s. And they actually were able to quantify it both from craving standpoint and the number of drinks that people drank per day. So by definition in the medical society, two drinks a day for a woman is considered alcohol use disorder. So if you're reducing that by over a drink, having one a day that you're getting patients that had alcohol use to essentially more or less normal alcohol use levels. So really impressive results from a medicine over the course of this was not very long, four months

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of this was not very long, four months or something pretty short. Uh pretty nice exciting information. Yeah. What do you hypothesize is happening in the brain? What is causing this? Yeah, that's such a great question. I think there's a lot of overlap with uh food hunger, food craving, food noise, and the reward pathways in the brain. There's a lot of overlap with substance abuse whether it's alcohol or other drugs and food. Food is a can be considered a drug. It's something indogenous that you're have a craving for. Uh and GLP is expressed very very highly in the uh reward pathways at the brain. So you think of the front of the bane brain as more cognitive thinking, higher level thinking. Back in the brain is more your primitive the things that you need to survive. While the GLPs work in the back part of your brain, the thing the things that essentially make humans human, the the things that we need to survive, the the basics of living and uh the fact that it improves food craving and alcohol use, I think is is kind of a no-brainer and makes a lot of sense. Yeah, that that to me is so interesting because I mean there's studies coming out with smoking addiction as well. It's not just uh related to alcohol. We're hearing shopping addiction, smoking addiction. But what's interesting is it doesn't take away all the reward, right? Like people don't don't lose their desire to work out and exercise or um I don't know. It's just interesting how it's working. It is absolutely. Yeah. So, um can you talk to us about the GLP1's effect on gut microbiome and gut microbiome health? Yes. First off, this is such an difficult unexplored area just as a science in of itself. So the body of evidence we have in the gut microbiome, I think is such a ripe opportunity for

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I think is such a ripe opportunity for future research. Uh we do know that a lot of what we can hypothesize is that there are a lot of changes in the gut microbiome. We just don't know how that relates to the mechanism or the the benefits that we see. So we know that there are changes but we don't know if those changes are what's contributing to the improvements in cardiovascular disease for example or if it's a byproduct of something else that's happening. So we talked about nitric oxide that nitric oxides expressed in blood vessels heart but it's also found in the gut. A lot of the nutrients that bacteria and microbiome use in the b in the GI system are affected when sugar levels are changed. So a lot of times some of the bad microbiome, gut hormone or gut pathogens are reduced. They kind of die out while you have this flourishing of things that can be seen as more favorable. Uh the mechanisms and what that means, like I said, is still a little bit unexplored. Um but I'm really excited and encouraged to see kind of what comes out in the future. Yeah. Well, I mean it it kind of makes sense when you have less sugar cravings, right? You're eating less. You don't have the same cravings that you did. You give your body that rest, the gut microbiome of rest. And also candida, right? Yeast and bacteria compete for resources. So, you kind of your body goes into a state of homeostasis. I mean, it makes sense to me. Um can you talk to us about these medications impact on digestive disorders like IBS, GIRD or leaky gut? Yes. So the biggest side effects that you see in these medicines are directly because of a mechanism of action. So GLP acts on the stomach to slow gastric emptying. So the the food stays in your stomach longer. you can expect that

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stomach longer. you can expect that you're going to have things like nausea, some indigestion, uh, and then you some people get constipation, some people get diarrhea. It's impossible for me to predict. I tell people to be on the lookout for both, and if you have it, then we can treat it. So, the the nausea tends a lot of these side effects tend to go away with time. They're horrible in the first probably I usually say three weeks. A lot of time immediately after taking the medicine they so they're once weekly medicines. The first three to four days after the injection can be bad. After your second injection usually two to three days after your third injection a day or two and then you're usually good after that third inject injection. The heartburn can be noticeable those first that first month or so just because your body is getting used to more food in your stomach and trying to figure out how to empty the stomach. And like I said, the nausea tends to go away after that same time frame. Uh leaky gut, I think, is such an unexplored area and not my area of expertise. I'm probably the as a cardiologist, I may be the wrong person to ask. Um I I don't know much about that particularly. What I've seen looks favorable. I just personally can't explain the mechanism for for why it's happening. I uh I just know that it's it it would be something this medicine would be something I would consider if a patient came to me and said, "Hey, I have leaky gutter. Hey, I think I have this." This would be a medicine that I would not hesitate to try. Yeah. So going back to the cardiovascular benefits of these medications now at a micro dose level and I'm saying less than 0. 25 25 milligrams for example for semiglutide or 2. 5 for tepatide. Um do what would would you still reap the cardiovascular health benefits at very low doses even half of that right? Would you still reap the benefits? I yes to you you'd still have benefits

