DNPAO Seminar Series – October 24, 2024 Advance in Evidence-based Obesity Treatment: New Anti-Obesity Medications as Companions to Behavior and Lifestyle Programs 00:00:03:00 - 00:00:29:04 Unknown All right. Let's go ahead and get started. Thank you so much for joining us for the DNPAO Seminar Series and for this important seminar we're having today on obesity treatment, anti-obesity medications, and companion behavior and lifestyle programs. We're so glad to have you join us. I'm Janelle Gunn, and I serve as the Associate Director for Policy, Partnerships and Communications in CDC's Division of Nutrition, Physical Activity and Obesity. 00:00:29:06 - 00:00:34:24 Unknown These seminar series are seminars we do throughout the year. So these will be posted later on our website. 00:00:34:24 - 00:00:48:12 Unknown Just a few housekeeping things. This has been going to be recorded. All lines are muted. We encourage you, if you have questions throughout the seminar, to put it in the Q and A box, and we will address as many of those as we can. 00:00:48:14 - 00:00:52:03 Unknown during this time we have allotted for the seminar today. 00:00:52:03 - 00:01:14:02 Unknown So so pleased with such a great turnout today. It's great to really see the public health interest as we continue to address obesity. CDC recently released new obesity data. The first you see here is the state-level data from the Behavioral Risk Factor Surveillance System that we released last month, showing that 23 states had an adult obesity rate at or above 35%. 00:01:14:02 - 00:01:33:21 Unknown Also last month, CDC released some national-level data from our National Health and Nutrition Examination Survey showing about 4 in 10 adults had obesity. Now recall the BRFSS survey, or Behavioral Risk Factor Surveillance System , is self-reported and NHANES is measured height and weight. 00:01:33:21 - 00:01:42:22 Unknown And just last week, CDC released a Quickstat showing some of the child data, also from the National Health and Nutrition Examination Survey. 00:01:42:24 - 00:01:48:24 Unknown So lots of new data for us to have as we think about what the public health solutions and opportunities are. 00:01:48:24 - 00:02:01:23 Unknown I also want to note that this year we've really done a lot of work in expanding our Family Healthy Weight Programs. This was a commitment in the White House National Strategy on Hunger, Nutrition and Health to expand these evidence-based programs. 00:02:01:23 - 00:02:12:02 Unknown So CDC is currently working on this through three of our funding announcements. And you can see here on the map where we’re locate, where these programs are located in United States. 00:02:12:02 - 00:02:20:14 Unknown I'm super excited today for this amazing panel that we have, to talk about, talk about the topic area. So first we have Doctor Aly Goodman. 00:02:20:15 - 00:02:46:04 Unknown She's a pediatrician and medical epidemiologist with me here at CDC in the Division of Nutrition, Physical Activity and Obesity. She's also a Captain in the US Public Health Service. Doctor Goodman's role as the Obesity Prevention and Control Branch Chief’s Population Health and Health Care Unit Lead, includes improving access and uptake to evidence-based interventions for obesity prevention and treatment, and a robust health services research portfolio. 00:02:46:06 - 00:03:09:21 Unknown Also glad to have Doctor Sarah Armstrong join us. She's a Professor of Pediatrics and Population Health Sciences and Division Chief of General Pediatrics and Adolescent Health at Duke University. She is the past Chair of the American Academy of Pediatrics Section on Obesity, and is a coauthor of the 2023 Obesity Clinical Practice Guidelines. Her clinical work is caring for children and adolescents with obesity. 00:03:09:23 - 00:03:36:20 Unknown And her research focuses on clinic-to-community collaborations to improve child health and well-being. Also so glad to be joined today by Doctor Ariana Chao. She's an Associate Professor in Johns Hopkins, John Hopkins School of Nursing and sorry, the School of Nursing and in the School of Medicine. She's the Director of Research at the Health at Healthful Eating Activity in Weight programs at the Johns Hopkins School of Medicine. 00:03:37:01 - 00:04:03:09 Unknown Her program of research is focused on the development and evaluation of innovative interventions for obesity and related eating behaviors that improve physical and mental health. Doctor Chao has over a decade of experience as a family nurse practitioner. And her work has been supported by the National Institutes of Health as well as the foundation and industry sponsors. Doctor Chao received her Bachelors of Science in Nursing and a Masters of Science in Nursing, 00:04:03:12 - 00:04:13:21 Unknown Family Nurse Practitioner from Boston College and a PhD from Yale. So as you can see, we have an outstanding panel today for our seminar. 00:04:13:21 - 00:04:29:03 Unknown We'll be reviewing new, highly-effective medications to treat diabetes, obesity, and cardiovascular disease. Treating obesity in youth and the importance of lifestyle modification. And we will wrap this up with a Q&A. 00:04:29:05 - 00:04:35:01 Unknown So without much further ado, I'm going to hand the mic over to my colleague, Doctor Aly Goodman. 00:04:35:18 - 00:04:42:21 Unknown Thank you so much. Janelle, and thank you for having me today. It's an honor to be able to present. 00:04:43:17 - 00:04:55:05 Unknown So I'll be speaking today about advances in evidence-based obesity treatment and new, anti-obesity medications that are companions to health behavior and lifestyle treatment programs. 00:04:55:17 - 00:05:40:08 Unknown So what influences body weight and body composition? We talk a lot about what we see above the iceberg here in this slide. The environment and genetics. But it's so much more complicated than that. Stress poor sleep, sedentary lifestyle, unhealthy food can all impact our weight. But, medications also taken for various conditions can also contribute to weight gain or loss and other, you know, really important factors such as excessive screen time, pregnancy, the gut microbiota, life events, endocrine disruptors, disruptors, environmental chemicals, all of these things impact our body weight. 00:05:40:10 - 00:05:56:17 Unknown So all of these factors are interacting all of the time. Right? And it making it really challenging for all of us in the obesogenic environment that we all live in to maintain or even reduce body weight over time, if that's what's needed. 00:05:56:24 - 00:06:34:09 Unknown Obesity is a remarkably complex, chronic and relapsing remitting metabolic disease of energy balance. It is driven by a very complicated and dysregulated interactions of hormones and the brain. It’s what I'm going to talk about today. Obesity was declared a disease over a decade ago by the American Medical Association. Systematic new concept to call it a disease but we have we are understanding more and more about the pathophysiology, what's happening in the body, so that we can really understand what's going on. 00:06:34:09 - 00:06:54:05 Unknown So I want to acknowledge first the complexity of the diagrams on this slide. But I'm going to walk you through it in a way that I hope is helpful. So the first point here is that adipose cells, adipose cells it's just another name for a fat cell, they store fat, but they're very, very metabolically active. 