All right, everyone, welcoming you to our webinar this evening. Excited to participate with all of our faculty this evening. I'd like to introduce your lead speaker this evening, Dr. Almendos, as we address the second part of the series in reframing obesity, addressing stigma, myths, misconceptions, and patient concerns. Wonderful. Thanks so much, Dr. Chadha. So welcome, everyone, to the next part of our series on reframing obesity. This week, we're going to cover separating fact from fiction, debunking common myths. I'm honored this evening to be joined by my colleagues, Dr. Mona Chadha, Dr. Maria Mogollan, and Dr. Jennifer Clemens. I'll let them introduce themselves. Hi. Good evening. My name is Mona Chadha, Dr. Chadha. I'm the head of endocrinology at Chavez Medical Center, which is part of the Ochsner Health Care System. Hello. Good evening, everybody, and welcome to this series. My name is Maria Mogollan. I'm a foreign physician, internal medicine, specialized in obesity and diabetes, and also an APRN here in the United States, and also a clinical faculty at MRU. Hi, everyone. My name is Jennifer Clemens. I'm clinical professor and director of pharmacy education with the University of South Carolina College of Pharmacy, and so I'm happy to join the panel for this second part of the series. Wonderful. Thanks, everyone. So I'm Jamie Almendoz. I'm a medical director of the Weight Wellness Obesity Medicine Program at UT Southwestern in Dallas, where I'm also an associate professor of medicine in the division of endocrinology. So let's get started this evening. Here are my disclosures as the main presenter. The objectives for today's session are going to be to tackle common misconceptions about obesity medications, including their effectiveness, potential for dependence, and intended use. It will provide accurate information to help healthcare providers make informed decisions. And so we're going to start with a case, and we'll have a case at the beginning of each of the three sections tonight. And this one involves a 42-year-old woman who has a BMI of 36, so class II obesity. She also has a history of prediabetes and moderate obstructive sleep apnea, who's presenting for weight management. She expresses frustration after being told by a friend that weight loss medications are only for people with morbid obesity, and she should just try harder with diet and exercise. What's the most appropriate response to address this misconception? Is it A, obesity medications should only be considered for patients with a BMI of greater than 40, as they are not effective in those with lower BMIs? B, obesity medications can be appropriate for patients with a BMI of greater than 27 with weight-related comorbidities, as they can help to improve both weight and metabolic health? C, lifestyle changes alone are always sufficient for weight loss, and medication should only be used when all other options have failed? Or D, weight loss medications are only for short-term use and should not be considered for someone with a BMI of 36? And so we'll have you put in your answers, if you can, to the question. Is this something that you guys see in clinical practice, where people come in thinking that they may not qualify for obesity medications? I see a lot of that in our practice on both ends of the spectrum, where some people think that obesity has to be considered severe, whatever that means to the patient in particular, to qualify for the medications, and then others on the other end of the spectrum who may actually have a normal BMI, but who are dealing with insulin resistance or prediabetes, polycystic disease, et cetera, wonder if these medicines might be considered for them as well. And so I think we definitely see a mixture of experiences and perceptions with our patients. Absolutely. There's so many things that are challenging here, and we're going to kind of go through the polling questions at the end of the section. So we have a woman who has class II obesity that's complicated by prediabetes and obstructive sleep apnea. And what we're doing is working out, well, what are the next best steps for treating obesity in this individual? I think the challenge is when you look at obesity, it's highly prevalent in society. Current rates are 43% of US adults are living with obesity, and projections say that by 2050, we're looking at north of 60%. And with that comes a host of complications, including rising rates of diabetes that they estimate will go from about 16% currently to over one in four individuals in the US. And so what we have is an epidemic of not just excess adiposity, but also cardiometabolic complications. And we need to know how we're going to tackle this rather than just leaning into kind of things that we think we know about. When we look at the prevalence of lifestyle factors that can be contributing to obesity, such as low diet quality, inadequate physical activity, inadequate sleep, I mean, that sounds like a healthcare provider's life right now, right? I know this is my life these days. The prevalence of these things, it's really high, right? And so we have a lot of our patients who come in going, I know there's room for improvement, but we're human. And so many of us, we're just trying to get by. And so the question is, is this the answer? Can we really kind of put the toothpaste back in the tube by saying, well, I may have created this positive energy balance in my life and accrual of adipose tissue in places that it's meant to be in ectopic places where it's not meant to be because of inadequate activity and excess intake for a variety of different factors. Can we undo this with dietary restriction, physical activity? What research would say, and this is kind of a condensed version of many, many studies of varying quality with, it comes to, well, what kind of diet is best for us? Is it low fat, low carb? Well, it turns out they're kind of equally effective, but also have limited durability of effectiveness. When we look at physical activity, we'll lose more weight if we increase the intensity of activity, but there's also limited effectiveness in terms of durability of the weight reduction. And I think this is really challenging when patients are told by friends, loved ones, or even their well-intentioned clinicians, that this is all they need in order to achieve a healthier weight. That can be really problematic and not helpful. Do you guys have a lot of patients who come in to see you who feel that if only they could work out harder, they'd be able to lose the weight that they need to in order to be healthy? Totally. Totally. And I even see the opposite. Some people are doing a lot of exercise and they're doing weight training and they're gaining weight because they're gaining muscle. So they get frustrated because they're doing basically everything that should be improving their health and they're gaining weight and it's about body composition also. So definitely this is something that we need to keep in mind that it's not the number on the scale. It's about a comprehensive evaluation and treatment for this. What about you, Jennifer? Is this something that you tend to kind of hear from kind of patients and clinicians in this realm? Yeah, definitely. I think one thing that I always try to remind the patient and even the team about is that we just need to educate. I think having access to the internet and a lot of different resources, people go out there and they read on their own what they should be doing. And we know that sometimes social media may drive their type of dietary pattern for that week or that month, that year, their physical activity changes. But I think if we use the evidence to help them make better choices, better modifications in their lifestyle habits, that's where we really can have a