All right, welcome, and thank you for joining Reframing Obesity Treatment Series, Addressing Stigma, Myths, Misconception, and Patient Concerns. I am Maria Mogollon, and I'll be moderating this session, Optimizing Care, Managing Concerns, and Improving Adherence. We are fortunate to have Dr. Jennifer Clemens leading today's case-based discussion with Dr. Jaime Almondos, Monisha Chadha, and myself, adding insights throughout the session. Before we begin, I'd like to invite each of our faculty member to briefly introduce themselves. Why don't we start with you, Dr. Clemens? Sure, my name's Jennifer Clemens. I'm clinical professor and director of pharmacy education with the University of South Carolina and College of Pharmacy in the upstate of South Carolina. Dr. Chadha? Hi, my name is Mona Chadha. I am an endocrinologist and diabetes educator. I'm with the Ochsner Healthcare System in South Louisiana. Hi, everyone, I'm Jaime Almondos. I'm an associate professor at UT Southwestern in Dallas, where I'm also medical director for the Weight Wellness Program. It's great to be here. And I'm Maria Mogollon. I'm a foreign physician in total medicine, specialized in diabetes and obesity, and an APRN here in United States, also specialized in obesity and diabetes. So, but before we begin, here's how the format will work. As cases are presented, polling questions will appear in your screen. Please take a moment to select your response. Once the polling close, we'll display the results and discuss them. We encourage to participate. Feel free to type your questions on any aspect of the presentation into the Q&A box at any time. We have reserved time at the end of the presentation to answer your questions. With that, let's get started, and I'll turn it over to Dr. Clemens. Well, thank you. It's a pleasure to be the lead of this discussion tonight. Before I begin, I do want to mention I have a few disclosures, which are listed on this slide. Now, the main objective for this evening is to really kind of dive into some of the concerns that are heard in clinical practice, particularly about obesity pharmacotherapy, and this would include side effects, muscle mass loss, and access barriers. So, what we're gonna do over the next 50 minutes is, again, we'll have some cases, like you heard where you will poll, but I also have some questions planned for our panelists to really try to cover as much as possible in this period of time. But again, feel free to put in your comments in the chat, and we'll get to your questions at the end. So, we will open up with a case, and this first one is about optimizing care by managing safety concerns before the initiation of pharmacotherapy. So, this is a 36-year-old woman with a BMI of 35 who will be initiated on a GLP-1 receptor agonist. So, one thing to keep in mind is that she's heard about nausea and vomiting with this class of medications, as well as acute pancreatitis and gallbladder disease. So, currently, she's already been making some lifestyle modifications and changing her behaviors to lose weight, but the question really is, which of the following is the most appropriate initial step when a patient expresses concerns about potential side effects with an anti-obesity medication or, as I like to say, obesity pharmacotherapy? So, this particular case and question does have some long answers, which may have already popped up for you, and you started reading ahead of time. So, I'll just pause to give you a few more seconds to lock in your answer before we have some discussion and then reveal the correct answer. Now, before we really discuss everything within that case, and we may only get to some of it because we'll have some additional cases and then slides related to the side effects, whether they're common or they're rare in some cases, I first wanted to bring up as a reminder the 5 As. This is a three-part webinar series. So even in our first webinar, we had discussion amongst ourselves about the 5 As and using person-centered language for communication. So this is just a reminder that regardless of where you practice, we do have a structured framework that we can rely on when it comes to obesity education. However, I wanted to also mention that when you look at those particular verbs that are used, there are some publications like this one that has proposed maybe an update with the terminology. So you can see in certain steps within this process that the A is actually eliminated to then change the verb to something that's a little bit more aligned with patient-centered care but also can be a collaborative approach because of the shared decision-making that goes into it. This particular illustration is just for each consultation, and I would encourage you to look at the publication because it has another image that really emphasizes that when we discuss obesity, it's behavioral changes that will happen long-term. So over time, and we have to keep that in mind, and it will also be at the pace of that individual we're working with. Now before I open it up to our panelists, I did want to bring attention to the pillars of comprehensive care when we look at obesity management from the Obesity Medicine Association. So since we're talking about person-centered care, it's still important we rely on the pillars within this because it is evidence-based, comprehensive to lead to that long-term success with weight management. So the four pillars listed for you, as you can see, would involve nutrition, activity, behavioral modification, pharmacotherapy, and surgery. Our emphasis tonight when we talk about, you know, the side effects, loss of muscle mass or even access will all be centered around pharmacotherapy, which again is just one piece of this particular illustration, again, showing comprehensive care. So before we kind of go farther and reveal the correct answer to this case, I wanted to ask our panelists just a question to gather thought. So you know, what specifically do you kind of discuss before you initiate a GLP-1 receptor agonist? Do you focus on just the common adverse events, or do you also mention other things like acute pancreatitis, acute gallbladder disease? How much do you share, and do you have any tools that you use in practice, like a handout, a checklist, or something built into your electronic health record? So I'll kind of open it up, and anyone can start us off on this one. Dr. Chadha, do you want to start? Sure. So generally when we're talking about using various medications, I'll ask if patients have ever been on anything before just to see what their experience has been when it comes to initiating the GLP-1 receptor agonist treatments or the GLP-1 