00:06:54:07 - 00:07:27:23 Unknown They're not just passive cells, which is what was used to be thought. And these, they have various levels of activity that are based on their location. So whether they're visceral, meaning around an organ, or subcutaneous, meaning under the skin. And it's really important to understand that based on where they are, that kind of dictates their function. And also, the relative risk of how, of, how those might affect health. 00:07:28:00 - 00:07:59:12 Unknown So when adipose cells become larger, they can become inflamed. And then they release what we call pro-inflammatory cytokines. Cytokines are chemicals used in the body to transmit signals. So this inflammation can then spread throughout the body. And it triggers more inflammation from other cells lots of other different types of cells. And one example is a macrophage, which is the sort of scary looking, purple-ish cell up at the top left of that diagram 00:07:59:14 - 00:08:28:20 Unknown in the first illustration. And then that just triggers more and more chemical signals throughout the body, and in lots of different organs that are becoming angrier and angrier and more and more inflamed. The other thing that these enlarged adipose cells do is release lipids. Lipids are a, another name for, a type of fat within the body that can deposit in various tissues, such as the liver, in blood vessels, and in the heart. 00:08:28:22 - 00:08:48:19 Unknown And these cumulative effects of inflammation and lipid deposition, or deposits, can lead to significant changes in multiple tissues and multiple organ systems over time. And it's those changes that pose significant health problems. 00:08:48:19 - 00:09:18:14 Unknown Again it's that inflammation and the lipid deposits that we're really concerned about. It's so one example of that is what's called vascular endothelium dysfunction. Say that fast ten times a day. But what it means is dysfunction of the lining of the blood vessels, which can result in hypertension or high blood pressure. Inflammation is also known to contribute to chronic kidney disease and to the development and progression of cancer. 00:09:18:16 - 00:09:33:04 Unknown It also contributes to cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, and diabetes. All of these health issues are linked to inflammation and lipid deposits that are caused by obesity. 00:09:33:04 - 00:09:51:16 Unknown So here is another really complicated figure. But it's here to demonstrate the very, very complex pathways that regulate body weight and metabolism. But these complex systems have also led to opportunities for pharmacologic interventions. 00:09:51:18 - 00:10:18:13 Unknown So put it in a straightforward way. Food consumption when we eat stretches the stomach and the small intestine, and that triggers the release of hormones that signal many organs around the body that are involved in metabolism. Two of the main hormones that are involved in these pathways that we're going to focus on today are called GLP-1, or glucagon-like peptide one, and GIP. 00:10:18:15 - 00:10:38:15 Unknown Glucose-dependent insulinatropic peptide polypeptide which are shown in the middle in green. So just highlighting for you how complicated this is and how there's all these hormones and all these signals kind of running around to all these organs to regulate. But those are the big ones we're going to talk about, GLP-1 and GIP. 00:10:39:09 - 00:11:04:15 Unknown So these multi-use drugs that influence those hormones of GLP-1 and GIP are really substantial advancements in the treatment options for obesity, diabetes, and cardiovascular disease and likely many more other conditions that we're going to find out about over time. And these drugs offer exciting possibilities for addressing multiple chronic health conditions. 00:11:04:15 - 00:11:11:20 Unknown So these medications work by targeting the hormones that are involved in regulating metabolism. 00:11:11:22 - 00:11:43:13 Unknown And they can affect various organs that are involved in, you know, different aspects of of those circuits. A GLP-1 receptor agonist is one type of medication that increases the effect of the GLP-1 hormone that I showed you before. And agonist is a chemical that activates a receptor to produce a biological response. So basically an agonist increases the effect of a hormone. 00:11:43:15 - 00:12:13:23 Unknown That's how this medication works. So for example a GLP-1 receptor agonist medication can increase insulin output from the pancreas. It can affect brain pathways that decrease appetite or increase feelings of satiety, or fullness. They reduce inflammation and insulin resistance in the liver, and in muscles. Increase endothelial function and blood vessels and have impacts on the kidneys and in the heart. 00:12:14:00 - 00:12:23:03 Unknown So by impacting these hormones and signaling pathways in many organs, these drugs can have positive effects on various chronic diseases. 00:12:24:09 - 00:12:49:08 Unknown These medications are new. And the terminology around using them is still evolving. So you'll hear me use some terms. You might hear the other presenters use different terms. And in the media the terms are all over the place. And that's because this is just like such a new field. So one term being used is what's called nutrient stimulated-based hormone therapies. 00:12:49:11 - 00:13:17:17 Unknown Again, complicated words or NuSHs. You’ll also hear incretin-based therapies. And that's sort of an overall class based on the pharmacologic agents. But in the obesity field, these drugs are often referred to as part of a broader category of anti-obesity medications or AOMs. Notably, AOMs that's not a term that CDC invented. That's a term that's used across the, you know, across the field. 00:13:17:19 - 00:13:41:09 Unknown But it AOMs include lots of medications, not just GLP-1 based medications. So it could be phentermine topiramate or Orlistat. Lots of different medications to treat obesity and GLP-1s. But different terms might be used in other fields. So for diabetes they might be called GLP-1 receptor agonist for diabetes treatment but for cardiovascular disease prevention. 00:13:41:09 - 00:13:55:18 Unknown They might be referred to as GLP receptor agonist to prevent major adverse cardiovascular events. So the important point here is just that these are medications known by many names right now, depending on the context and the field of study. 00:13:55:18 - 00:14:08:03 Unknown So again these medications are highly effective because they target the underlying imbalances that contribute to persistent obesity. 00:14:08:05 - 00:14:32:12 Unknown They achieve this by slowing down digestion, stimulating insulin release, preventing glucose from entering the bloodstream, and influencing brain processing to increase feelings of satiety. And the combined effects of all of these actions often lead to weight loss and therefore improved metabolic health. 