part in their weight loss journey for success. Absolutely. I reinforce the patients, these are health behaviors, but we shouldn't conflate a healthy behavior with a weight loss behavior. And these will always be foundational for avoiding cardiovascular disease, preventing dementia, avoiding cancer. But these may not ultimately help us to get to the weight we want, which can be why it's important for us to consider beyond this, the use of medical therapies that are evidence-based. So this is a very kind of complex slide. I encourage our viewers tonight not to be overwhelmed by this, know that it will be in the enduring materials that you'll be able to see online. But this is kind of a condensation of available FDA-approved anti-OBC medications that can really help us to achieve clinically meaningful weight loss. They are indicated for people who are living with a BMI over 30, or those with a BMI of 27 with a weight-related complication. We have everything from kind of specific GI acting agents, such as Orlistat, that decrease absorption of dietary fat, to stimulant-based medications, such as phentermine, with and without to Pyramid, that can help to alter or suppress appetite by acting in different places in the brain. Bupropionaltrexone in combination can also be useful to act in the reward system within the brain and be helpful for craving and other actions. And then also kind of the newer generation of anti-obesity medications that everyone seems to be talking about these days, the GLP-1 receptor agonists, such as loragatide and semaglutide and trizepatide, that don't just work in the brain, such as most of the other medications, but also have impacts on the gastric emptying and motility in a way that helps us to feel full with less for longer. And I think when we talk with many of our patients who've experienced these therapies, there's something different about treatment with this that they kind of, if you look at social media or the news, people call it game changing, because what it does is it takes a lot of the accounting function of restrictive dieting and turns it into a different kind of, let's say, process whereby we can focus in on what our body needs rather than what we're not supposed to be doing. And I think for many people who've tried to lose weight through restrictive dieting, often for decades, this can be a different kind of tool that works differently. But we're going to talk about the other effects too, beyond that. When we look in the landscape of obesity care and treatment and compare what we have in the green bar here, lifestyle modification alone, where we have this non-sustained kind of three to 7% weight reduction, and compare it with what many would say is, well, one of the most effective tools for weight reduction, bariatric surgery, what we see is that older generations of anti-obesity medications, such as the fentamine, naltrexone, bupropion, etc., and loraglutide, as a first generation GLP-1, what we see is that really you're getting 5% to 10% weight reduction with these agents. And when we look at this newer next generation, where what we're seeing is on average 15% to 20% weight reduction, we're seeing that we're really kind of starting to bridge this gap now between lifestyle interventions and bariatric surgery without having to have surgery. And so that's great that we're able to achieve this magnitude of weight change. Do you guys have a lot of people coming in talking about, hey, I think I want bariatric surgery these days? Not so much. Not nearly as much as previously. And I find it interesting. I know that when I counsel patients about the use of the GLP-1 RA agents and the GLP-GIP agents, I give them the same advice as they would get from the bariatric surgeon, to stay hydrated, focus on protein. And I know that we're going to be talking about these more, but this is a medical way of achieving that same sort of weight loss. Absolutely. Jennifer? Yeah, I think that this will continue. I mean, this is what we have currently available. And if we think about the landscape of these drugs, they've kind of continued to push towards bariatric surgery. And so I think too, we also think about what's in the pipeline and what could potentially come out and how it could push closer and closer, maybe to 25% or between 25 and 30%. So I think the trend that we're all kind of agreeing on that people don't ask about bariatric surgery will continue to, you know, we'll see that in practice with new medications. Absolutely. And, you know, I still think there's definitely a role for bariatric surgery for people with very high BMI. But I think we need to look at this in terms of ands, not ors, in terms of what is best for our patient. What does the evidence say? And what is really the goal of treating obesity? You know, it's really not the number on the scale. And we almost seem to have an arms race now with regards to which agent can help people to decrease the most weight. But I think what's important in the context is there's a lot of variability. And not everybody responds in the same way to a diet, to bariatric surgery, nor to these new medications. And I just like to highlight for people that there's a lot of variability. And so when we look at studies around weight reduction, we often hear what the average or the mean weight loss is. And our patients are far from average. We're far from average, right? And what we want to acknowledge is there's a lot of diversity in the people who we treat, and also diversity in terms of the response. When we look at the vertical, excuse me, dashed red line, everyone to the left of that actually gained weight in the study. And so we need to acknowledge that there will be people who do not respond to these medicines in terms of weight reduction. But also there's a diversity in terms of response from a weight perspective and a cardiometabolic outcome perspective too, because really with these new agents, we're not just decreasing body weight, we're treating in a broad sense. And it's important for us to acknowledge that so we can have more informed discussions with our patients and be able to read the results of studies more effectively. When we look at kind of the outcomes and particularly kind of think about this patient, you know, what we're looking at for somebody with prediabetes, the fact that we have data that these medicines are effective for reducing weight, that there's durability in terms of the effect. These are three-year data from the terzepatide study, Surmount-1. And then what we see is for people with prediabetes who were followed in the study, and this curve, these curves here are for people with prediabetes who were treated for three years with terzepatide. What we found is that, what they found in the study is that more than 90% of people with a history of prediabetes then had healthy, normal range blood glucoses at the end of it. So these are effective therapies that don't just focus in on sustained weight reduction, but also the cardiometabolic benefits that we see with having lower levels of excess adiposity and visceral adipose tissue also. But there's more to it. So if we recall our lady in the case, she had a history of prediabetes and she also had a history of moderate obstructive sleep apnea. We know that these medications can also be impactful for treating obstructive sleep apnea. These are data from the Surmount OSA study that looked at people living with obesity and moderate to severe obstructive sleep apnea after treatment of one year with terzepatide. And what we see on the left hand side is average weight reduction in this part of the trial of about 18% body weight reduction and significant reduction in the AHI or apnea hypopnea index of about 27 plus events per hour. That's a major reduction in terms of events per