and GIP combination therapy. What I try to establish is what the patient's perceptions are, because there can be a lot of patient-centered bias and misinformation that they might have read. Some people feel that these things are sort of like the magic bullet and the answer to all their questions, which we know are not the case. And I also kind of establish what their current eating habits are, because I let them know that if they're eating larger portions or eating frequently throughout the day, that might increase the risk of developing some of these GI adverse effects. So again, with that shared decision-making model, I try to establish what the patient's perceptions are initially, so I make sure that I answer the questions that they have, and then speak mostly about the common side effects. I do have a handout that's based on the package insert, translating that into layman's terms that I provide to patients in my clinic. Dr. Almendoza? Yeah, I think there are a lot of different ways in which you can approach this. When we talk with patients about potential side effects, I think it's always great to kind of start with how do these medicines work, and talking through kind of where ingredients come from, how this is kind of leveraging a natural system in our body, that these are naturally occurring peptide proteins that kind of are released in response to eating. It can help people to understand, well, how is this going to work in my body, and how could it help me to modify my interaction with my food environment, helping people to understand that there's going to be a reduction in appetite. In addition, there's going to be changes in kind of the speed at which our stomach empties, and it's going to help us to feel satisfied with less food for longer. This really sets people up for success. I'm not sure about you guys, but I've had many patients who said, you know, I got really anxious when my appetite went to zero. I've never experienced that before. Helping people to know what to expect, helping to plan or contextualize the nutrition recommendations about planning to have smaller portion sizes, for example. Once they understand how the medicine works, it helps to contextualize, well, why is this important, and why might this change over time as the dose increases? Helping people to understand the dose-dependent effect that it can have on appetite reduction, and other changes can really be helpful. We talk through, you know, the potential risks that we should kind of cover from a medical legal perspective in terms of kind of potential risk for pancreatitis, label warnings with regards to thyroid cancer, things that are important as part of comprehensive care with these molecules, but really hitting the high notes on the gastrointestinal disturbances that are most common for people, helping people to realize that some of these effects can be mitigated by modifying strategies in terms of appetite. So things we like to explore with patients are, what does hungry feel like for you now? How do you know it's time to eat? What does full feel like for you? How do we know that the meal's done? Can help people to be more aware or aware in a different way with regards to where they're at, with regards to hunger and satiety, and how these can be tools to help to modify that, and how to be aware if we're on too much of a good thing also. Remember, we've talked about this in other episodes of this series, that the goal is not to get people up to the highest available dose, but to work on finding the right dose at which people are able to modify their interaction with their environment in a way that permits persistence of an evidence-based therapy that helps not just to decrease body weight, but also improve health. So I think there are a variety of different ways in which we can approach this to make sure that we are kind of covering kind of big ticket things that need to be discussed from a safety perspective, but also the practical side of things with regards to how do these medicines work, how can I integrate this into my nutrition plan in everyday life, and how do I avoid side effects, and when to call the clinician to say, hey, I think I'm on too much of a good thing, or I think I'm ready to go to the next dose. Great. Well, for the sake of time, let's move on, and we'll come back, obviously, to all our panelists for thoughts and comments. I did just want to share this as kind of while we, this is just the first case. We have other cases. We're going to focus on the common adverse events, but we will dive into some other safety considerations and the evidence behind that. It may not be much evidence, try to pull the most recent, because we could really spend an hour probably on each of these safety considerations when we talk about this particular class of medications, for example, and so we'll definitely have time to bring those up for our panelists to comment. So, if we could see the poll, or does anybody want to guess from our panelists what was the correct answer? I do see the poll now, where majority, 92 percent, picked B, and 8 percent picked A, and so for everybody participating this evening, B is the correct answer, so just trying to refresh and bring out some of the information we talked about in the first and even the second webinar within this series, and we have to have that discussion for shared decision making moving forward for the individual to have success that really will allow us to build trust and improve adherence to therapy, again, by providing that education to the individual and address their concerns, so I liked all the strategies that are currently being done by our panelists in discussing that. Let's go on to the second case, which is more of optimizing the care by managing the safety concerns after a dose escalation, so for this individual, they're 47, BMI is 32.5, and they're supposed to start the 2.4 milligram dose of semaglutide after titration, so what you see here is that after she initiated semaglutide, she was educated on the GI symptoms or adverse events that could happen, and at month two, she reported mild nausea and encouraged to eat smaller meals, and then at month four, while she made dietary changes and adjusted the frequency of her meal, the nausea continued to worsen, actually, and she had occasional vomiting with that, so here we are today trying to go up on the dose, and she's still experiencing nausea, intermittent vomiting, and the early satiety, but she's reluctant to discontinue because she's seen the significant weight loss, so while she's having side effects, she'd like to stay on it, so from that, after reading that, the question is, what is