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I yes to you you'd still have benefits absolutely so if you're talking about would would I benefit from being on this medicines? Yes. Is the benefit additive on higher doses? Probably, but it's hard to say entirely. Uh, a lot of times you need these receptors to be saturated in some effect so that the the levels have to take time to build up. So, I imagine from from a micro doing standpoint, if you take it for a longer period of time, then the the levels have time to build up in your body and exert their favorable effects. Now, a lot of the things that you'll have effect from may be a little take a little bit longer. So, for example, in these trials, you lose roughly 15% of your body weight in the first six months. It may take a little bit longer, but if you can still lose body weight and you have a better lipid profile and lab profile and all these other things, then yeah, a lot of the cardiovascular benefits are independent of just the medicine medicine themselves, but all the other uh positives that your body's going through as well. So I'm 2. 5 of tresepatite is I'm that's a great dose. Uh the less than 0. 25 of simaglletide is a little bit less studied but it's I can I would not hesitate to if somebody's like hey that's what I want to try please by all means let's do that. I'm excited for you. Okay, on that topic, are you seeing differences in the two population groups that are using simaglletide versus turepide? What are the studies saying about the two groups? Yeah. So, we have one head-to - head study from a weight loss standpoint on tzepide versus simaglletide. And tzepide just because it has that extra hormone, it's GLP in addition to GIP. Uh, you see instead of a 10% or so weight loss with simaglletide, you see about 15% or more with tzepide. The cardiovascular

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with tzepide. The cardiovascular benefits are very similar. Uh, from a weight loss standpoint really is where you see the biggest benefit. Okay. Um, now if you were to give a patient a recommendation of which medication to go on, which one would you recommend to them? Um, what what why would you put them on the other medication perhaps? Uh, I think it it has to do with what their goals are. So if they're if they came to me and is like, I want to reduce the I want to lose the most amount of weight that I can, I think it's a no-brainer. Tzepide very clearly shown to help reduce weight the most. If cost was the biggest issue, simaglatide tends to be a little bit cheaper than trespathide. uh if they're talking about the A1C benefits, I want to help control my sugars a little bit more than Tzepide lowers your A1C a little bit better than simaglletide. But if they're talking about I just want cardiovascular risk benefits. Well, simaglletide is the only one right now that's truly proven by the FDA to reduce cardiovascular benefits. Uh and it tends to be a little bit easier to take. there's a little bit less side effects with synagoguatide than that I've seen within treseptide. So I think it's a great uh first medicine. Okay. So talking about the future of these medications and their evolution. So now we have rea that that has come out. So what do you think about that? We have rea coming out and where is this going? Where what's the future looking like? Oh my gosh, we could talk for an hour on these medicines. We want to know. Yeah. The the there's so much coming out. So the the kidney disease data is amazing. The uh there's a poststroke study that's coming out. There's some Alzheimer's disease dementia studies. There's a lot more muscle preservation studies. I think it's the kagrama excuse me. So like

