We have a great treat for you guys today. Obesity is a very complex disease that ACE really wants to focus on. Adiposity-based chronic disease, it's driving a lot of the things that we need to really treat and get control of. So we have to personalize therapy, and we have a real star-studded team today for you to talk about some of the therapeutics, from medications to some of the procedures and surgeries to help our patients treat their obesity and adiposity-based chronic disease. So first up, I'd like to welcome Dr. Barm Abu Daya. He's a professor of medicine, director of advanced endoscopy, director of metabolic and bariatric endoscopy, consultant in gastroenterology and advanced therapeutic endoscopy, and vice chair of innovation and commercialization at the Mayo Clinic in Rochester, Minnesota. He's also the chair of the Bariatric and Metabolic Endoscopy Committee of the International Federation for the Surgery of Obesity and Metabolic Disorders, and co-chair of the Bariatric Committee of the American Foregut Society. Come on up. Thank you. Thanks. Good afternoon, dear colleagues. It's a distinct honor and pleasure to be with you talking about endoscopic devices and procedures for the management of obesity. These are my disclosures. So the reason we're talking about endoscopic procedures and devices is because in 2022, we're still having a significant unmet need in the management of excess adiposity and obesity. Right now, about 1% of patients who qualify for bariatric surgery get such an intervention, and about 1% also of those with mild to moderate forms of the disease get a pharmacotherapeutic intervention for their excess adiposity. So obviously, we need to keep augmenting the spectrum of obesity care and introducing multiple devices that are safe and effective, organ sparing, have little long-term consequence to health, and is minimally disruptive to the patient lifestyle. Patient acceptance of such intervention is an important factor in scalability of the interventions and the management of this disease. So the spectrum of care should be something like that. You enter the spectrum of care based on the severity of your disease, and you graduate or you keep moving down the spectrum based on your response. So patients should be managed for this chronic disease at their lifetime, during their lifetime, with multiple interventions applied either in sequence or in tandem. We're gonna be focusing about endoscopic interventions for obesity and metabolic disease, and we're gonna split them anatomically, those that work on the stomach and those that works on the small intestines. So the interventions that target the stomach work by augmenting human appetite, and appetite is separated into satiation and satiety. Satiation is governed by the accommodation of the stomach. This is SPECT imaging of the fasted and fed stomach, and you could see that the entire stomach accommodates, conveying signal to the afferent vagal nerves in order to terminate that meal. Then you pursue your next meal, and that's governed by the process of gastric emptying. So in essence, these gastric interventions either affect the accommodation or the emptying of the stomach or both processes in order to allow patients to consume low-caloric diets without feeling miserably hungry. These come in different flavors. There's space-occupying devices that come in the form of intragastric balloon. There's four intragastric balloon in the U.S. market. There is gas-filled, fluid-filled balloons. There's single and double balloons. There's adjustable balloons, and now we're gonna have a swallowable balloon that is in clinical trials. Balloons are a technically easy intervention. Patient is under light sedation. You introduce the balloon as you would do an orogastric or a nasogastric tube, and this is one of the single, fluid-filled intragastric balloon filled with about 650 cc of saline. You could see that once you deploy the device, you dissociate the valve, and the device stays in the stomach for an indwelling time of about six months to a year. This balloon is indicated for six months use in the United States. We also have adjustable intragastric balloons that allow for adjustability to enhance tolerance and to treat weight loss plateaus as well, and these have longer indwelling time. And now we'll also have swallowable balloons that do not require endoscopy for placement or retrieval, and these are currently in pivotal U.S. clinical trials as well. As a group, there's been multiple randomized open-label and sham-controlled trials in this field. All these trials are from the U.S., pivotal trials, and you could see, collectively, intragastric balloon results in about 10 or more percent total body weight loss as a group of devices, and this is significantly more than lifestyle or sham arms in these clinical trials. This is the most recent publication in The Lancet of the adjustable intragastric balloon. It was a large, multicenter U.S. trial showing about 14% total body weight loss at eight months