the next best step in the management of the GI symptoms that this individual is experiencing with the pharmacotherapy, so should we continue at the current dose and add generic Zofran as needed, reduce the dose to a previously tolerated dose and reevaluate, discontinue the medication and initiate another obesity pharmacotherapy, or maintain the current dose and reassure her that these symptoms will resolve over time, so I'll give you just a few more seconds to log that in, and while you're still entering in your answer based on this case, I am going to turn to our panelists, so you just heard before, in a case before the medication was started, that there's some education that's involved, but I'm kind of curious, even though the next slide we see, I have, you know, what strategies do you put into place, we already heard about portion sizes and explaining the medication, you know, so they have a better understanding and then working with them, but I'm curious from the panelist's point of view, once you kind of do that, what do you focus on next after portion, do you focus then on what's on their plate, and I'm also, as a pharmacist, trying not to add more medicine, so at what point are you like, I need to add another medication to help alleviate some of these gastrointestinal symptoms, and then lastly, tell us, you know, have these strategies really improved tolerability and adherence with patients at your own practice? Yeah, Dr. Kamens, I completely agree, we need to understand that these medications are, have severe, sometimes side effects, gastrointestinal side effects, and could compromise the adherence to the treatment, so I think the first thing I do if I'm in front of a patient that could be a potential patient that might have side effects and severe side effects, I address that before even starting the medication, we need to classify or we need to identify what patient are we treating with this type of medication, if this patient previously has any sign of symptoms, gastrointestinal sign of symptoms, also like Dr. Shada mentioned, what type of food this patient, is he more type of Hispanic type of food, or depending on the amount, and not only the amount, the type of food also affects the way these patients react to this medication, so if we have a comprehensive before starting this type of medication, we might prevent side effects, or at least severe side effects, and definitely if we're going to increase the dosage, and we might be having a side effect, address this before adding this extra or adding or titrating up the medication, I will not recommend adding another medication to treat the symptoms, I will definitely decrease the amount in case this patient presents symptoms, we want this patient to adhere to the treatment, but at the same time without any side effects, or at least the minimum side effects. I think a discussion regarding the shared decision goal of starting the medication, because ultimately we want to take a holistic approach and improve the overall health of the patient, improve their cardiometabolic risk factors, the biomechanical sequelae from obesity, just their mental health, all of the issues that can be related to a patient living with obesity, and so if a patient is developing progressively worsening gastrointestinal side effects, it might be an opportunity to pause and say, how are we using this tool? And so potentially reviewing how much protein, how much hydration, fiber, you know, sometimes people use digestive enzymes to help improve tolerability, but I think ultimately to come back to that initial discussion of how are we using this tool to improve their overall health is important. Excellent. Well, I did want to share with those listening, you know, a couple of papers that are out there that could provide guidance for you in practice. So this first one really came from a consensus of endocrinologists, nephrologists, primary care providers, there were cardiologists, all with the focus that they have clinical expertise in helping people with diabetes and obesity. So they're very familiar with the management, and he even used the GLP-1 receptor agonist or the dual receptor agonist. And so the whole point was to kind of come to an agreement on what should be some patient education provided to help minimize the frequency and intensity of the adverse events related to this class of medications. So based on this illustration, you can see that there's obviously education on dietary changes which we've heard. There can even be the flexibility in the dose escalation. So we even heard that earlier that we don't always have to seek out the maximum dose of that medication. We can slowly go up, doesn't have to be per the package insert, right? It's based on that individual. But they also then provide some guidance on symptomatic treatment, particularly if it persists. So you can see kind of here towards the bottom, you know, what may be suggested if they're persistent or severe and when to seek out attention from the provider. And of course, you heard that from our panelists as well this evening. There's another paper that was published, Individuals Coming Together to Provide Their Expertise, not necessarily like a consensus paper, but they provided, if you've heard about it, the three E's. And so from that, you can see the first one is education and explanation, which we've talked about. This is really letting individuals know those potential adverse events, ways to minimize that through those mitigation strategies. So you've heard some of that already. They also recommend escalation to an appropriate dose. And so when you think about that, it's based on the person in front of you and not how we would generally treat, you know, everybody with this medication or per the package insert. You can even see in some of the newer evidence, like the Surmount 4 trial, for example, even 5, if we had that pulled up, they use the term maximally tolerated dose because it's based on response and tolerability. So you don't always have to seek out the maximum dose. But they do also, for their third E, have their listed as far as effective management based on the severity of the GI side effects. So what to do if it's short term and mild, what to do if it's persistent and severe. So the management is really kind of a stepwise approach, you know, in terms of what could be put into practice. So again, not a consensus paper, but something that they probably developed thinking it's fairly easy if you think about three E's, and this is a way to remember it for clinical practice and putting, you know, again, this kind of severity-based approach as something that could be useful, again, in