hour. The overall mean apnea hypopnea index for the population was about 51.5 events per hour. So pretty high AHI levels in these patients. And what we know from clinical practice, many of us, is we have many patients living with obstructive sleep apnea who we see for treatment of obesity, who when we talk about, you know, would you consider getting tested? I see that you're on two, three blood pressure medications. Didn't you say that your spouse says that you snore and that you're not breathing great when you're asleep? When you bring up sleep apnea testing, what's a typical response from your patients? What do you all hear in clinic? I know in my experience that patients may say, oh, yes, I've been tested, but I don't use the machine. Or you know, there's they there tends to be a dismissive sort of opinion of how sleep impacts overall health. And we know that there are a number of hormonal sequelae that are impacted by interrupted sleep. If we could look at some of the comments and questions being brought up in the chat, as we've been going along, people are saying that, yes, patients are requesting surgery less and medications more. But some people actually need both, that we don't necessarily have to look at this as an either or situation. But some patients need both in order to have a sustained response. There are questions about, will insurance cover for sleep apnea? I don't know if you want to address that, Dr. Almendoz. So which questions in particular about sleep apnea? Insurance covering treatment for sleep apnea, a couple of people are asking about insurance coverage because it's being advertised on television. And one person commented that they've actually tried to use the Surmount OSA trial to justify, I guess, in a prior authorization process, but still get denied. There appears to be a lot of lag with regards to indications beyond obesity treatment for coverage. What we're seeing in our patient population is, for these added indications, such as cardiovascular risk reduction or obstructive sleep apnea right now, these are being covered with those who are Medicare beneficiaries, but not those with commercial plans. And I think that's pretty much the same across the country, no matter what you say or do right now. There seems to be a hold right now in people paying for additional indications by itself. If they have obesity care covered, then it's covered, but not for the separate indications. I think hopefully there'll be more advocacy and traction in this space, but currently not for now with that. And so I think those are great questions, because it's very exciting to have treatment options. And as you said, Dr. Chadha, many patients will say, well, hey, I've got the CPAP, but I'm not using it. Those are the people who, one, actually got tested, got the CPAP, and actually considered using it. So many patients, I think, my colleagues in primary care and others, say, well, you know what? I suggest to patients that maybe they could get tested, and they'll say straight out of the gate, well, I'm not going to wear a CPAP, so I'm not even going to go and get tested. And I think now that there are potential options for treating, I think this is great. I think what we need to be aware of is that it takes time for these reductions in HI to happen, and likely much of this coincides with weight reduction. We don't know what the magic cut point or sweet spot is for, at this point, you don't need CPAP anymore. And so this may be a case of and, particularly if somebody has symptomatic obstructive sleep apnea, daytime somnolence, especially if they're working in something such as a commercial driving or something, you really want to make sure you're treating their obstructive sleep apnea, not just hoping that things will get better quickly because of pharmacotherapy. So we need to look at this as kind of holistic care and treatment. I think it's important to highlight that, you know, about 40% or more people in the trial who were treated then kind of experienced kind of, we can call it a clinical remission where they no longer meet criteria for CPAP based on their response. And so, you know, it's exciting to have options and let's continue talking about that. So to get back to our question, you know, we're going to kind of pull again quickly. I think many of you kind of got the answer looking at kind of what the response was in terms of the most appropriate response to address this misconception here that anti-obesity medications can be appropriate for patients with a BMI greater than 27 with weight-related comorbidities as they help to improve both weight and metabolic health. So again, outdated terms like morbid obesity or stigmatizing based on our other kind of content within this series, you'll know kind of about weight stigma and bias and language that we can avoid using as part of obesity care. It's important for us to be mindful that there are specific indications for obesity care and treatment and that patients can access obesity medications with BMI 30 or greater or 27 or greater with a complication of comorbidity related to their weight. And so this is kind of the rationale here that we just pretty much went through. And in the interest of time, we're going to go on to the second case. So we have a 55-year-old man with class 2 obesity, BMI 36. He has a history of coronary artery disease and metabolic dysfunction associated stiato-hepatitis, MASH, formerly NASH, and he's hesitant to start an obesity medication because he's heard that these drugs are addictive and that stopping them will make him gain his weight back. Do you guys see people who don't want to start a medication because they don't want to be on it forever? I see some nods there. You know, we encounter this all the time, especially things like statin therapy, right? Well, why would I take this if I have to be on it forever? What kind of conversations do you have in order to kind of circumvent that? I think this is a conversation that we kind of like have with all our patients about using this type of medication. And when we focus on weight, of course, that's not going to be the right way. We try to always focus on the health, overall health, that this type of medications will provide to the patient, always related to health and not related to the weight. Yeah. And so, you know, not that this is a politician's answer to my patients, but the way I approach it is, you know, I've heard that your goal is that you want to be able to get your BMI below 35 so that your orthopedic surgeon will let you get that knee replacement done. Why don't we focus in on that goal, get you where you want to be, where you feel healthy and comfortable, and then at that point, we'll work out what we need to do in order to keep you there. That way, what we're doing is we're reinforcing to the patient, this is your goal. I'm here to help facilitate that and get you there. Let's be goal oriented. And then once we're there, then we'll talk about what we need to do. I don't think that's smoke and mirrors. I think that is a way in which we can help to acknowledge patients that were there to work with them on getting to their goals. So what we have is, you know, a question here, which of the following is the best explanation to address this concern? And of course, there are many ways to go about this. Is it that obesity medications work by altering brain chemistry in a way that leads to physical dependence similar to opioids or benzos? Is it while weight gain can occur if the medication stopped, this reflects the current nature of obesity rather than dependence and continued treatment may be needed for long term weight management? Is it C, it's true that all patients regain more weight than they initially lose after stopping obesity medications, so they should only