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the kagrama excuse me. So like simaglatide, tzepide, kagrin, kagrinitide. There's so many of these medicines. There's oral formulations that are coming out, long acting oral formulations. Uh there's twice yearly long acting injectables, which would be incredible. Um and then there's medicines like the GLPs mixed with other things like amalin analoges. So amalin's been around for decades, but just like the lauragotide story, it's a three times daily injection for people that have pancreatic disorder that don't produce certain pancreas hormones, but we're getting into the once weekly amalin analoges as well. My uh research mentor at UT Southwestern just published literally last week a metabolic accelerator called HU6. It's not doesn't even have a full name yet. This was in JAMAMA cardiology. uh did incredibly well at weight loss, completely different mechanism, but didn't have the uh the nausea GI side effects and it was really impressive. So, like I said, there's so much coming out in this space and so much exciting new information. I guarantee you we talk again in two months, this will be a completely different conversation. No, absolutely. So uh obviously with any sort of weight loss, muscle loss is is almost uh unavoidable. Um so are there recommendations you would give patients who are on these medications uh altogether? Like would you couple this this medication with something else? like sometimes we couple it with samoralin to help preserve muscle and help with um fat loss. But what would you recommend if you're getting on these medications for the first time? Yeah, so the we studied the luraglletide. We we got MRIs of the thigh and belly. So we looked at central atyposity that fat around the belly as well as fat within

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around the belly as well as fat within the thigh muscle itself. And we did this over the course of six months in longitudinal MRI studies. And we published this in the journal of sarcopenia and showed that the amount of fat that you lose in the muscle itself is pretty profound. But some people about half also lost some muscle mass. So we went back and looked at this and a lot of it was because they weren't getting the daily nutrients that they would normally get on a when they were eating more. So when you feel nauseated, you just stop eating. It doesn't matter the mechanism of of losing weight in anything. If you stop eating, you're going to lose muscle mass. So, the biggest thing that I say is still try to get your daily nutrients of your protein, carbohydrates, fats, healthy fats, and then water intake especially because kidney stones is another thing that we're starting to see because people just stop drinking water and it's not a really good sign. the the Sormalin is a really hot interesting idea. I if somebody came to me and asked if they should be on it, then I I would not discourage it. Uh I just don't know enough from a research standpoint to to fully recommend it without them doing their own research as well. Uh but it it mechanistically it makes sense to me. I just don't think that there's been enough studies in that space directly. But weight training, getting your normal aerobic exercise, anorobic exercise with lifting weights, making sure you're still trying to maintain the mass that you have is by far the the best treatment when you're getting on these medicines. That's wonderful. And guys, if you have questions for Dr. Sager, especially, I mean, he's a remarkable cardiologist. So, if you have any questions, please post it in the the chat section and we'll get to it. But Dr. Sager, what

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we'll get to it. But Dr. Sager, what else do you would you say around these medications and longevity? I What's the consensus where you recommend this obviously, but is there anything you'd like to add and tell us? Yeah, let's talk uh let's talk about something we haven't talked about at all, and that's um PCOS. So, I am very hopeful in the short future that the FDA will recommend this for PCOS directly. And this is because of a couple really profound studies that have come out on looking at actual ovarian follical changes on these medicines. So you get differences in androgen sensitivities uh with these medicines that help improve PCOS symptoms and the the disease that is PCOS. And that's not to even take into consideration the weight loss effects, the improvements in estrogen handling and other hormones that are um independent of these medicines as well. So I'm very hopeful in the short future that PCOS will be one of the approved treatment reasons for these medicines. Yeah, that's interesting you say that. I just recently last week met someone. She was very healthy, an athlete. Um but but she wasn't your when you think of PCOS like that was not you know she's not someone that you would think of and her doctors at 18 put her on these medications and it has completely changed her life. So she was so excited to share this with as many people and so we also have the sleep apnnea it's been approved for sleep apnea first see anything else that these medications will get approved for. Do you think one day it'll be a front group for Alzheimer's and dementia? What else do you see in the near? Yeah, absolutely. Alzheimer's, dementia, osteoporosis is another big one and again goes to the mechanism. So I always remember from medical school osteoblast build bone. I still remember that from my histo slides and GLP is expressed on osteoblasts. It's very cool. So these medicines help build bone and help uh keep the strength

