Okay, so our next speaker is Dr. Pam Tubb who comes to us from UCSD. She's gonna be speaking about an update on obesity in the cardiovascular health era, management tips from lifestyle to medications. Pam. Well, it's wonderful to be here as part of this session. And I am excited to share with you a lot of my clinical practice. I've been using GLP-1 receptor agonists and various lifestyle strategies for over a decade. And I think the synergy between pharmacology and lifestyle is really important. And that's what we need to harness for the benefit of our patients. So I'm gonna talk about both lifestyle and some aspects of these medications. These are my disclosures. And remember to have your apps so that you can participate in the questions. So I'm gonna start by reviewing evidence-based lifestyle strategies for weight management and also to improve overall cardiovascular health. When I talk to my patients about weight, I tell them not to focus on just that number, but to really focus on their overall cardiometabolic health. And I really look at a lot of other parameters such as looking at their lipids, their blood pressure. And then I'll talk about GLP-1 therapies for management of obesity. And then I do wanna talk about some side effects that we have very little data on and that's how can these agents impact muscle and bone. And then I'm gonna talk about what I do in clinical practice, which is really combine lifestyle with GLP-1 receptor agonists. So when you talk about lifestyle, it is something that really has a lot of poor evidence. And our poor patients, they're preyed on by so many advertisements and by this billion plus dollar supplement industry of all these things that can help them lose weight, improve their health. But very, very little of this is evidence-based. And so we have to curate the right lifestyle strategies for our patients. We can't let them do whatever they see on the internet. And so the way I define lifestyle is what you eat, when you eat, and how much you eat on, eat, sleep, and move on a daily basis. That's really what lifestyle encompasses. And these are the things that we should be talking to our patients about. And so this is from a review that I did for the American Journal of Preventive Cardiology, really kind of illustrating all the things that we should be talking to our patients about. So first, quality of their diet. And this is where, again, there's so many different fad diets. There's the South Beach diet, there's Atkins. There's just too many diets that are marketed to our patients. And so we need to focus on the basics. And what are the basics? Well, a lot of what we know is based on evidence from studies done with the Mediterranean diet, which really focuses on decreasing processed foods, sugars, and really focusing on increasing our consumption of vegetables and also lean meat. So I really focus on a very evidence-based diet and really steer them away from what I call these gimmick diets. And then there's also the quantity of what we eat. And just because you're eating very healthy, it doesn't mean you can eat as much as you want. So I really also personalize the recommendation for their caloric intake based on a lot of factors, age, their weight, and other comorbidities. And so that's also important to think about quantity. And then I've done a lot of work on time-restricted eating, so I'm probably biased. But one of the things that I always focus on with my patients is we shouldn't be eating for 16 to 18 hours a day. That's just not how humans were meant to eat. We really should be limiting our caloric intake to a specified period of time. That's how our ancestors, the hunter-gatherers, the cavemen, they ate. They ate when the sun came out, and they stopped eating at night. But in modern society, we eat all the time. So a typical patient of mine will stop eating dinner at nine. After dinner, they'll have another snack. Then because they have poor sleep or sleep apnea, they wake up in the middle of the night and have a midnight snack. So they're exposing their cells to constant stimuli for about 16 hours a day, and that's just not how our biological systems are meant to operate. So the simple thing I tell patients is really avoid snacks after dinner. That's how I start. And then we work further on refining that, but that's the first thing you can start with with your patients is avoid those after dinner or late night snacks, because they typically tend to be unhealthy. And this is a graphic that I created about just synthesizing all the things that you want to talk to your patients about, the content of their food, the amount of calories that they are consuming, the duration by which they're consuming their calories, meal frequency, and this needs to be personalized. And I've started to use continuous glucose monitoring in my practice to figure out what's better for some patients. Some patients, it's small meals throughout the day, and for some patients, it's larger meals. And so that's still an area of evolving research. So lifestyle modifications are