be used for short term weight loss? Or is it D, obesity medication should not be used in patients concerned about dependence, and he should rely on lifestyle interventions alone? All right. So I'll wait for the audience to kind of answer before we move on. But you know, I think this kind of brings up many kinds of concerns that patients have about requiring to take a medication long term. Are these short term, I hate to call them fixes, many patients will come and say, you know what, I just need to kickstart to get my weight down a little bit, then I'll be able to move a little bit better. And then I'll be able to get more weight off and keep it off. And while I wish that were true, many of us who work in the clinical space know that especially as we get older, this is more and more of a challenge, because the way in which our metabolic processes work, we're not going to be able to buffer calorie intake and other things in the same way through physical activity in a way that's meaningful. But we need to consider what does it mean beyond weight reduction. When we look at the impact of treatments such as this, and our gentleman in the case has a history of coronary artery disease, he's post event, had two stents in his LAD about three years ago. When we look at the role of treating obesity in high risk cardiovascular complex populations, the select trial really gave us some great data that showed for people who had excellent standard of care, so good blood pressure control, the vast, vast majority were on great lipid lowering therapy, when you add in somaglutide 2.4 milligrams weekly compared to placebo, they saw an additional 20% reduction in three point MACE. And that's that major adverse cardiovascular event composite of cardiovascular death, nonfatal MI and nonfatal stroke. And that's on top of standard of care that was really good. And so what we see is this kind of addressing of what some may refer to as kind of residual risk with treating this. And what we see interestingly is the curve separates really early here from a survival perspective, from event perspective. And if we recall previously what it looks like with regards to weight reduction and how long it takes to lose weight, and this is in months here, what we're seeing is kind of changes before people lose a lot of weight, we need to remember that the select trial was a cardiovascular outcomes trial, not an obesity trial per se. And so you might say, well, in the step one trial, people lost on average 15%. How come they only lost 9.4% here. So different population. Remember, this was not an obesity trial with younger populations. This was a cardiovascular outcomes trial for people with a history of cardiovascular disease. They lost almost 10% weight reduction, 8% weight circumference reduction in terms of centimeters. They had great blood pressure and self control. So we see kind of minimal reductions here in systolic blood pressure and things. What I want to highlight is kind of changes in things like highly sensitive CRP. So we see like a 40% reduction in this inflammatory marker. Now we don't need to get into a debate that CRP is not a biologically active protein, all those other things like that. But what we're seeing here are improvements in things that we pay attention to in the cardiovascular space with regards to risk. And we see very nice reductions in these here as part of an obesity treatment. And is it that obesity is a pro-inflammatory disease and what we're doing is impacting this? Is it that there's something else going on? What do you guys think? Or how do you answer your patients' questions if they say, well, hey, is this just about losing weight? Because I could go on a diet and just lose weight. Or is there something special about the medicine? How do you approach this with your patients in clinic? Well, I think Dr. Mogollon touched on it before, you know, that we're looking at health, right? Not just overall weight. And certainly rapid weight loss that might not be sustainable is not in the best interest of our patients. Perhaps we could take a moment here and address some of the questions that we're seeing in the Q&A. They're actually sort of related. The first question is, does prediabetes qualify as one of the obesity complications for anti-obesity medications? And the second question is, do you recommend doing blood tests to measure insulin resistance or do you diagnose it or is it just by physical exam? I mean, certainly in the select trial, it showed significant reduction in cardiovascular risk factors overall. So, you know, in our practice, you know, how do we address and how do we define obesity and insulin resistance? Yeah, I think, you know, we'll save some of the general questions like that towards the end and we'll kind of focus in on that. I just want to make sure we get through the slide content and then we can answer some of those general ones. You know, the important thing about select is that prior to this, we knew from studies like LEADER and SUSTAIN-6 and others that GLP-1 therapies in people living with diabetes were effective for decreasing cardiovascular risk. And this was the first time that we saw an anti-obesity medication, a GLP-1 therapy, decreasing risk in people who did not have diabetes. And so from that perspective, I think it's really kind of good. Just to kind of answer the question you asked, Dr. Chadha, you know, hyperglycemia does count as an obesity-related complication that does allow that. But if you don't have obesity medicine coverage, it's not going to push people over the post. It's, diabetes is one indication for one line of brands and obesity is another indication. And there's some lore sometimes, and you'll see it in all these kind of online chat rooms, Facebook groups for obesity physicians, et cetera, saying, well, if you put prediabetes, it's going to be covered. Spoiler alert, it will not. Prediabetes is not an indication for these medications. And so we need to stop hoping. I think sometimes people will put it through. Turns out obesity medicines were covered anyway, and it creates a false narrative that if I put this down because it happened before it got covered, that's an attribution bias. It's not true. And so we need to make sure that people understand that insulin resistance, prediabetes in itself is not an approved indication for these, but it is a complication of excess adiposity. So if you do have someone with a BMI of 27 and hyperglycemia, that does count. And so there's a way to look at it, but also a way to not get frustrated in the process too. And so what we have is demonstrations here from the select trial with regards to cardiovascular risk reduction. And what we know is that these medications work in a variety of different ways that can potentially decrease cardiometabolic risk. We've talked about on the far left with regards to how they can decrease appetite, that can help with calorie reductions, and then using the adipose tissue stores that are there. When it comes to other factors, including kind of reductions in hepatic steatosis, kidney health, we know that, for example, from the flow trial in people with diabetes. So don't get confused when you see some trials. You need to ask yourself first, is this for people with diabetes or people without diabetes so that we use the data correctly in our patient population? We see improvements in kidney health. We also see kind of changes in inflammation and other things that all really amount to cardioprotection. And so when you look at analyses like this, and now this has not been kind of published, but was presented at a meeting in Europe last year, when you stratify people out who were on somaglutide 2.4 based on the amount of weight they lost at 20 weeks, what you see is almost kind of superimposable lines