00:14:32:12 - 00:14:43:14 Unknown This slide gives a big picture view of how percentage weight loss is related to health related outcomes, which is really crucial for addressing chronic diseases. 00:14:43:16 - 00:15:17:22 Unknown Up at the top, you'll see the bar that shows increasing percent weight loss. In pink horizontal bars, you see cardiometabolic outcomes. And in blue horizontal bars, biomechanical outcomes. So intensive lifestyle interventions such as the Diabetes Prevention Program for Adults or Family Healthy Weight programs, which are for children and their caregivers on average, often lead to a median like 5% weight loss, sometimes up to 10% reduction in weight at 6 to 12 months. 00:15:17:24 - 00:15:54:00 Unknown And that is really important and really amazing. But you can see here that a 5 to 10% weight reduction is usually associated with type two diabetes prevention, improvements in physical function, reduced type two diabetes hyperglycemia, reduced hypertension, which are all really important, right? However, if you need other improvements in chronic disease outcomes like type two diabetes remission or cardiovascular disease risk reduction, larger reductions in percent weight loss are necessary. 00:15:54:02 - 00:16:30:18 Unknown And so you'll see those outcomes if you look further to the right on this chart, the gray, vertical shaded area here reflects the percentage of weight reductions seen on average in clinical trials for adults that are taking a GLP-1 receptor agonist called semaglutide, I'm going to talk about it in a moment. So you can imagine that for individuals who need a 10 to 20% weight reduction to get to their desired outcome in terms of chronic disease treatment, these medications can be a highly effective tool 00:16:30:20 - 00:16:32:20 Unknown in addition to lifestyle treatment. 00:16:33:22 - 00:17:08:12 Unknown These drugs are not brand new. In 2017, GLP-1 agonists were first approved for diabetes treatment. In 2021, they were approved for adult obesity, thats with a BMI of 30 or greater, or for individuals with overweight and one weight related health outcome, excuse me, health condition. In 2022, they were approved for children ages 12 and above, with obesity, defined as BMI greater than the 95th percentile or higher. 00:17:08:14 - 00:17:43:03 Unknown And in 2023, approved for cardiovascular disease treatment. But now let's focus on the medications themselves. There are two GLP-1 based compounds that are currently FDA approved in various formulations. And those are called semaglutide and tirzepatide. For diabetes, one commonly known medication is Ozempic, you commonly hear about, that is semaglutide. That's a compound at a lower dose of one milligram per week. 00:17:43:05 - 00:18:06:19 Unknown Tirzepatide, the other compound I told you about, which is a combination of a GLP-1 agonist and a GIP agonist when used for diabetes, is known as Mounjaro. And again, you probably have seen commercials for these on TV, or you might have friends or family members, or you might be taking them yourself. For obesity, the GLP-1 based medications are higher. 00:18:06:21 - 00:18:36:21 Unknown Semaglutide is dosed at 2.4mg per dose per week, and tirzepatide at 10 to 15mg. When semaglutide is used for obesity, it's called Wegovy, and tirzepatide is called Zepbound. For cardiovascular disease., semaglutide is also the approved drug, and it's also marketed as Wegovy, and it's approved to reduce the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease. 00:18:39:05 - 00:19:11:03 Unknown The National Clinical Guidelines for Diabetes and Obesity include GLP-1 and GIP receptor agonists as part of the treatment options for adolescents and for adults. That's really important to know and to remember that intensive health behavior and lifestyle interventions that include nutrition and physical activity counseling, along with behavior modification, are considered the foundational treatment for obesity and diabetes. 00:19:11:05 - 00:19:29:22 Unknown These interventions address various aspects of healthy living, especially because we all are living in an obesogenic environment and that includes stress management, sleep, coping, and lots of other factors that we saw way back on the glacier slide at the beginning. 00:19:29:22 - 00:19:42:23 Unknown It's also important to note that intensive lifestyle interventions are essential for obesity treatment, regardless of whether an individual is taking a medication. 00:19:43:00 - 00:20:10:13 Unknown Many people might not want to take a medication or might not be able to access one, or it might not be indicated, or they could have a contraindication. But lifestyle intervention is always an option and always a strong option for them. Also, it's incredibly important to understand that the FDA approvals for these medications specify that these medications must be used as an adjunct to lifestyle treatment. 00:20:10:15 - 00:20:39:04 Unknown Lifestyle interventions have been shown to lead to improved quality of life, improve relationships with food, self-esteem, body composition, and overall health. And these are outcomes that are not necessarily addressed with the medication alone. However, we recognize that in real world practice, the use of these medications along lifestyle interventions is not always occurring as was originally intended based on lots of various issues in the field 00:20:39:04 - 00:20:40:23 Unknown right now. 00:20:40:23 - 00:21:09:21 Unknown These medications are available only by prescription and have specific health criteria for their use. They are administered through self injection with prepackaged doses that may be increased over time based on the desired health effects and side effect profiles. Again, it is important to note that these medications should be used in combination with lifestyle therapy. The most common side effects include nausea, diarrhea, constipation, and abdominal pain, and those can be substantial. 00:21:09:23 - 00:21:40:12 Unknown Up to 30% of individuals may experience side effects, particularly during the first month of usage and when dosages increase. While some people find the side effects intolerable and discontinue treatment, for many others, the side effects may subside within 1 to 2 months, and allow them to continue with the medication. Clinical trials have shown that many people experience weight regain when the medications are stopped, and on average, weight regain is around 70 to 80% of the lost weight. 00:21:40:14 - 00:22:11:15 Unknown Combining lifestyle treatment with these meds has been shown to help mitigate the extent of weight regain after discontinuation. Again, another really important reason that we want to pair lifestyle treatment with the use of medications. However, access and availability of the meds can be challenging due to insurance coverage issues and many others. Out-of-pocket costs without insurance coverage can range from $1000 to $1600 per month. 