clinical practice. But before we go on, I did want to ask our panelists, so we've heard a lot about the strategies, but one thing is that we can read a lot of papers or we can think generally, but I wanted to kind of ask for your opinion regarding maybe certain patient populations. You know, I've encountered people that have had eating disorders and that there's some evidence to show that these medications could help, but then you get cautious with it based on knowing they have an eating disorder. When they're over the age of 75, I get concerned because of maybe dehydration down the road and then volume depletion. So I'm just kind of curious your thoughts in certain patient populations and using GLP-1 receptor agonists, like eating disorders, older individuals, what if they already had a prior upper GI, you know, event, you know, but it's been resolved for a long period of time. How do you handle these or do you even recommend them? So I'm just curious about your thoughts. I think there are a lot of different niche populations in whom we should have kind of special precautions, I guess we could call it, or just maybe closer attention with a different lens. We can start with the older population. I think this is a very kind of topical, I won't say issue, but perhaps topic of conversation with regards to older adults, for example, with a history of atherosclerotic cardiovascular disease who may be starting somaglutide 2.4 for cardiovascular risk reduction. There was a recent analysis in one of the Surmount papers looking at changes in body composition by age, showing that there were kind of similar reductions in lean mass across the different age groups. I think that had been a kind of a concern with regards to older adults being on medications like this. That being said, you know, we lose about 3% of our lean mass every year from age 40 onwards. And so while it may look equitable, I think the important thing is how do we assess patients like this in clinical practice? I think the challenge is that many of us may not have body composition machines within our office to be able to do this. But beyond that, changes in body composition don't always reflect changes in function. So it's really important for us to have ways in which we can ascertain this by history in terms of asking what people are currently doing, what they're able to do, assess that iteratively to make sure that they are not kind of losing functionality or gaining frailty or having falls, making sure that we assess nutritional status adequately at baseline, and to make sure that people are kind of assessing or making sure that they're meeting their nutritional needs, working out for that individual, at what point should you give me a call with regards to you are losing X amount of pounds per week beyond kind of what we've agreed upon, or you're experiencing symptoms that could be concerning for dehydration, for example, if we're talking about older adults who may have inherent frailty if they're post-CV event. Anything else to add from our panelists before we go on? Okay, go ahead. I actually have a conversation with women of childbearing age for whom I'm prescribing these medications, and not to be intrusive, but to gather information about their plans for future fertility and the potential side effects, et cetera. And even if they're not desiring future fertility, if they're on oral contraception, how, as the dose is being escalated, the need for additional contraception may be required because of the effect on gastric motility and absorption of those oral contraceptive medications. So the incidence of type 2 diabetes is becoming younger and younger, and so I think having a conversation with patients of this age group as, again, to shared decision-making for health goals, and especially for those women of childbearing age. Yeah. Well, if we could see the poll before we go on related to this case. So it looks like no one chose C or D, which was discontinue and initiate a different agent for weight management, and then no one chose maintaining the dose, and then just reassuring them that these would go away. So we've got a majority picking reduce the dose to the previously tolerated dose and reevaluate, and 15% saying they would continue and then add that generic Zofran on as needed for nausea. So for us, I think you've kind of heard that there's different strategies, of course, and I can definitely understand with A, that this is an individual that's kind of experienced the GI side effects with each dose escalation, and they've gotten worse. But maybe the best approach would be to back down to what she was on previously. We still want to use the medication given the benefit of cardiovascular risk reduction. So we have to take that in mind as well, but maybe reducing the dose will further help minimize the adverse effects. But I completely understand as well, these are just hypothetical cases. They're not real people that we're interacting with and having that conversation on what they want to do. But obviously, there's multiple options depending on what you want to choose. Now before we go over case three, I did want to touch on some other evidence with the GLP-1 receptor agonists. I am going to ask a question to our panelists because I'm a pharmacist. So as the medication person of the team of the endocrine care team, you know, I think we obviously analyze every medication and we try to know as much as we can from the package insert and all the studies. And you know, we still see the boxed warning of the risk of thyroid C-cell tumors with the long-acting GLP-1 receptor agonists. And when you think of that, it's animal studies in rodents. When you pull randomized controlled trials, as you see here, it's a rare occurrence for those receiving the GLP-1 receptor agonists. So if this is like a possible but not really verified risk or association with these drugs and this type of cancer, I'm just curious from our panelists' stand, you know, have you seen this in practice? Have you had to do any further monitoring evaluation? But then I also would like to pick your brain, like, do we ever assume this boxed warning will go away with the medications if we're not seeing it in humans? I want to say this also, this type of cancer is not the most common one. So probably that also play a part there that we don't see patients frequently, at least not in my experience. So but we definitely need to address patients with thyroid cancer and especially if in that category, addressing the potential effect of using this type of medication. If that's positive, I will definitely not prescribe it, is my personal opinion. Because of that, unless