here. So regardless of the magnitude of weight change seen at 20 weeks in the trial, there was no difference in terms of the cardiovascular outcomes, the MACE outcomes there. And so this may not be the best way to analyze the data. It may not be the most meaningful way. There's lots of other ways, maximum amount of weight people lost, for example. But what this would suggest, at least, is to have a conversation. Are there weight loss independent effects of these treatments that are beneficial for our patients who are high risk? One of the concerns our gentleman in the case had was with regards to weight recurrence. And we know from, many of us will know from real life clinical experience from a variety of different realms, including our patient's loss of coverage and tolerance to medications, a variety of different things. That when patients discontinue medications, and on the left, we have somaglutide from the step one extension, on the right, we have surmount four terzapatide data. What we see over the following year is recurrence in about two thirds of the lost weight. Now, of course, as we showed before, there's a lot of heterogeneity or variability in terms of how much weight people lose, but also how much weight recurs, right? And what we also see is that, you know, depending on the data you look at, about 15, 1.5% of people will maintain their weight without the medications, one cessation. But that means that 85% of people are experiencing some magnitude of weight recurrence. Now, there have been papers, well, more presentations and papers with regards to potential strategies for maintaining weight loss after this, could it be low carb diet, could it be behavioral health programs, slow tapers, changing to non GLP-1 medications, but these are all involved, or the majority of them involve very small numbers of people and or are retrospective in nature. And so what we need to do is make sure that we are supporting good evidence based care, which suggests that obesity is a chronic and complex disease and that chronic therapy is effective. And this is really what we're seeing on the right hand side in the Surmount 4 data that chronic therapy is effective and discontinuation of therapy leads to disease recurrence, which wouldn't be surprising if we were looking at, let's say an LDL curve, and this was a statin trial, right? Yet, when we pull this up relative to obesity, well, this is just proof these medicines don't work. I would say the exact opposite. This is proof that these medicines are effective when we take them. But the question is, why are we stopping effective treatments, right? And, you know, we work in the real world, and there are costs and other considerations that go into it. There's tolerability and a variety of other things. And so we need to have meaningful conversations with our patients and advocate as best we can for evidence based care where we can, because there's so many things that facilitate weight recurrence and weight regain. This is not about willpower, right? And I think it's important for us to acknowledge that when people are in a weight reduced state, when they lose weight, there's an increase in hunger and food reward or reduction satiety. And this promotes increases in energy intake or calorie intake. In addition, strange changes in things like muscle efficiency means that we burn fewer calories for the same workload, which means that we're less able to compensate with physical activity in terms of calorie intake. And as those of us working in the endocrine space, we know that there are a variety of different neurohormonal changes that happen as well, including changes in sympathetic tone, changes in leptin and ghrelin, and also our thyroid hormones and function that will really, let's say, slow down our metabolism to use the lay person's term, things we hear about in clinic all day, right? I'm worried that I lost too much weight or weight cycle through my whole life and I've broken my metabolism. Our metabolism has changed due to a variety of different reasons that will facilitate weight recurrence and challenges with weight regain. So we need to validate that for our patients and not just say, no, you're wrong. You just need to eat less and move more because we know that that's not true. And what we need to do is offer evidence-based therapies, which could include a variety of interventions, not just pharmacotherapy. We do know that, you know, weight loss can be sustained with these treatments too. And specifically, we were talking about cardiovascular risk reduction, and these are four-year outcomes data from a weight perspective. And what we see is that with continued treatment with somatic 2.4 milligrams, we see sustained weight loss in people with a history of cardiovascular disease. So these medications appear to be safe and effective long-term and have benefits, not just for weight reduction, but cardiometabolic health improvements too. And I think as we look at kind of the future of this, we spend so much time talking about GLP-1s, it's almost become the moniker of these incredent-based or nutrient-stimulated hormones or whatever you'd like to call them. There's so much debate in the space about what's the best way to group these together, given that some of the new and emerging agents are not incredent or nutrient-based, but GIP, and we talked about GLP-1 and GIP combination medications, such as terzapatide being the currently approved one. But when we look, there's so many others in the space, we're looking at kind of triple agonists that include all of these three. That would be retatrutide up and coming, for example, but there's also GLP-1 glucagon combinations, such as sabotetide and others that are also in phase three clinical trials. There are amylin agonists, and there are up and coming data with regards to combinations, for example, of semaglutide with amylin, so cagresema is something that's being studied right now. In addition, there are other hormones, such as PRY. So there are a variety of different ways in which these can work, but also specific organs in which they can have effects, such as liver. So glucagon action in the liver may be a more beneficial treatment for MASLs and MASH. And so it will then kind of shift from, let's prescribe the medicine that brings about the greatest magnitude weight change to what complications or metabolic challenges is my patient facing and which is the most appropriate agent for them. So the next chapter of obesity care is not simply going to be about weight reduction. It's going to be choosing targeted therapies based on our patient's health. And when we look at further emerging data, these are data that were presented in November last year for people with a history of MASH and F2 to F3 fibrosis. This is the essence phase three clinical trial looking at semaglutide for treating MASH. What they saw in this trial was those treated with semaglutide, 63% of people experienced a resolution in their stat of hepatitis with no worsening fibrosis and a 37% improvement in liver fibrosis with no worsening of their MASH. Weight reduction, a little over 10% on average with this. And so what we're seeing is that beyond weight loss, we're seeing improvements in cardiometabolic health for things that are meaningful for many of our patients, right? Did you know that about 75% of patients living with obesity have MASLs and about a third of those roughly will have MASH. And so it's important that we now have treatments and identify opportunities for improving health beyond just talking about weight reduction, because that's going to improve long-term patient health and probably going to improve patient engagement too when it's not just about the number on the scale. I think it's important to highlight that there are a variety of