00:22:11:15 - 00:22:33:09 Unknown As exciting of a time as this is for the field, there are emerging concerns and many research opportunities. There is a major need to understand better understand how to pair these medications with lifestyle interventions. How much dose of lifestyle intervention is needed? How do we need to modify the content of lifestyle interventions? Where can we deliver that? When? And for how long? 00:22:33:11 - 00:23:03:16 Unknown There are increasing reports about adverse events in real world settings, including overdoses by adults or by children of adults who are prescribed the drug. Injection injuries due to people breaking apart the injection devices to make the drug, the drug last longer. Lots of reported adverse events that we need to be closely monitoring. Rapid weight loss, particularly with certain medications, has raised concerned about the loss of lean muscle mass, leading to issues of frailty and sarcopenia, which mean for loss of muscle tissue 00:23:03:16 - 00:23:32:21 Unknown as part of the aging process. Lack of access to physical activity and appropriate counseling can can, you know, contribute to these concerns. We also have concerns about potential micronutrient deficiency due to restrictive eating patterns. Long term use of these medications is an area where much more research is needed to understand the effects over extended periods. Tapering protocols, such as gradually reducing the dosage over time, also require further investigations. 00:23:33:06 - 00:24:07:19 Unknown In today's presentation I've discussed GLP-1 and GIP agonist agonists. But there's also many other hormones being targeted for drug development. In terms of research, there's over 70 new drugs currently in clinical trials. Over 70. We are at the dawn of a new age in the development of medications for these complex metabolic and chronic diseases. So the important takeaway of this complex slide is just to know that there's many, many new drugs coming down the pipeline to market over the next decade. 00:24:07:19 - 00:24:34:08 Unknown There are currently substantial inequities in access to GLP-1 based medications that are based on issues, and access, availability, and cost. We know that access is more readily available for individuals with diabetes compared to those with obesity. That has to do with Medicare as well as other insurers not considering obesity as an indication for coverage of these medications. 00:24:34:10 - 00:24:48:23 Unknown But it also has to do with availability, as drug manufacturers struggle to meet the demand. Cost is another very significant barrier with the prices of these medications making them financially prohibitive for many individuals. 00:24:48:23 - 00:25:05:05 Unknown We'd be remiss not to, acknowledge strongly the role that weight stigma and bias have to play. Public health has a crucial role in addressing weight stigma and bias, and promoting effective prevention and treatment strategies. 00:25:05:07 - 00:25:43:23 Unknown Weight stigma and bias are pervasive issues, that occur in various settings including social media, health care, schools, where we work, where we play among families, and in policy systems. The individual and public health consequences of weight stigma and bias include mental health issues, reduced physical activity, disordered eating behaviors, self-harm, suicidality, social isolation, and worsening obesity. It is essential for us all to be mindful of these issues when we are considering the use of these medications, and to actively work towards reducing weight stigma and bias. 00:25:47:19 - 00:26:28:18 Unknown Moving forward, our public health opportunities lie in promoting healthy lifestyles for all individuals through quality nutrition and physical activity and behavioral opportunities that support health. And in ensuring that in doing so, we are, reducing weight stigma and bias at every opportunity. These programs should be accessible to everyone, not just those who are using medications, but ensuring that they are available to those using medications. And public health can facilitate equitable access to all evidence-based obesity treatment, including lifestyle programs, medications, and surgery 00:26:28:18 - 00:26:32:10 Unknown when appropriate. Thank you. 00:26:32:17 - 00:26:36:04 Unknown And I'm now going to hand it over to Doctor Armstrong. 00:26:36:14 - 00:26:39:00 Unknown Thank you so much, Doctor Goodman, I appreciate it. 00:26:39:02 - 00:26:47:21 Unknown So we're going to dive right from the basic biomedical sciences right into the clinical application of use of these medicines, with a focus on you. 00:26:47:21 - 00:26:59:22 Unknown So we know there are many challenges with prescribing these medications. But this is clinician is what we are swimming in. Big banner ads that this is the breakthrough of the year. 00:26:59:24 - 00:27:17:17 Unknown The agonist GLP-1 agonist script increased 600% since 2020 for for teens and young adults. We don't see numbers like that often. But we've got these teens and their families really debating is this right for me? So this is a tough situation for clinicians, but we're going to walk through a few key issues. 00:27:18:05 - 00:27:34:22 Unknown So I just want to take note that we really are building this plane while we're flying it. As Doctor Goodman mentioned, there are many research questions that are still unanswered. But I think we have to do the best that we can with the information available, and hopefully I can provide some clinical tips as we go forward. 00:27:35:04 - 00:27:43:07 Unknown So I'd like to start with the focus on the AAP Clinical Practice Guideline Treatment Algorithm from the 2023 Clinical Practice guideline. 00:27:43:07 - 00:27:55:01 Unknown We can see that the area we’ll be focusing on is this category of children with obesity age 12 and older. Now, what the guideline says is that we don't want any watchful waiting anymore. 00:27:55:03 - 00:28:15:15 Unknown Now, does that mean that every 12 year old has to go on medicine, and every 13 year old has to go on surgery? Of course not. What that means is that we have to be able to educate and provide opportunities, guidance and information on all of these options and work with patients and families using shared decision making to make the best possible choice. 00:28:15:15 - 00:28:16:09 Unknown 00:28:16:17 - 00:28:38:18 Unknown Many people ask, is it okay if I just start with intensive health behavior and lifestyle treatment, or IHBLT? And the answer is absolutely yes. So I really like looking at this data slide. This is the semaglutide trial for adolescents. And while on the left you can see yes, the kids did really well in the semaglutide group. It's a very good medication. 00:28:38:20 - 00:29:00:17 Unknown You can see on the right side and the placebo group, there's a lot of kids that did pretty good with that placebo, which included lifestyle intervention. So while we don't know upfront who is going to respond well to lifestyle and who might need medication, we do know that there's a good chunk of kids that are going to respond really well to lifestyle treatment, so it is absolutely okay to start with that. 00:29:00:17 - 00:29:25:12 Unknown Now when we're thinking about who might need medication in addition to lifestyle treatment, here are a few clinical pearls I’ve learned since starting to prescribe these. Children with more severe obesity might benefit from these medications, as an aid to getting them in a more healthy range. And those who have existing comorbidities that might need more urgent resolution. 