this will go away in the future, that might be, I really want to know the answer of that question too. You know, I think that's a really complex regulatory question that I think none of us are going to be able to answer with any certainty with regards to that going away. I think the most kind of common thing that we see in endocrine practice are people who referred in with a history of papillary thyroid cancer, and they're wondering, is it okay for me to take this? And I think, you know, reassurance is appropriate there. And then trying to work out when someone says, well, I think I have a family history of thyroid cancer. And then it's important to get the records just to make sure that it's not medullary thyroid cancer. They don't have a familial syndrome that could predispose them to this. And so I think there are a variety of different ways in which we can approach this in clinical practice to kind of reassure patients and to kind of find people who may be truly at risk in whom they should not be prescribed. It's rare, but we do work. Some of us work at academic centers where we will see patients with a personal or first degree relative history of medullary thyroid cancer or multiple endocrine neoplasia. And so it's appropriate to educate them with regards to screening for additional cancers that they may be at risk for themselves, but also which medications may not be appropriate for them, such as those. Absolutely. I'd also like to add, I mean, there've been some anecdotal reports of incidents of papillary thyroid cancer in patients on GLP, but with the understanding that they're under increased surveillance. So it's not necessarily increasing the rates of papillary thyroid cancer. And I don't know what your experience is, but I know that with our EMR on Epic, if I'm prescribing a GLP-1 agent to a patient with papillary thyroid cancer, a big red loud error or alert will come up from the EMR stating that there is this evidence in patient with medullary thyroid cancer, and then in very small light font underneath that the patient has a history of papillary thyroid cancer. So I think it forces us as healthcare professionals to know our patients and know their pathology and know whom we're prescribing these medications for. That having a risk of papillary thyroid cancer is not a hard stop, that these medications can be used safely in these patients. Yeah. From my experience in working in different electronic health records, and most recently Epic, we don't have something that pops up like that, but, you know, it's a good thought moving forward. So I appreciate that. I wanted to turn everybody's attention and just briefly show like the risk of pancreatitis. So this is really like a cohort study for those that took a GLP-1 receptor agonist, those that did not, matching them, obviously, given that it was a cohort study. But the risk of pancreatitis over time is actually lower than the lifetime risk overall. So when you think about using the medications, I do think I've had a lot of questions or even people stop me at certain points of education to be like, now I had a friend that had a had pancreatitis and they were on this drug. And we know that there could be a lot of different other reasons why they may have developed pancreatitis. But also I think that, again, this is education, maybe even with assessment, I know I've changed certain questions I ask when I look at response and tolerability, you know, being a little bit more specific, not just being general like nausea, vomiting, abdominal pain, but maybe asking where any abdominal pain may be, with or without vomiting, et cetera, before I myself would refer to a provider to then do the diagnostic test. But we, of course, want to be aware of this because it is in the label for the GLP-1 receptor agonist, as well as acute gallbladder disease. And so this was a systematic review and a meta-analysis looking at the risk with GLP-1 receptor agonist that it showed there was a risk, and in fact, it could be higher when you're on higher doses and you're on it for a longer period of time. But there's people or there's evidence, of course, and what I hear because I don't diagnose is that, well, when you have rapid weight reduction, that also could lead to gallbladder disease. So I'm kind of curious, this may be kind of an off-the-wall question, but is it, you know, which came first in this case, the chicken or the egg, right? So is it, is it the weight reduction leading to the gallbladder disease, if you see it, or do you think it's the medication or we just, we don't know, it could be a combination of both, right? So I'm just kind of curious from your point of view, because you guys would do more of the diagnostics than I would, obviously. I would say, again, this is a really challenging question where we're never really going to know people living with obesity are at greater risk for having gallstones, particularly certain race, ethnicity, and age groups. And weight loss is also associated with gallstone formation. And there are many people living with gallstones who are completely asymptomatic. And so there's a very kind of complex intersection here. I think the key thing is educating patients that this is a possibility, that they could experience abdominal discomfort and how to know when it's not kind of a, ooh, I feel a little over full and bloated versus this is a kind of postprandial biliary colic type situation or colic cystitis type pain for which they should seek medical attention. So I think, again, it's all part of that patient engagement, patient education intersection for making sure that we make people aware of the risks and when to call us. Yeah. And I do want to say from the systematic review and meta-analysis, we know that this sort of safety was not primary, you know, may not have been collected in all the studies, right? With all the medications. So it's not always the predefined safety outcome. I am watching the clock and do want to keep mindful of time. I did include some information. We know that healthcare systems and hospitals have changed their pre-op instructions and guided patients on the temporary hold on GLP-1 and even the GLP-1-GIP receptor agonists. You can see this particular illustration does compare to SGLT2 inhibitors because that's another class that would be stopped before surgery. So the concern is that there could be some remaining food contents and so that could lead to pulmonary aspiration. But I did want to mention it because this is something new that has been addressed when announced by the FDA and then added to all the labels. So it's something to be mindful of and know why those healthcare systems