different emerging kind of compounds for treating. And so this is the phase two clinical data for subodatide. That's the combination GLP1, glucagon receptor agonist. And these are for people with F1 to F3 fibrosis. And we see kind of 62% resolution in MASH without worsening in fibrosis. And so there are a variety of different agents that could potentially work differently given that this has an impact on glucagon that research would suggest may have a beneficial action in the liver in terms of how it may help to clear liver fat. And so when we go back to kind of the main question for this section, you know, which of the following is the best explanation for the gentleman who's concerned that these drugs are addictive and stopping them will cause him to regain most of his weight. What we see is it looks like the majority of people are answering B, while weight regain can occur if the medication is stopped, this reflects the chronic nature of obesity rather than dependence and continued treatment may be needed for long-term weight management. You know, really that's pretty much on point there. And so we have that explanation there and the rationale, and I think we've gone through it there. If anyone has questions, please drop them in the chat and we can address them at the end. So we're going to move on to case three, where now we have a 38-year-old lady with BMI of 34, so class one obesity, and she has PCOS, polycystic ovarian syndrome, and she's considering starting an obesity medication. She's excited because she says, I heard this medicine will make me lose weight quickly without having to change my diet. And so this may or may not be something you hear people talk about in clinic when they come to see you. And so which is the, following is the most appropriate response to set a realistic expectation for this patient? Is it that anti-obesity medications were independent of lifestyle change, so she doesn't need to modify her diet or activity to see results? Is it B, since weight loss is entirely dependent on behavioral behavior, medications don't provide any significant benefits beyond what lifestyle changes alone can achieve? C, she should expect to lose at least 50% of her excess body weight within the first three months of treatment? Or D, while obesity medications facilitate weight loss, they're most effective when combined with lifestyle modifications, such as healthy eating and physical activity to optimize health outcomes. And so I'll kind of let that kind of cook for a second while the audience kind of answers the question, how do you guys approach this when patients come in wondering, well, in addition to this, do I need to make any changes? I mean, I think about the last time I prescribed a statin, I probably did not spend very much time talking about saturated fat intake. What kind of input do you think we need in terms of adding in lifestyle support to prescribing obesity medicines these days? I know from my standpoint as a pharmacist, like I'm educating them that how these drugs were studied were as adjunct and added to lifestyle modifications. So that is the foundation for then sustainability as we've heard before in our panel discussion. And so this is not a substitution, this is not a quick fix. We still have to talk about how to make healthy choices and have those behaviors instilled to have further success. And again, it goes back to the foundation. Yeah, I think it's definitely kind of a yes and, it's kind of working out what is the right thing for us. I think the average person who comes to an obesity program or comes to an endocrinologist to talk about weight has likely tried a variety of different, yeah, it's called lifestyle-based interventions, be it an online program or behavioral health app or tracking application. And so just to suggest to them, like it's a novel thing, have you thought about walking 30 minutes, five days per week? They're like, I've lived with obesity for 20 years, of course I've thought about this. And so I think we need to kind of get beyond the house wine of suggesting something that's really obvious to our patients in order to engage them in treating what is a complex disease and also to improve their health long-term. And I think what we need to acknowledge is that obesity is a dysregulation of a very complicated energy balance system. And I heard Donna Ryan say one time, everyone thinks you're smarter when you throw up a picture of a brain. So I decided to throw up a picture of a brain here, just really to emphasize that there's a lot of complex inputs from a variety of peripheral organs, such as the adipose tissue, our gut, our pancreas, that are spewing a whole host of not just hormones that are acting locally, but also systemically and neural networks too, that help to regulate appetite and energy balance. I do not see the words willpower anywhere here. And so we need to acknowledge the complex biology that goes into energy balance, that's more than just making food choices and tracking what we're doing. There's been so much in the news and especially my social media in the last year or two with regards to body composition changes. And I think a lot of patients come into the office saying, I thought about this, but I don't wanna lose my muscle mass. This paper is a composite of some of the body composition kind of trials or sub studies from clinical trials that suggest that weight reduction with these agents, and here we have retrotrutide, which is the triple agonist, GIP, glucagon, GLP-1, with semaglutide, with the dual agonist, terzapatide, GLP-1, GIP, suggesting that about 25 to 39% of the weight loss is fat-free mass, so non-adipose tissue. But what it also shows is that 61 to 75% of the weight loss is adipose tissue. And so it all depends, are you a glass half empty kind of person? How do we look at this data? Do you have patients come into the office saying that they're worried about losing too much lean mass? 100%, I think that's one of the most popular, information that they're getting. The more patients using it, because it's been more popular, these medications and weight loss, more people using it. My neighbor is losing too much weight, or he looks like he's weak, or he doesn't look healthy, and I don't want to lose my muscle. Definitely that's one question that is recently being more asked in their clinic. But I think it's like you said, we need to understand this is a medication that is not related only for weight loss. We need to see an overall health of the patient. And the reason why we're prescribing it is to impact the health, and not necessarily the weight. Absolutely, and it all depends on what health means with regards to body composition, right? And I'll put this up here as an example. So when we look at the DEXA sub-studies in the Terzapatide CERMAT-1 trial, so people without diabetes and obesity who were treated with Terzapatide, and we look at the body composition changes from baseline to seven weeks, what we see is kind of a baseline body fat percentage of about 48%, which drops to 40.8%. So a 7.4% reduction in that. We also see then a relative kind of shift in the proportion of fat-free mass, right? And so we're like, well, that sounds good. But then when we flip to the right and we look at absolute change, what we see is a six kilogram reduction then in muscle mass or lean mass as part of this. And we're like, ooh, well, maybe that's not good too. And I think this is really challenging when we have a diversity of patient populations we serve, right? And so the question is, is this important? Is it meaningful? How should we even assess this? Many of us in our offices will have some kind of a body composition scale, or if we're kind of doing things differently, we may be measuring waist circumference or other kinds of ways