00:29:25:14 - 00:29:49:02 Unknown Sometimes there's patients that are really distressed by this experience of hunger and what they call food noise in the background. That's kind of a what's in the pantry, what's in the fridge, always thinking about food, very distracted feeling that these medications really do help with. Adolescent preference is always really important in supporting their autonomy and how they would like to manage their own obesity. 00:29:49:04 - 00:30:25:05 Unknown Many times family history plays into this. Either there's a family history of severe obesity, or there are people who have taken medications in the family and have either a positive or negative experience with that. That often weighs into the decision as well. I have found that youth with physical or psychosocial limitations caused by their obesity, or that they have otherwise, for example, youth who might have cerebral palsy or muscular dystrophy or who may have a psychosocial impairment due to bullying or teasing, internalization of that weight bias that doctor Goodman mentioned earlier. 00:30:25:07 - 00:30:47:07 Unknown They might be people who might benefit from these medications. And then in the intellectual developmental disability category, I have a number of patients with autism who, based on the inability to do physical activity or limitations to that, food sensitivities, preferences, really are helped by these medications. So these are just some clinical thoughts about who you might consider. 00:30:47:07 - 00:31:12:13 Unknown So the second tip is really providing good education. And I think this is so important not just about the medicine, how it works, side effects, but also setting those expectations. I saw a couple questions in the chat about you know what if it's not covered, where can patients find it? I think it's really important that providers and nursing staff are trained in how to show patients how to use these medications, particularly in pediatrics, where we really don't do injectables. 00:31:12:14 - 00:31:34:00 Unknown This is new. This is going to sound different from things we've done before. I find it helpful to have a supply of demo pens and the ramp up chart you see here. This one is for semaglutide, but you can have it for phentermine topiramate or liraglutide for any of the FDA approved medication. Having these things available in the office as teaching tool really, really helps. 00:31:34:02 - 00:32:05:03 Unknown Showing them where the injection site is, either the abdomen, back of the arm, thigh, those are good places and letting them show you that they heard you. So doing teach back. I do try to educate families about the need for prior authorization for most of these, if it's covered at all. And potential drug shortages, particularly at those lower beginning doses, sometimes it can be really hard to find, and they need to just be patient and not keep switching the medicine to different pharmacies because they end up at the bottom of the list at the new pharmacy. 00:32:05:05 - 00:32:27:14 Unknown I like to have families really understand that we need to do monthly visits to doseage-up, because sometimes we might hold it a certain dose for a couple months if they're experiencing some nausea or vomiting before we advance further. And then I like to follow every three months afterwards to monitor. I do warn people that there are a small fraction of people who don't respond to these medicines. 00:32:27:14 - 00:32:46:02 Unknown We're not entirely sure why, but if they have less than 5% BMI reduction at about three months, then maybe they're one of the non-responders. But we can always try something different. I want to make sure they understand what long term treatment means when we say that. If you're 14 and starting on a medicine, that is for the rest of your life, that's a long time. 00:32:46:04 - 00:33:12:08 Unknown So I want to make sure they understand that if they stop the medicine, what we know so far, that weight regain is expected. Maybe we can wean. Maybe we can reduce the dose. We don't know the answers to those yet. I just want to make sure families really understand that. And then I always document that there are no contraindications, in particular, the risk for follicular or medullary thyroid cancer, in the chart because that often is looked at for insurance coverage. 00:33:12:08 - 00:33:34:23 Unknown I really do, also, my third tip is emphasizing the importance of strength training. And Doctor Goodman mentioned this. But whenever you have weight loss there's lots of total body fat but also lost the lean muscle mass. And that's not good for growing teenagers. In fact, a year of incretin therapy or GLP-1 therapy, is associated with almost a decade of aging in terms of the muscle mass loss. 00:33:35:00 - 00:33:54:22 Unknown The other potential thing at the bottom part of this figure is we don't know this yet, but maybe if there's strength training while the weight loss is happening, maybe we could reduce the dose or come off and not have such a great weight rebound. So I think that's really helpful. Now if patients can access IHBLT, great, they can get that physical activity incorporated. 00:33:54:24 - 00:34:20:11 Unknown If not, for teenagers I recommend either at home strength training using either body weight or just what's around the house or local opportunities. The YMCA, parks and recreation, often have sliding scale fees. Planet fitness does an awesome free for teens every summer opportunity, so that's great. Or they can sign up for their school electives. Many schools now have weight training electives in the school, so these are things to look for. 00:34:20:11 - 00:34:41:09 Unknown My fourth tip is really about nutrition and how to feed a teenager on obesity medication. So again most IHBLT is going to address these general nutrition concepts but if you don't have IHBLT around, there's a few things to think about. So appetite reduction is good for weight loss and it can be bad sometimes. 00:34:41:09 - 00:34:59:17 Unknown So a lot of these kids have been trying their whole lives not to eat too much. Now their appetites taken away. And so I have some patients who are tempted to just not eat, which obviously is not healthy. So I do try to make sure we're following very closely to ensure they're eating regular meals, even if they're small throughout the day. 00:34:59:19 - 00:35:20:03 Unknown I encourage them to have protein at every single meal, again to prevent that muscle mass loss. And I recommend they eat it first, because a lot of times these medications cause satiety so quickly that once they eat a few bites of food, they may not want the rest. So I don't want them to fill up on the pasta and not make it to the salmon or chicken or whatever the protein is. 00:35:20:05 - 00:35:37:10 Unknown Sips of water between bites can help avoid the nausea we know is a side effect, particularly with the GLP-1. Avoiding fatty foods around the day of the injection is helpful to avoid nausea. And this is not evidence based, but I, as a pediatrician, just put everybody on a multivitamin knowing if they're going to have rapid weight loss. 00:35:37:10 - 00:35:40:00 Unknown I want to make sure we have those nutrients there. 