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build bone and help uh keep the strength of the bone in check and it helps prevent osteoclasts which help break down bone from functioning. So it has both effects. It helps build bone and it helps prevent the bone degradation from happening. So another really exciting mechanism I think in the future. Uh pediatric diseases there's other types of heart failure in the cardiology space. So there's two types of heart failure. There's heart failure where your heart doesn't squeeze as well. We call that FEF or heart failure with reduced ejection fraction. There's also FF, heart failure with preserved ejection fraction. That's where your heart gets a little bit stiff, doesn't relax, it doesn't open up as easily. Uh it's a medicine will absolutely work in this population. We're already seeing it before the trials have come out and that's because these medicines work by helping muscles repair themselves, reducing fat. When you reduce the fat, the muscle can stretch a little bit more, relax that nitric oxide like we talked about. Uh the heart failure symptoms kind of go away. It's so yes, so many things we can talk about that are still continuing to be explored. I'm I'm getting some questions coming in, so throw some out. Uh what can I pair my tears with to help with my CAD? The CAD meaning coronary artery disease. Is that what we're saying? Um, it So, that's a good question. It depends the level of coronary artery disease that you have. So, if you're somebody that has a stent already, then you need something to help thin the blood. These medicines don't really help with blood thinning. So, you'd still need your aspirin. If you've had a stent in the last 12 months, then you need two antiplatlet agents. Uh, as of now, the guidelines still recommend a statin. Not because they want to reduce chole your cholesterol levels may be really low. Uh but there's something about having a stent in your heart where the cholesterol gets a little bit sticky in that you still develop these plaques

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in that you still develop these plaques and statins still do help prevent those plaque formations in stented areas. Uh but if you're somebody that just has we call non-obstructive coronary artery disease, then uh there's not much you really need to be on uh besides making sure your cholesterol levels are in check less than 70 and then an aspirin is a very hit or miss question on uh whether it's recommended. There's a lot of data that you don't even need an aspirin anymore. So it's a good question for your cardiologist as well. Um, Angel asks, "What would you recommend for COPD and emphyma?" So, there's obstructive sleep apnea is one of the, as you alluded to, one of the indications to be on GLP-1 medicines and a lot of times it helps decrease that neck circumference so that your glauus doesn't drop and obstruct your airway during sleep. Uh, so by and of itself, GLP1s are an appropriate treatment. Now, if you're having if you're not responsive or you're having other obstructive disorders, then a CPAP and seeing a sleep specialist is AB is paramount. There's a lot of really cool things now in sleep apnnea where they can have essentially use electricity to help keep your glauus open and when you sleep. Uh so you don't need to even wear a CPAP and those are put in by usually ear nose and throat doctors. Um, but from a GLP one medicine, that's it's an indicated reason to to be on it. I love this question. We get asked this all the time and I would like to hear your opinion on it. Is it true that you have to be on GLP once forever? That's a great question. So, the data that we have now is you tend to a lot of the weight that you lost tends to recur. That's a lot of times if

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tends to recur. That's a lot of times if because you go back to your old bad habits. If you go back to eating a lot of the same things that you did before you were on these medicines, yes, a lot of times you'll regain the weight. Some of the effects are long lasting. Like if you learn portion control, if you help for you can very well more or less cure your diabetes by being on these medicines. Uh and then if you maintain a lot of those same habits, then a lot of times we don't see weight gain come back. some of the newer medicines that you were alert all alluding to or we were alluding to, you don't have that weight gain. So, I tell people if you can be on these medicines, I am very confident in the next couple years, we're going to have something that's even better and greater. And uh one of these medicines is actually a long version that after you come off it, you're not seeing that weight gain come back. So, uh it's still a really exciting area. Yeah. Someone asked recommendations for pmenopause and GLP1s. Can we talk about hormones for a second and and these medications how they act on our hormones and how they help? Yeah. So the we alluded to it ear a little bit earlier with PCOS. So these medicines act directly on follicular f your ovarian follicles as well as fat cells adiposytes that help regulate hormone levels. uh they improve estrogen levels, they improve testosterone levels um across the gamut. They they're they're helpful specifically in pmenopause when you have a lot of fluctuations in hormone levels that it can occur hourly. It seems like minute to minute and you have, you know, go from hot to cold and hot flashes and you can be pretty miserable. A lot of the current therapies that we put people on are the same types of pathways that GLP-1 medicines work on. So when you're talking about uh keeping kind of the homeostasis and things in check so you're not having those wild fluctuations, we are seeing some kind of