in which we can infer body composition or other changes. I think personally, one good kind of way of looking at this is trying to assess patient function. And while it may not be practical in offices to be checking kind of hand grip strength or other kinds of measures of function, asking patients how they're doing in terms of strength and function, taking that kind of history can be very meaningful. Some studies would suggest that even though there was an overall reduction in lean mass, that there's improvement in muscle quality and function. That's a nice narrative I like to hold on to sometimes. But I think asking your patients, especially those who are at risk, tell me how things are going. Are there things that you can't do right now that you were able to do? What's your energy level like? Can be really meaningful ways of helping to assess how people are doing as part of this journey. Do you guys have any functional assessments or questions that you currently do in your practice to kind of see how things are going beyond the weight change? Usually asking about their energy levels and just exercise endurance, how is that improving? And also in regards to their biomechanical issues of being able to move around with less pain and decreased shortness of breath, those types of things. There are, we'll get to some of the questions and the comments in the chat in regards to that as well. Okay. And so when we kind of look at this, you know, we touched on this before. Dr. Chadha kind of stated, you know, talking with patients about, you know, bariatric recommendations when they're starting obesity medications. I showed a figure that suggested, you know, the magnitude of weight change that we see with these newer agents is kind of approaching that of bariatric surgery. When we think of our patients who are going for bariatric surgery, there is a kind of a course, a care pathway outline with regards to what needs to be done prior to surgery in terms of education, what needs to be done during or post-surgery with regards to nutrition supplements, micronutrient, diet, everything. There are care pathways, but that doesn't really exist for people on anti-obesity medications. And so there are several kind of consensus, if you will, or kind of guidance documents or review articles, narrative reviews, mostly to talk about evidence-informed suggestions for what people could do when they're on this. This is a paper that suggests kind of, you know, appropriate kind of calorie intake goals, which often err on the side of caution in terms of calorie intake. And many of our patients will likely report eating fewer calories. But the question is, you know, how are they doing when it comes to kind of calorie intake? Protein is something that many people talk about, and it's always kind of challenging sometimes to work out, well, should I do grams per kilogram for their current body weight, their ideal body weight? Where am I going with this? And I think many of us in this space will use broad recommendations so that we don't get caught down, caught up in kind of the process of somewhere around 60 grams of protein per day or 60 to 90, depending on the body weight of the patient. But of course, we need to acknowledge that these goals may be different if there's underlying chronic kidney disease or liver disease or other conditions where the patient may require different protein intakes. We need to emphasize that carbs are not evil and that there are healthy ways to incorporate carbohydrates into our lives, including those that are kind of more complex or as a vehicle for fiber. And many of us, you know, do not eat enough fiber. And you kind of look at recommendations for men, 30 to 40 grams of fiber per day, that's definitely impossible for me to hit on an average day and when people are on a calorie reduced diet, looking at, well, what does that mean? Maybe 14 grams per thousand calories per day can be one way of looking at it. When we think about fluid intake, it's important to make sure our patients stay hydrated because when you decrease their appetite or induced satiety, sometimes their thirst goes down too. And those of us who live in warmer climates, such as Texas, where I'm at, it can be really easy to get dehydrated in the summer, especially people who are doing outdoor activities or if they're drinking alcohol or things, it can be easy for people to get dehydrated. And if they're on blood pressure medicines, we need to make sure that they're getting adequate hydration, their medicines are being adjusted appropriately so we don't get into trouble. And so kind of a quick and easy rule is somewhere around two to three liters of water today, but of course that's gonna vary based on do they have a history of heart failure or kidney issues or other things that we need to be mindful of. You know, focusing in on avoiding things like sugar-sweetened beverages, alcohol and caffeine can be one approach, but moderation's key. I would hate if someone tried to limit my caffeine intake, right? And so we need to work with our patients on what is a healthy balance for you? There's controversy about vitamins too. It's like, should people take a vitamin? I mean, bariatric patients take a vitamin. Should someone who's losing bariatric amount of weight take a vitamin? We don't have good evidence. The way I look at it is that, you know, people who are living with obesity are at risk for nutritional deficiencies. Making sure we focus in on diet quality or dietary quality can be very helpful as part of this. But I'm also a paranoid person. I'm like, well, a multivitamin may not be a bad idea, particularly one that contains iron, especially for menstruating women, can be a way to avoid nutritional deficiencies, especially if there's some there at baseline. Again, we don't have great guidance with regards to should people be on supplements like this, but it's important to acknowledge that maybe it could be. But if you have baseline nutritional deficiencies, it may not be sufficient. Using something like a MyPlate method, for example, can be an easy way to help patients to conceptualize what does it look like to eat like this, right? In terms of protein, kind of starches and fruits and vegetables, discussing kind of fluids, especially if people are having GI symptoms, how much should they eat? What's an appropriate amount for them? How quickly should they eat? When do they listen to their body and say, hey, I think, you know, I'm satisfied and the meal's done. There are a lot of nuances to providing nutritional guidance with this. Life is real too. Talk about options like dessert options, snacks and other things that are helpful and supportive to your patients. Don't say, well, you shouldn't be doing that. Aren't you trying to lose weight? Again, don't come for my caffeine and don't come for my snacks. So I want people to have appropriate options and healthy, realistic conversations. I tell my patients, you know what? I'm shooting for practical non-perfection because many of our patients are leading busy lives. They've got kids, they're running around, they're doing work travel or food and interaction with people is part of their social life. And we need to make sure that we reinforce that this is part of your life, not to replace parts of your life, right? We talked about diet quality is something that's important for people on this journey. And we should really not focus in on a restrictive type diet of don't eat this, don't eat that, but let's work on the right proportions of things to both provide you with the weight and cardiometabolic health outcomes that you want, but also to provide you with the diversity of things. It can be challenging for people to eat nutritiously in a very balanced way, especially during dose titration, when they may