and hospitals may have changed their instructions. We have talked about drug-drug interactions. We know that oral contraceptives, particularly with trazepatide, is, you know, mentioned to be aware of because of the delayed gastric iftening being the highest after the first dose, the oral contraceptive would be changed to a non-oral contraceptive or the barrier method would be added. But then obviously there could be caution in general with any oral medications, particularly ones that require therapeutic drug monitoring if they are on a GLP-1 receptor agonist or the dual receptor agonist. So since we've already had some comments about that and with that added information, I'd like to just switch and get opinions on, you know, I get questions sometimes and I don't really know how to answer them because the evidence is kind of all over the place and more is coming out, it seems like, all the time regarding suicidal behavior and ideation. So I'm curious, from y'all's point of view, is this something you talk about or you monitor at the visits? You know, what type of screening do you do or proactive strategies do you have in place for patients that may be at risk? Just to kind of touch on kind of the concerns around kind of mental health from, I think it came up a couple of summers ago, you know, subsequent kind of large health system analysis have shown that there is no kind of broader association with declines in mental health, worsening depression or suicidality with imprudent-based therapies in those with and without type 2 diabetes when compared to other therapies within the class. I think what this points out to is kind of unfortunately just a lack of systematic mental health screening and care that many patients have. An inadequate acknowledgement with regards to the bidirectionality of mood disorder and depression and the association with obesity, including therapies that we use for depression, how they can facilitate weight gain, but the challenges that people who live in larger bodies face from stigma bias and a variety of different avenues. And so what I think this highlights is the need to appropriately screen for mental health challenges in all of our patients and to iteratively follow them if we have, if we see signals that we should be paying attention to and also checking with patients as part of their journey as part of routine health. And so that's kind of my thoughts with regards to kind of how I approach the kind of the concerns around depression or suicidality with patients. Absolutely. We touched on this somewhat in the first webinar and that we know that patients living with obesity can experience social isolation and depression and anxiety can accompany any chronic medical condition. So as the patients are being treated for obesity, are they now trying to navigate different social situations and different social cues? Are they getting different types of attention that they might not yet be capable of coping with? And so again, taking a holistic approach, we need to have these screening strategies in place. Well, I think the next thing we'll do, because those are, I mean, very much valuable information to add to this discussion as we kind of transition away from side effects to the loss of muscle mass, which was also touched on in our second series. So we may kind of quickly go over this because there's already been some discussion on it, but let's have a case in which you can pick what you think is the correct answer regarding a 60-year-old man that has a BMI of 34.7 and has started on a medication. He's concerned about potential muscle mass loss due to the medication while trying to lose weight, but does engage in resistant training once a week and eats about 60 grams of protein per day. So you have current weight and blood pressure. So what is going to be the best recommendation to address this patient's concern? Is it to discontinue the medication, so suggesting that, inform the patient that muscle mass loss is unavoidable, advise to increase protein intake and resistant training, or then recommend reducing the medication dose? So I'll just give you a few more seconds to answer. So, as we go on, I just wanted to show that there is a good publication that explains kind of the fundamental principles when an individual loses weight and how that can really impact body composition and the changes behind that. So we've already heard a little bit about that and also that not everybody may have this type of equipment to do or evaluate in clinical practice. I know that I have not worked in a practice that's had this capability to look at these changes, but it also shows you that there is some organ tissue involvement when you think about fat mass and lean muscle mass. So molecular within anatomically defined organs and tissues, and again, connected to fat-free mass, et cetera. But I really want to get into more like the recommendations because we have this long list, as you can see in the table, that includes what type of exercise, the frequency, the order, and even the load, repetition, set, speed, and rest periods, which I've mainly worked in VAs and family medicine offices could be overwhelming to some patients when they may get some of these recommendations. But I've also encountered with protein intake that the evidence sometimes varies. And so I summarized that on this slide where you can see that the recommendation could, again, vary in some of these studies. And we touched on this in the second webinar when we saw the nice publication and the illustrations that were published in Diabetes Care showing that there is going to be more loss in fat mass than lean mass. However, that lean mass loss could be equivalent to, I think, about a decade of aging. And so we kind of heard already that we lose that 3% over the age of 40 earlier this evening. But retaining lean mass during incretin therapy, so like with the GLP-1s and the dual receptor agonists could actually blunt body weight regain when the medication may be stopped. So I wanted to just pause here and get the opinions. You know, can you touch on if you do the body compositions? We kind of already mentioned not everybody has that, but specifically if you do this. But then also, do you have a specific recommendation for younger patients versus older patients when it comes to protein intake and any strategies behind that? I know for me, I've encountered some patients where they say it's difficult to get more protein into their diet, even when we start to kind of really dive down deep. And so really trying for these individuals, maybe even on low income, think outside the box. And that's from my experience, but I'm