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fluctuations, we are seeing some kind of observational data that this is helping especially hot flashes in particular uh in the in that pmenopause period. have someone that just asked any evidence of these medications working to reduce calcium artery scores. That's a great question. So, uh, yes, but calcium artery scores in and of itself can be a little bit biased because if you're already having calcium in the artery, then it's already formed over. It's already a hard plaque. It's really not going to go away. Where it really helps though is in the stuff that's not fully calcified yet because then it has time to regress. Once it's calcified, it's essentially, think of it as a stone. It's not really going to go away when it's completely formed. What we care about is the stuff that can continue to grow. And so if you can get on those early and help regress some of that plaque formation, then that's really the the higher risk stuff that we're targeting. And yes, by all means, GLP-1s can help those kinds of plaques. Susan said, "I asked this earlier, but as an electrphysiologist, do you think there may be benefits for AIB from GLP1s?" Yes. And this study is coming out next month. I'm so excited. So, atrial fibrillation and uh GLP1s are coming out and uh it's I'm so excited. I saw the results early and they're they're profound. So, yes, absolutely. And it's for a lot of reasons. We talked about it's because in the heart, but the reason for atrial fibrillation is because you have little bits of scar and in your atrium and that signal kind of goes all haphazard and goes all crazy and that's what can cause atrial fibrillation. So if we help decrease that fat and decrease that inflammation in the heart then atrial fibrillation doesn't have as much of a a pathway as much effect the in exerting itself. the normal signal kind of goes through

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normal signal kind of goes through unchanged so that atrial fibrillation doesn't happen. Just asked, do GLPS or GIPS have benefits for someone with epilepsy or should it be avoided? That's a great question. I I man I do not know that answer. That is an I've been doing this for years and that's the first time I've been asked that. I would not I'm not going to comment without knowing for sure. That's an amazingly good question. Which peptide for AIB? Someone just brought that in. So that's a great question. This this the GLP and GIP are have shown or will show to reduce AIB. The one colorary to that is the triple agonist. Rea has glucagon agonist as well. Glucagon is expressed very highly in the heart specifically in the right atrium. I wrote a paper this I love this topic and what else lives in your right atrium the sinus node which is the main pacemaker cell of the heart. So when you give glucagon agonist your heart rate goes up. So there's are a little bit of an arrhythmia risk that you see with that triple agonist that you're not seeing in the other medicines. That's really interesting because a lot of people are uh saying that that's a side effect of reta right the um Angel just came back and said my question is about COPD not sleep apnea I'm referring to the respiratory system and lungs specifically uh the benefit of GLP1s on COPD. Yeah, that's a good question. Unfortunately, COPD has been a major exclusion for uh a lot of these trials. And the reason for that, there really isn't a great explanation for why. You can hypothesize that COPD is a problem with lung expansion and your lungs are kind of chronically enlarged. And if you can decrease that abdominal pressure through