great, and I start with that, but what we know based on so much mechanistic understanding is that's not enough. I mean, I have patients that do their best. They really try to do everything, and they can't lose weight. And what we've learned is a lot of our patients need some additional pharmacologic help, and there is nothing wrong with that. And so when we look at the spectrum of weight loss, we see that with lifestyle modifications, we're gonna get two to 5% weight loss. And we all know that adherence is very difficult, and so sometimes it's not sustained, and people are yo-yoing. They lose weight, they regain it, which we also know is not very healthy. What we have now is a new era where we're able to offer patients GLP-1 receptor agonists that can help synergize with lifestyle in producing more weight loss. We also have other more invasive procedures, both from an endoscopic perspective and a surgical perspective that can produce even more weight loss. And I'll tell you, in this era, I rarely refer patients to bariatric surgery. I can usually make a great dent with a combination of pharmacotherapy and lifestyle. And so Mike already talked a little bit about the GLP-1 receptor class. I love to put the picture of the Gila monster from Gila, Arizona. It's in the spit of the Gila monster that the GLP-1 receptor agonist molecule was identified, and the first GLP-1 receptor agonist on the U.S. market was Exenatide that was introduced in about 2015. But what we have is a really pleiotropic compound that has a wide variety of physiologic benefits, not just weight loss. Decreased inflammation, decrease in liver fat, improvement in kidney function. So really a very beneficial compound, almost analogous to our statins that have so much pleiotropic benefit. There is a difference in the magnitude of weight loss. And so what we know is, as you heard from Mike, that tercepatide produces more potent weight loss. But the question is, is weight loss alone enough to improve overall cardiovascular health? So now let's turn to an ARS questions. Are you concerned about the impact of GLP-1 receptor agonists on skeletal muscle? Yes, no, or unsure. ♪♪ ♪♪ Okay, I think, and we should be concerned. Just with any category of drugs, we always have to be cognizant about side effects. And one of the analogies that I make is there used to be a drug called Fen-Phen, and I still take care of patients in my practice that have valvular disease from that, which was a weight loss drug. So we always have to be cautious, and we always have to be looking, not at only the short-term gain, but what's the long-term sequela of these medications? And we really have a big data gap here, because there's really a lot of conflicting data on whether there is any clinical reduction that's significant in skeletal muscle. And a lot of the studies that we have, it's based on DEXA, which is looking at body composition, and it gives you a measurement of skeletal muscle mass. But it doesn't give you skeletal muscle function, or it doesn't give you skeletal muscle architecture. And we're gonna talk about that shortly. So DEXA is a very imprecise way of looking at what's happening to our skeletal muscle. So the question is still unanswered, and we need a lot more data on it. And there's also a question about what happens to bone, because bone and muscle are so intricately linked. It's a very tight scaffolding between the bone and the muscle. And so when the muscle gets weak, is there a problem with the bone? And when you look at the label for semaglutide, you see that there is a little bit of a difference, but again, in terms of fractures, but it's very, very, very minimal data, and you can't draw any conclusions, but we need to be thinking about it and designing future studies. The other thing we need to be really careful about is this concept of sarcopenic obesity. As we age, we do lose skeletal muscle mass. That's just a natural process of aging. And so we really have to counter what happens with natural aging and potentially what happens when we give our patients these drugs long-term. And one of the simplest things you can do is really encourage your patients to do strength training. So I don't write a prescription unless my patients agree to do strength training and also agree that this is a lifelong medication. This is not a medication they go on and off of, because that's one of the worst things that you can do is do this yo-yo rebounding of weight loss and weight regain, which we do know is not healthy in many aspects. And so we do need to think about just sarcopenia. And as Mike had mentioned in his closing slide about some of the newer agents in development, there are clinical trials ongoing with agents that can actually enhance skeletal muscle mass. So if there's something that I could leave you with, I wanna talk to you about how to think about this. Okay, so you have on one side, you have this nice, juicy Wagyu beef. And what it has is it has a lot of fat that is interspersed in the muscle. And then on the other side, you have a piece