curious from your standpoint. Yeah, so definitely it's important to address this. I want to say that I focus more on the body composition, especially for elderly, more than 50 years old because of the sarcopenia, that's a physiologic process that we all are going through because of the same process of aging. So I don't think for the elderly, we definitely need to focus because this type of medication sometimes suppress hunger and patients can refer that they are not eating the entire day. And that could accelerate the process of the sarcopenia, addition to the medication and the appetite that is losing the patient. But for younger, definitely is another aspect because these patients are not affected as much as the elderly. So definitely exercising, weight training is very important and the consumption of protein will be part of what I discuss with my patients, especially more than 50 years old. Anybody else? We try to keep it simple from a protein intake perspective. I think people get hit over the head a lot with protein, almost to the point that you would think that we were living in an epidemic of protein intake malnutrition. Whereas I think for the average North American, we're really not in a hugely protein deficient state. I think when appetite is significantly suppressed and if you look at how some of these medications impact appetite, the way in which Kevin Hall studies have modeled this on 2.4 of SAMO or 10 milligrams of trisepatide, we're decreasing energy intake by about 900 to 1200 calories per day. And it all depends on what your baseline dietary quality is. So all that to say is assess for people where you're starting out at, what are your preferences, what are your concerns that you have around diet or intake or health conditions that may impact what we recommend from a protein perspective? Do you have CKD or liver disease where we may have concerns around what you're getting? Do you have vegan or vegetarian type intakes that may be a challenge for how you meet your protein unless you're more intentional? And then working out for people, if you are having a challenge doing that, how can we supplement your protein in a way that works for you from a logistic, a taste, a texture perspective, but then also from a GI tolerability perspective too. So a few different ways in which we can assess where people are starting off at, how they're doing and how can we best support them as part of the journey. Yeah. If we could see how people answered for this one, we can go through case four and wrap up here in about five minutes to take any questions that you've added to that particular part of Zoom. And so we see that 93%, or I can see that 93% chose C for this particular case. And so that is the correct answer that, and we've also heard some additional strategies this evening to try to get adequate protein intake and then the resistant training behind that as well. So instead of once a week, maybe a couple of days and then go from there. I did want to touch on a case for improving adherence and accessibility with these medications. So if you have a 35-year-old woman with a BMI that's 38, prescribing therapy reports significant improvement in weight loss, but struggles with the cost, works part-time, has limited insurance coverage, and you see other medications she's on. So I'm just curious if you pull in the most effective strategy for overcoming any insurance related barriers to getting these medications. So is it to recommend a supplement over the counter, provide them samples long-term, encourage them to seek coverage through their employer, or submit a PA request with supporting documentation? So I'm going to assume that this one is pretty straightforward and easy. And so I did want to mention as you continue to poll on this one, enter that in, is that it's kind of hard to really talk about this in depth because we probably see varying things depending on where we practice. And so access and affordability is always something that comes up. So I think there are various strategies to put into place to get coverage. But also we will see changes throughout the year. So I'll use ZetBound as an example with the moderate to severe obstructive sleep apnea. You know, if Medicare seems to be picking that up, but there could be other insurances that are not. So I have to think like for myself, if I've enrolled in my insurance in October, I really don't re-enroll until the next October, which then my insurance may pick it up after they evaluate it and potentially add it to formulary depending on the tier. So it is a little bit hard, especially as we see this new evidence, because we know it could change. But I did want to bring up an old paper. And so I know that this is old. This was published in 2012. But this was a survey to individuals living with obesity, and they really were asked based on specific things related to pharmacotherapy, like percent of weight loss, risk reduction, time to notice a change in their weight, how the medication was delivered, the safety profile, lifestyle modifications and cost. They were asked pretty much like what is the main reason they would be willing to pay for pharmacotherapy. And they really said that it's based on the percent of weight loss that they could get from that medication. It was also interesting that at the time, back in 2012, they would be willing to pay $10.49 in U.S. dollars per month for that medication. And I know that that is probably not the cost that we're seeing for some of these, right? And so I did want to mention that also in this paper, they said they would pay $30.70 more per month if it was a one pill per day versus a weekly injection. And also if it did not necessarily require them to make too many changes in their lifestyle modifications. So it's an interesting paper that I just wanted to mention, but obviously one too that's out of date. Especially as we look at probably quality adjusted life years with medications, pharmacoeconomic data, with anything that comes out and we see that it's not always fitting one pill per day. We're seeing injectables and we're going to have new orals that may have some administration restrictions on it and still be once a day. But we still have to pick the right medication for an individual, but also ensure that they can get it and it's affordable to them. So if we see the poll for this one or ICANN, I'll quickly turn it over back to our moderator for questions. And it does seem like 92% picked D, which was the answer that I'm sure we've all been through. I know that that's mainly how ICANN Assist is going through and helping fill out those PAs and providing the supporting documentation to get any