00:35:40:00 - 00:35:58:15 Unknown My fifth tip is to really address social drivers of health and peer family support systems. Again IHBLT will likely do this, but if you don't have that, I suggest screening all patients you're going to put on a anti-obesity medicine for social drivers, particularly food insecurity, transportation and housing. 00:35:58:17 - 00:36:18:05 Unknown Those are the things that ultimately seem to influence whether or not they can access or continue to take the medicine safely. I think it's important periodically to check in on their quality of life, relationships, self-image. You know, rapid weight loss in teenagers is almost kind of like a little adjustment disorder. And I think it's important to check in and see how they're doing with that. 00:36:18:07 - 00:36:24:19 Unknown And then using all of this community based resources that you have accessible to address anything that comes up positive. 00:36:25:16 - 00:36:47:10 Unknown Okay. My sixth tip I feel very strongly about, I think this is so super important is that we really have to co-manage obesity and mental health and eating disorders. So we know that eating disorders are more common in teens with obesity. So I recommend that we screen at baseline and routinely. There's no perfect eating disorder screen in people with bigger bodies, particularly teenagers. 00:36:47:12 - 00:37:08:01 Unknown But the EDE-Q and SCOFF kind of get at the general concepts that are important. We also know that depression is more common in teens with obesity. So I also recommend screening at baseline. And periodically we use the PHQ-29. There has been some public concern about suicidal ideation with GLP-1., so I'm going to show you some reassuring data in a minute. 00:37:08:03 - 00:37:13:14 Unknown But I think it's never hurts to screen and follow. And I like the ASQ for teenagers as a good screen. 00:37:14:09 - 00:37:34:15 Unknown And some reassuring information, so we do know, and this is just a study that was published just this month in JAMA Pediatrics, the fast track to health randomized trial. So, they found that with different lifestyle treatments, either an intermittent energy restriction or continuous energy restriction, which I don't know that I'd recommend restriction in any way, 00:37:34:15 - 00:37:49:13 Unknown but the point being that this is done in the setting of lifestyle treatment, that we can see that lifestyle treatment in teens reduces symptoms of depression, eating disorders, and subjective size, weight and eating concern. So that is reassuring to see. 00:37:49:13 - 00:38:05:14 Unknown And then maybe most reassuring, this large study that just came out also in JAMA Pediatrics this month, we had a big issue this month, is that GLP-1s do not increase the risk of suicidal ideation or suicidal attempt in adolescents. 00:38:05:14 - 00:38:26:24 Unknown And this is a very large data set. So you can see the effect is actually for suicidal ideation and attempt is actually decreased among those taking a GLP-1. The only thing that was increased in that group was the GI symptoms, which we expect as a known side effect of the medication. This study was not powered to draw the conclusion that GLP-1s prevent suicide in teens. 00:38:26:24 - 00:38:33:20 Unknown I don't want anyone to walk away with that impression, but at least we can say pretty clearly they don't increase the risk, which I think is reassuring. 00:38:33:20 - 00:38:48:07 Unknown And then last, I offer this resource, the Stop Obesity Alliance, to check your local and state coverage plan and supply and shortage issues. This applies to both Medicaid and commercial plans. 00:38:48:09 - 00:38:53:01 Unknown This is changing all the time, so be sure to check and see what's covered in your area. 00:38:53:01 - 00:39:06:06 Unknown And I just want to point you to an article that we can link in the chat also, last year, an NIH workshop that went over all of these barriers and issues that I won't go through again. But it kind of goes through all of them 00:39:06:06 - 00:39:08:15 Unknown and how, what we know about them at this time. 00:39:08:15 - 00:39:29:07 Unknown So in conclusion, our goal is to provide evidence-based care to all of our patients using non-judgmental language and shared decision making so each family can get the most safe, effective, and value-consistent care possible. And now I'd like to pass it off to my colleague, Doctor Ariana Chao. 00:39:29:09 - 00:39:30:08 Unknown Thank you. 00:39:31:16 - 00:39:45:11 Unknown Excellent. Thank you so much, Doctor Armstrong. Good afternoon everyone. I'm really grateful to have the opportunity to speak with you today about this important topic. I'll be covering implications for adult patients in my presentation. 00:39:46:07 - 00:40:00:20 Unknown Here are my funding and disclosures. So I have participated in research studies pertaining to obesity treatment with the groups listed here. And I have also served on advisory boards and consulted with Boehringer Ingelheim, as well as Eli Lilly and Company. 00:40:01:03 - 00:40:39:16 Unknown So we have entered a transformational time in the care of people with obesity. Obesity is associated with over 230 complications, ranging from things like type two diabetes to osteoarthritis and obstructive sleep apnea. Discoveries about the mechanism that we heard about earlier underlying obesity have informed the creation of more effective obesity treatments. These new medications have contributed to a paradigm shift, with greater recognition that obesity is not simply a vanity issue, that willpower can cure, but a complex chronic disease with significant health impacts. 00:40:39:18 - 00:41:01:20 Unknown It's important at the outset to recognize that weight loss alone is not the magic solution to all chronic conditions, and there's heterogeneity in responses. However, we can effectively treat obesity, an important root contributor to many conditions. We can help patients achieve clinically significant weight loss and also prevent and improve many related complications. 00:41:01:20 - 00:41:08:10 Unknown This paradigm shift in obesity treatment has been ushered in by a new generation of medications. 00:41:08:12 - 00:41:42:02 Unknown As you can see from this figure showing the average weight losses in excess of placebo and pound, it's clear that these medications produce larger weight losses on average, compared to previous medications. So at the top of the screen, you can see the first generation anti-obesity medication, which produced more modest weight losses that range from placebo subtracted losses of 6 to 19 pounds, whereas with the second generation anti-obesity medication, semaglutide and tirzepatide, they produced average weight losses that ranged from 28 to 47 pounds on average. 00:41:42:02 - 00:42:14:12 Unknown With these average weight, larger weight losses, scientific studies have begun demonstrating the benefits that these medications extend beyond weight loss. Study have studies have shown improvement and things like cardiometabolic parameters, type two diabetes and prediabetes. Other studies have shown improvements in things like pain in people with knee osteoarthritis, reduced onset of major kidney disease in people with chronic kidney disease, as well as reduced symptoms and physical limitations in people with heart failure. 