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decrease that abdominal pressure through weight loss or other mechanisms that that the lungs may have improved compliance is the word. The other thing that it may improve is the inflammation in the lung and the scarring in the lung. You're seeing this in other body systems, so it makes sense mechanistically why it may help in the lung. But unfortunately, a true study of COPD and GOP1s hasn't been done, but it seems mechanistically like it would work. Okay. Sorry, I'm there's a lot of questions coming in. That's good. Filter them. But um could someone diagnosed with Graves disease continue to use tears to potentially regulate heart palpitations and heart rate? So not for this medicine. So because these medicines in some ways increase heart rate especially with the triple agonist but you for on population levels one or two beats even with GLP1s it's not great at regulating heart rate. there's a lot better medicines at regulating heart rate. Uh I also you always worry so one of the the major risks with these medicines is PE patients that have thyroid or medelary thyroid cancer. Uh that is a absolute contraindication. Graves disease isn't a cancer by any means but there are some concerns when you have thyroid disease and taking these medicines in general. Okay. What if you have thrombophilia? Can you take GLPS or is there a certain peptide that would be safe for thrombophilia? That's a good question. So there isn't a specific contraindication for having low platelets uh to not be on GLP-1 medicine. Sometimes the reasons why you have thrombophilia may be an exclusion criteria. There are certain cancers that can cause it, but in the absence of anything that's the direct cause of your thrombophilia, then

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direct cause of your thrombophilia, then there's no real contraindication from a GLP standpoint. All right. Okay. I think we we're gonna Oh, Hashimoto's. That's another one where we have so many people who are Yeah. Can we touch on that real quick? And arthritis, any sort of immune disorder. Can can you touch on that? Yeah. So the the arthritis is a interesting one. There's lots of different reasons why you have arthritis, seratic arthritis, rheumatoid arthritis or just osteoporotic arthritis. The a lot of the autoimmune stuff is underexplored. The a lot of the observational stuff for one that just came out literally in January of this past year showed that there's market improvements in rheumatoid arthritis with GLP-1 medicines. thyroid disease. Again, similar other end of the spectrum from Graves disease, but with Hashimoto's, you'll always have people that get a little bit nervous when they see thyroid disease and GLP-1 medicines. It takes somebody that really understands you and your personal story and the your personal risk factors to kind of have discuss the risks and benefits. Um, so it's it's never something that I just unilaterally say, but it's definitely a conversation to have with your individual physician. So Dr. Sager with just a few minutes left before we wrap up. Um we have a huge population more and more people I mean several two three years ago when we came out with the compounded uh simaglletide like it was new still a lot of people didn't know about it but it's becoming very common now a lot of people are hearing about it they're trying it they're reaping the results all right so we have this population that's taking it we have a 70% overweight population right let's assume that this 70% se sees the improvements what next what will happen next where do you see the future after semiglutide I that's a great question. I think that if we can as a society control a lot of these things that are causing a lot of

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these things that are causing a lot of comorbidities in the population like uh being able to have improved mobility, the the just the general day-to - day living that a lot of people may have some difficulties with getting around symptoms. It's it's a really exciting time that a lot of these things can be curbed or definitely improved upon. Um a society where you can get out and move and have much more mobility is definitely a happier society in my mind. Keeping people out of the hospital is such a benefit. Uh you go from treating you go to helping prevent disease instead of just treating disease. And that's a much more enjoyable conversation to have just society-wise. Uh long term, I think there's a lot of unexplored stuff that we could be doing. A lot of the work that I'm doing is trying to identify who benefits most from these medicines. Uh and hopefully the next time we talk, I'll have a lot more on that topic as well. Uh but yeah, I think that there's a lot that's changing. There's so much that's coming out. I I hope we have these regularly so that we can continue to keep up to date with everything that's uh coming out in the studies. I know. And so much is changing and you mentioned that for the first time in a long time the obesity rate is going down slowly which is it is going it's like the health care cost of the nation and the overall health if we can get a healthy society imagine how much more productive we can be and those quality years. My god. Um so this is it's an exciting time and I'm looking forward to where things are going to go in the near future. Thank you so much as always. We love having you here. Please come back. Please educate. Bring the information that you're gathering to us. Thank you so much and thank you all for joining us this evening. Thank you Dr. Seager. You're wonderful. Of course. It's always a good time and thank you for all the work you've done. It's uh

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for all the work you've done. It's uh absolutely impressive and you're doing it the right way as I always say. So keep up that as well. A thank you so much. Well, that wraps our Thursday educational series, everyone. We'll see you very, very soon. Thank you again. Have a great night.