medication for someone, particularly as that's important for them then to receive it and see the results. So I do want to thank everybody for letting me lead this. It's great to be part of this panel discussion and this is the last one, but I'll turn it over to our moderator to kind of take it away with any final comments and questions. All right. Thank you, everybody. Yeah, I do have two questions, Dr. Clement, but the first one I think is intended for ACE is how do we get our CMEs credit for three programs? I'm going to share information at the end for that question. And another question, is it possible to use in a patient with moderate ulcerative colitis, I'm assuming, treating moderate successfully with antiviral? So it sounds like the question is like they're successfully treated with therapy. They already take for ulcerative colitis, but they have moderate ulcerative colitis. Yeah. And I'll say from my experience, I've been mainly in family medicine, but a focus of diabetes and obesity that it's not necessarily sometimes the patients, but I have to work with the providers and there's some resistance because if they ask me a question, I don't have the evidence to answer it. Some of these patients were excluded in the trials and I just have to say like, I don't know. So I know that we do shared decision-making, right? And so we educate the patient to have a better understanding on what this medication does. But of course, when I work with providers, I'm going to get more of the evidence questions. And if I don't know, I don't know. And so sometimes in this situation, we have not necessarily used it for individuals with ulcerative colitis or Crohn's disease or, you know, like any other severe gastrointestinal disorder, because we're concerned about their tolerability over time. Even if we do a lower dose for a longer period of time, but I'll pass it along to the other panelists to see if they've seen it in people with ulcerative colitis per the question. I've used these medications pretty successfully in patients who have inflammatory bowel diseases across the spectrum. I like to ensure that their symptoms are stable, that they're on a stable regimen. And ideally they're in kind of remission, if you will, from their inflammatory bowel disease before kind of considering something like this. Making sure that we educate people adequately with regards to potential adverse effects, symptoms, get ahead of things that are possible complications, including constipation, to make sure we're not aggravating symptoms along the way, I think is a really important thing. Whether or not to empirically start with the intent of doing a slower dose titration, it's up to provider discretion, just making sure that we give patients a clear avenue to get in touch with us if they're having any change in their bowel symptoms that they're concerned about for us to reconsider things. I think there's so many things that we don't fully understand about these therapies that can help a spectrum of my patients who are living with autoimmune and other complications with regards to inflammation and immune function that I'll say that there appears to be a beneficial effect. But of course, we don't really have data with that where there's improvement in quality of life and just energy levels and other things which may be related directly to the weight reduction improvements and other health things. Or there may be other direct effects of the medication on underlying disease states. These things we don't fully understand, but I think it's a great opportunity for shared decision making with our patients. I'd just like to add to Dr. Almodoz's comments that we've been looking at this with some of our local gastroenterologists and with semaglutide in particular, because there has been some evidence demonstrating the anti-inflammatory properties with semaglutide and whether that is a class effect or not, it's too soon to say. But we've used it successfully in patients with stable inflammatory bowel disease across all types of spectrums, and as long as it's not impacting gastric motility too badly. So it's really only in patients with significant gastroparesis, whether that's related to diabetes or other causes, that that would sort of be a hard stop for me. But in UC and other variants of IBD, we've used it successfully. And again, that's anecdotal evidence. So definitely we need to individualize the treatment and choose correctly our patients that are going to be treated with this type of medication. All right. So do we have any other questions? Okay. There's another question here. I have a patient with type 2 diabetes with history of pancreatitis a couple of years ago. His triglycerides are in the 300s now. He's non-compliant with diabetes meds and has diabetes complication. He's motivated to use GLP-1 receptor agonists and will benefit from GLP-1 in weight loss. Would you consider prescribing GLP-1 for this patient? I mean, I think I can make this quick, and maybe the others agree. Yeah, I've used GLP-1s in this individual. I mean, I think that's why we always assess, like, if I encounter someone with a history of pancreatitis and I see that in the chart before I meet them, I make sure that I kind of go over what happened, when did it happen, et cetera, because there's other contributing factors that could be resolved now. And if it's been years, as this question is asking, then I would feel comfortable. It goes back to what we talked about with the education and making them aware, but also when to report, and I think then making sure that we follow up regularly with them, even if it's a telephone, right, if they can't come in, at least calling them to make sure that they're okay and assessing their tolerability. But, yeah, I would feel comfortable with this. Yeah, absolutely. I think, you know, if we attribute the kind of inciting thing for the pancreatitis to the triglycerides, and we know that we're going to have an improvement in the glycemia that's likely fueling the high triglyceride levels, and that there can be improvements in how we store or dispose of intravascular lipid with a combination of weight reduction and improvements in, let's say, metabolic health as part of an incretin-based therapy journey, I think it's appropriate to treat in this situation. But, of course, again, counseling the patient with regards to particular symptoms for which they should report and having a low threshold for stopping.

obesity treatment

stigma

pharmacotherapy

GLP-1 receptor agonists

patient-centered care

side effects

medication adherence

accessibility issues

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nutrition