00:42:14:14 - 00:42:33:02 Unknown We also see things like improvements in quality of life as well as physical functioning. I've highlighted here in gray some other squares where there's ongoing investigations of different conditions that these medications might help with. Things like dementia, substance use disorder, as well as binge eating disorder. 00:42:33:02 - 00:42:37:01 Unknown I wanted to highlight some recent clinical trial data too 00:42:37:01 - 00:43:07:09 Unknown that again underscores the implications that these medications can have for in terms of health. So in a randomized controlled trial that included over 900 adults with overweight or obesity and type two diabetes, almost half of participants randomized tirzepatide achieved normoglycemia at the end of the trial. In terms of prediabetes in another randomized controlled trial, we found that over 80% of participants on semaglutide achieved normoglycemia. 00:43:07:11 - 00:43:47:03 Unknown Another randomized controlled trial in patients with obstructive sleep apnea, or OSA, demonstrated that over 40% of those on tirzepatide achieved OSA remission or switched to mild nonsymptomatic status. Lastly, in a cardiovascular outcomes trial for semaglutide, the select trial, it showed that patients with overweight or obesity and established cardiovascular disease but without type two diabetes, that people randomized to semaglutide had a decreased risk of major adverse cardiovascular events, including things like cardiovascular death, nonfatal heart attack, and stroke compared to placebo. 00:43:47:05 - 00:43:50:20 Unknown These medications can truly be life changing for many. 00:43:50:20 - 00:44:14:08 Unknown So as we're adding more tools to the toolbox across the spectrum of treatment and giving much needed options to patients, it's important to again underscore that lifestyle modification really remains foundational. And the as has been said before, the FDA has included that AOMs are indicated as an adjunct to reduced calorie diet and increased physical activity. 00:44:14:17 - 00:44:52:09 Unknown The premise behind this is that medications can help facilitate adherence to lifestyle modification, and vice versa. In fact, our lifestyle modification strategies might help people to actually adhere to these medications as well. It's also important to recognize that engaging in physical activity and eating a heart-healthy diet, has benefits independent of weight status. We also know that, given the amount of people with obesity, stepped care approaches might be a useful treatment strategy focusing on least aggressive interventions being tried first and then elevating in care as needed. 00:44:52:09 - 00:45:18:14 Unknown I highlighted some weight losses before for these new generation anti-obesity medications. And it's important here to emphasize that in those trials they were paired with lifestyle modification strategies as you can see here. These are two examples from these three large clinical trials that were conducted for semaglutide and tirzepatide. The semaglutide study that I'm highlighting here is called STEP one 00:45:18:14 - 00:45:40:03 Unknown and within adults with overweight or obesity. And there's a parallel trial that was done with tirzepatide. As you can see, if you look at the gray lines among people with placebo, there was benefit for those folks in terms of the lifestyle counseling. So you can see that those individuals lost weight on average. You can see that the weight loss is much greater for those taking the active medications. 00:45:40:05 - 00:45:57:23 Unknown But here I wanted to highlight the frequency of counseling that was delivered in these trials. So you can see that in the STEP one trial, there were seven sessions in the first six months that occurred at every four weeks. And then those sessions continued every four weeks thereafter. And the SURMOUNT one trial, the visits were spaced out a bit more. 00:45:57:23 - 00:46:04:18 Unknown So there were five sessions in the first six months and then it spaced out to every 12 months for the remainder of the trial. 00:46:04:18 - 00:46:21:19 Unknown So this highlights very similar to what we heard from Doctor Armstrong about adolescents, that monthly counseling, either in-person or remote, is really recommended during dose titration until folks are stabilized. And then it can be continued monthly or, perhaps quarterly afterwards. 00:46:21:19 - 00:46:41:01 Unknown And I also wanted to give a highlight too in terms of the content that was provided in each of the trials as well. So you can see here the prescriptions for diet and physical activity and behavioral strategies were similar between the two trials. So it included a 500 calorie deficit compared to total energy expenditure. 00:46:41:03 - 00:47:10:16 Unknown And for SURMOUNT one, they also included a macronutrient composition prescription of 30% fat 20% protein, which would be equivalent to about 60g for someone having a 1200 calorie per day diet, as well as a 50% carbohydrate. For physical activity goals, it was 150 minutes per week. And for behavioral strategies, the counseling sessions were done by a dietician or similar qualified health care professional. And individuals also recorded their food intake. 00:47:11:12 - 00:47:40:03 Unknown So with these new generation anti-obesity medications, I just wanted to highlight what is typically done with behavioral obesity treatment alone or with the first generation AOMs, which is intensive lifestyle intervention or ILI. The intensive really refers to the frequency of counseling. So it typically is, even more frequent than we saw in the SURMOUNT and STEP trials of 14 visits in the first six months, with continued monthly visits for maintenance thereafter. 00:47:40:05 - 00:47:52:23 Unknown And this frequency of counseling is necessary to help patients to be able to make dietary, physical activity, and behavior therapy changes in order to produce an energy deficit that allows for weight loss. 00:47:52:23 - 00:48:06:13 Unknown But with the second generation anti-obesity medications, which are more potent or able to produce stronger energy deficit by themselves, we see that lifestyle intervention will continue to be very important. 00:48:06:15 - 00:48:32:06 Unknown But we are shifting strategies in a way to emphasize different aspects that can really help people to optimize their health outcomes. And here I've also added medication adherence, which I think is a really important component of the counseling that we'll be doing. And Doctor Armstrong mentioned that fields are rapidly changing, and we're urgently in need of trials and evidence that examined the optimal lifestyle interventions with the second generation anti-obesity medications. 00:48:32:08 - 00:48:42:16 Unknown And I'm going to go over some recommendations that I use clinically, that have largely been adapted from other weight loss strategies like bariatric surgery or other chronic health conditions. 