of very lean meat. Well, if you did a DEXA scan on these two animals, the muscle mass in the Wagyu beef would be much higher. So your DEXA readout would be, oh, there's higher muscle mass. But this isn't telling you the story because what we know is when you have a lot of fat in your muscle, there's a lot of inflammation. And the function of the skeletal muscle is not as robust. And so what we really need is better imaging studies to look at the architecture of the muscle. And we also need functional studies because my theory is that what's probably happening when we give our patients these medications is probably what I call the delipidation of the skeletal muscle, where you're actually removing fat, which then when you measure on DEXA is telling you that there is decreased mass. But it's truly not what you think about in terms of there's actually decreased mass. But that's my theory. We have to do the studies. And again, this is an area where there's a big data gap. And I encourage you to tell your patients to do strength training. And there's very simple strength training videos that you can give them links to that they can just do at home, 10, 15 minutes, a couple times a week. And it will just also help them in general with age-related sarcopenia. And so we do wanna be thinking about the way we use these medications clinically along with lifestyle. And here's an example of how lifestyle is very synergistic with the use of these medications. So giving them a very specific exercise regimen to do. And also the other thing that I'm seeing is a lot of people, because they lose a lot of weight, they think it gives them a license to eat whatever they want. I remember hearing from some of my colleagues in the early era of statins, that's what a lot of people were doing. Oh, my LDL is great. Let me eat whatever I want. And so we still need to talk about all the lifestyle therapies. And when you use lifestyle and pharmacology together, it's not one plus one equals two. It's one plus one equals 10. It's a great synergy. And again, as a cardiologist, I don't talk to my patients about the weight per se. I talk to them about how do we improve your overall cardiometabolic health and improve cardiovascular outcomes. Because weight is also a parameter that if you don't look at it in the right way, sometimes you can be fooled. There can be somebody who weighs a little bit more because they have more skeletal muscle mass. And there's people that I call skinny fat that are extremely thin. But when you look at body composition, they have a huge amount of visceral adiposity. So we can't hang every clinical decision on just weight alone. We have to look at the broad cardiometabolic aspects of the patients. So another ARS question. A 55-year-old woman with a history of hypertension, ischemic stroke, and obesity presents for follow-up. She was started on semaglutide 0.25 sub-Q week six weeks ago. And she is having significant nausea since starting this. So what do you recommend? Do you switch her to triseptide? Do you stop the GLP-1 receptor agonist? Do you just tell her to stop eating when she starts feeling full? Or do you prescribe an anti-emetic that can be concomitantly administered with her GLP-1 receptor agonist? ♪♪♪ ♪♪♪ Okay, most of you got this right. That's exactly what you would do. A lot of the side effects of these agents can be mitigated with just simple strategies, such as telling them to eat smaller meals, to eat slower, because that's one thing that I noticed we all do, is we eat really, really fast because we have so many things to do. But just eating slower allows the mechanisms that make you full start to give you that feedback that you need to stop eating. And then other things that I see commonly is constipation is a side effect, but it's because people are drinking less water. When they're eating less food, they're drinking less water. So also telling people to just hydrate better are just very simple things you can tell patients to reduce the side effects and increase adherence. So really, it's about combining everything. It's about making the right changes in terms of their diet. It's about also having them exercise and then adding on pharmacotherapy and really doing those in a way that is synergistic and really yields even better outcomes than what we see with one therapy alone. And so we're really in an incredible era. And thanks to people like Mike and Leslie for leading some of these landmark clinical trials that have given us some powerful data on the cardiovascular benefits of these GLP-1 receptor agonists. But we also need to be thinking about lifestyle modification, especially in thinking about potential long-term effects like sarcopenia. And we really have at our fingertips some incredible data, not just with the GLP-1 receptor agonist, but in the whole cardiometabolic space. And we need to really harness all of those benefits to improve clinical outcomes. Thank you.

lifestyle changes

GLP-1 receptor agonists

obesity management

cardiovascular health

personalized dietary plans