have experiencing some of the GI side effects and consequences of finding the right dose, finding the right portion sizes, considering when to provide nutrition supplements. We talk about good days and bad day experiences with our patients on maybe, you know, when you're doing dose titration, you're having kind of a not so great day from a symptom perspective. Let's talk about how you're gonna meet your fluid requirements, your protein requirements and other things on lower stress foods for you, such as, you know, protein shakes or other things like that and working out, well, is this happening more often than not? Do we need to talk about a dose reduction? That's why this is part of chronic care that requires patient engagement and discussions, because we shouldn't just conflate access to drug with access to obesity care. We need to talk about this. We need to talk about how patients are accessing these medications to make sure they're seeing a clinician who's experienced in treating obesity, who knows how to prescribe the appropriate treatment for them, who knows how to integrate lifestyle modification as part of evidence-based therapy, and who's not just gonna work on prescribing them the highest dose available. The goal of treating with obesity medications is not to get people to the highest dose as quickly as possible to lose the most weight. It's to find the right dose for them that's going to improve their health, and that involves education around how to provide your body with appropriate nutrition that's not gonna exacerbate some GI side effects. It's gonna be talking about what is the dose escalation that's right for you? This is not a clinical trial. You do not need to increase the dose according to the product insert. You can increase the dose according to how well your patient is doing, and if your patient is not doing well on one agent, consider switching to an alternative one if this is not the right one for them. They work in different ways, and they have different levels of tolerability. Consider the use of over-the-counter medications if patients are having significant nausea, but also think, hey, is this not the right dose for them or maybe not the right med for them? Think about something else, okay? Because there are a variety of different ways to approach this, and it's better for patients to be on an evidence-based therapy that's providing them with benefits rather than trying to race them up to the highest dose and they need to stop it. It's important to look at this in terms of multidisciplinary care. I like to look at the primary care clinician in the middle who really should be kind of coordinating subspecialty care with people like us in the endocrine sphere and in terms of kind of working with other specialists. So it's how do we kind of create the right support system where it's foundational for people to have nutrition and mental health care, which I think is really important as part of any chronic disease management, and then working out how do we coordinate with primary care around everything from blood pressure, medication adjustment, insulin dose adjustment, does the patient still need their CPAP? Hey, their FIB4 score was off. Do they need a fiber scan? Do they need a liver biopsy? There's so many things that we need to think about in obesity care. Again, it's not just about providing a script and saying, see you in six months. Let's hope you do well. What we're doing is we're looking after people and working on improving their health. So to get back to our case here about not requiring kind of additional lifestyle modification, it was kind of a facetious question. I think you guys will all get the right answer with regards to this. Which of the following is the most appropriate response? And what we'll likely see is while obesity medications facilitate weight loss, they're most effective when combined with lifestyle modifications such as health eating and physical activity. And we talked a bit about supporting with nutrition, getting the right amount of protein, physical activity, all of the things that decrease loss of lean mass as part of a weight loss journey is so important. And so that's that there. And so thanks everyone for kind of listening to my TED Talk tonight. What we're gonna do is look at what kind of questions we have in the chat and try to address some of these within our time limit. What I'm gonna do is ask our ACE facilitator to kind of put the hook out when we need to wrap up, but I would like to address one or two questions before we have to wrap up from a time perspective. And so we have kind of a few kind of questions. Do you believe the more receptors are blocked, the more effective? So kind of the question is, do we think that kind of a double agonist is better than a single agonist and a triple agonist is gonna be better than all of them? I think it's too early in the day to kind of say that the greater number of agonisms or antagonisms will bring about the best results from a weight perspective. The slide I showed with regards to kind of the different organs which are impacted in terms of activity will suggest that there needs to be a more nuanced approach to obesity care that looks beyond weight reduction to the cardiometabolic outcomes. And so I think we'll need to kind of see what the clinical trials show with regards to outcomes. There's another question. Do you believe the GIP blockers and GIP agonists combined in the future to manage obesity? So there are kind of agents on development. We've talked about a GIP receptor agonist, but there are also GI receptor antagonists that are under development for treating obesity and cardiometabolic issues. And so that goes to show that we don't fully understand the biology of these agents. And there may be that chronic agonism leads to antagonism and down regulation of receptors. We don't fully know, but more to come on that space. And what one person said, I see recent data suggesting that despite fat-free mass decline, it's not specifically measuring skeletal muscle mass and actually the muscle quality is improving any input. So yeah, I made that comment in passing that some studies suggest that there's an improvement in muscle quality there. And I think that's gonna be challenging for us to assess clinically. And I think, we're not gonna be able to do muscle biopsies on patients in the clinic and working out for yourself as part of your clinical workflows, what is a meaningful question with regards to physical activity, function, energy levels that's impactful here? What are your red flags for saying, hey, I think I need to refer this patient to a dietician for augmented nutrition support. I think this patient may be losing too much weight too quickly, we need to back off on the dose and foster appropriate healthy weight and cardiometabolic improvements rather than just rapid weight loss. There are a variety of different things that unfortunately we won't have the time to approach this evening in our talk. And so in the interest of time, it looks like we need to wrap up now. And so I'd like to thank my co-hosts this evening, Dr. Chadha Moghulian and Clemens for their wonderful insightful comments and for being with us this evening. I'd like to thank the audience for their wonderful questions. It shows that you guys were really paying attention tonight which makes me very, very happy. Please tune in for the remaining webinars in this series as well and the other great content that ACE is creating in the obesity space. So thank you everyone for attending tonight. Look forward to seeing you all again in the future. Thank you.

obesity

medications

lifestyle changes

GLP-1 receptor agonists

chronic treatment

weight loss

metabolic health

emerging treatments

holistic approach

patient perceptions