00:48:42:16 - 00:49:08:21 Unknown So with any medication, there are risks and benefits. And it's critical that we carefully monitor and assess the benefits and risk of the medications. While the second generation anti-obesity medications have consistently demonstrated improvements in things like self-report physical function, we do see a loss of fat-free mass. And loss of fat-free mass occurs with any type of weight loss. 00:49:08:23 - 00:49:33:03 Unknown So you can see here for intensive lifestyle intervention, the amount tends to be 15 to 25% of total weight loss being fat-free mass. And for Roux-en-Y gastric bypass, it tends to be about 30%. You can see in this graph that has semaglutide and tirzepatide, that the amount of fat-free mass, highlighted in blue, range from 25% to 39%. 00:49:33:05 - 00:49:52:00 Unknown So highlighting potential challenges with this. And while there are medications such as bimagrumab, that are being tested to help preserve muscle mass. It's critical that we really encourage different lifestyle interventions that can also help a role in attenuating loss of fat-free mass. 00:49:52:00 - 00:50:10:21 Unknown So here are some recommendations and dietary considerations with these medications, including again highlighting an energy deficit about 500 calories per day, as well as making sure individuals are getting adequate amounts of protein, very similar to what we heard for the teens. 00:50:10:23 - 00:50:40:19 Unknown And typically this is recommended spread across meals, Fluid intake, you can see here as well as fiber amount to make sure people are staying well-hydrated as well as taking care of their gut health. Many individuals with obesity actually have preexisting micronutrient deficiencies. So it's really important to counsel on adequate intake and considering supplementation as well as encouraging a diet that has lean proteins, fruits, vegetables, and fewer highly processed foods. 00:50:40:21 - 00:50:52:09 Unknown Periodically monitoring food intake can also be really helpful to make sure individuals are meeting these goals and evaluating relationships of things like GI side effects with dietary intake and timing of intake. 00:50:52:09 - 00:51:13:16 Unknown For physical activity, it's really important to emphasize things like walking for the cardiovascular benefits. Typically recommendations about 150 minutes per week during weight loss and increasing to 250 minutes per week when people have weight loss maintenance and again emphasizing resistance training to really help attenuate loss of lean muscle mass. 00:51:14:07 - 00:51:50:17 Unknown And while these medications are powerful tools, we are far from medications that would universally be able to replicate the full benefits of exercise and a healthy diet. So the medications alone cannot completely address things like having enough time to exercise, or grocery shop and cook; how to implement getting that 60g of protein per day. So these are really areas where our lifestyle counseling is really necessary, as well as, making sure that there's a conducive food and physical activity environment for patients to be able to have enhanced health benefits. 00:51:50:17 - 00:52:14:02 Unknown We also know that when we have more barriers, that we have less adherence to the medication. So really being able to holistically address things like socioeconomic factors, addressing availability, access, healthcare system factors, patient-related factors, as well as thinking about therapy-related factors are critical to really enhancing the effectiveness of these medications in real world setting. 00:52:14:02 - 00:52:33:21 Unknown Lastly, I just wanted to highlight that lifestyle modification will remain the foundation of any sort of obesity treatment. And as we focus, not only on quantity but quality of weight loss, it will really be important to be emphasizing and maximizing different lifestyle modification programs that can help patients achieve their best outcomes. 00:52:33:21 - 00:52:55:08 Unknown And I want to thank you all so much for your attention. And I will turn it back over to you, Janelle. Okay. Thank you. Thank you so much to our panelists. We invite you to come back on camera. What a great seminar. Really great information. The state of where things are, its implications for the youth, and implications for adults. 00:52:55:10 - 00:53:17:10 Unknown We were able to answer several of the Q and A's in the Q&A box, if you want to take a look there. Maybe if I can sneak one in before we close out. Aly, we have a question on how like these lifestyle programs or family healthy weight programs may be contributing to disordered eating. And I'm wondering if you could address that. 00:53:17:18 - 00:53:57:08 Unknown Sure. And I think Doctor Armstrong can as well. It's a great question and a really important consideration. Thankfully, what's been seen in a number of research studies, and certainly what we've experienced in practice, is that these programs are protective, actually. So not only when children and families come into the programs as they're screaming, but also, you know, so it's easier to identify when a child is exhibiting symptoms of disordered eating or an eating disorder because they're highly engaged with the program and with the staff. 00:53:57:10 - 00:54:34:00 Unknown But also by teaching children and families about nutrition, and physical activity, and stress, and coping, and positive parenting, and wellness, and engaging with community resources and getting them engaged and all of these, you know, positive practices. It's really helping to protect, protect them, right. So these are protective. And so I think that we really want to get that message out there that actually we believe that engaging children and families in these lifestyle interventions will, will help to combat that issue as opposed to, promote it. 00:54:34:02 - 00:54:53:01 Unknown But, Sarah, do you have anything you'd like to add? Or Arianna? Just, two quick things. Agree with what you said. One is we just want to make sure it's very clear that the lifestyle programs that Doctor Goodman's referring to are evidence-based, high-quality lifestyle programs. Putting a child on a diet or giving a little nutrition recommendation in clinic is not what we're talking about. 00:54:53:01 - 00:55:12:11 Unknown Those things could potentially be harmful. I just really want to distinguish that. And the second comment I'll make is that remember, especially for teenagers, the world that they are living in and they know that they have obesity, these kids all know. And so what they're doing otherwise is probably what they saw on TikTok or what a family member is suggesting. 00:55:12:16 - 00:55:19:22 Unknown And those are likely to be less healthy than what we're recommending in the evidence-based programs. So just wanted to make those two. 00:55:20:23 - 00:55:42:04 Unknown Okay. We are at 3:00. So I want to thank our audience for joining us. As a reminder, this will be posted after, we clean up the video on the website, so if you want to come back and see some of the great information or the practical tips that you heard today. And a huge thank you and audience, please join me in thanking our panel for such great information and we'll see you next time. 00:55:42:05 - 00:55:43:10 Unknown Thanks all!