after balloon implantation. Given the advantages of the balloon as a weight loss strategy, in combination with a lifestyle program and behavioral intervention, now societies are recommending their use for the treatment of excess adiposity and its metabolic complication, especially NAFLD and type 2 diabetes. The other category of devices that work on the stomach are those that augment intermittent fasting. We all know the multiple metabolic adaptation to intermittent fasting and the important role of that strategy on metabolic health. However, following appropriate metabolic fast is difficult because people get hungry and they do not follow the fasting program as scheduled. Therefore, there is a second class of devices, which are implantable prostheses, that enable patients to follow intermittent fast because these devices are caloric agnostic. You do not need food in the stomach to activate the mechanisms of these devices. This prosthesis is an umbrella-shaped prosthesis that exerts pressure on the cardio of the stomach, activating mechanical receptors that convey vagal signaling to the brainstem, thus indicating fullness without the need for food. However, we should and continue to push the envelope with endoscopic bariatric and metabolic interventions. Implantable devices do have limitations. They're temporary devices. They come with a period of accommodative symptoms until the body gets adjusted to this foreign object in it, and they require multiple endoscopies in order to administer therapy. Therefore, there's significant momentum into the field of gastric remodeling technology to allow us to enhance the durability and the tolerability and the scalability of endobariatrics by using devices that have more durable response. The endoscopic sleeve gastroplasty is a procedure that was developed at the Mayo Clinic in 2013, and it uses a per-oral, full-thickness endoscopic suturing device to imbricate the greater curvature of the stomach from the level of the incisora, or the antrum, to the proximal body. You could see that the stomach now is decreased in volume, and the accommodation of stomach is altered, and so as the emptying, thus it affects both the accommodation and emptying, allowing patient to follow a restricted caloric diet without feeling hungry. This is functional MRI of the endoscopic sleeve six months after the procedure. You could see the advantage of such a procedure. It preserves the anatomy. You don't have to lose your stomach. It preserves the vascular and the nerve supply of the stomach, so the stomach is functioning normally, it's just a smaller stomach, as you could see from these MRI images. Another similar procedure that augments the process of satiety and satiation through remodeling the stomach is this per-oral obesity surgery endoscopic using the incisorless operating platform. It's creating a similar anatomical manipulation as the endoscopic sleeve gastroplasty of the suturing, but it's using these plications that are reinforced with these netonal baskets in order to tubularize the stomach, creating a shortened and tubular stomach that augments the process of satiety and satiation. This is the radiographic images of the stomach before and after the intervention. You could see the stomach is much shorter and much narrower than before, and these are the correlate endoscopic pictures of the procedure before and after as well. So again, now these are, we're talking one intervention, outpatient procedure, takes about 30 to 45 minutes. Patients are out and about with their daily life, and now this single intervention that is done as an outpatient results in about 17% total body weight loss at one year with a single endoscopic outpatient procedure, and this is a meta-analysis of about 1,700 patients from different countries across the globe. Another large study of about 1,800 patients with the endoscopic sleeve gastroplasty in Brazil showed a total body weight loss of 18% at 12 months with a very low incidence of serious adverse events at 0.8%. There is now a U.S. multi-center randomized control trial that included both surgeons and gastroenterologists both in community and academic practice. The first phase of the trial was presented at the IFSO meeting last year, so I'll present the result for you. The full trial will be presented next week next door in the convention center during Digestive Disease Week. It was 208 patients among the nine U.S. centers with class one, class two obesity. It's designed to meet the endpoint defined by ASMBS and ASGE, the governing societies of success, defining success as 25% excess weight loss at one year with a delta compared to a moderate intensity lifestyle of 15%. We extended this to look at durability at two years and the impact on comorbidities. This is the randomized portion of the trial. You could see that the primary endpoint was reaching 25% excess weight loss. The ASG arm reached double that, about 50% excess weight loss at one year. The second co-primary endpoint was a delta compared to a moderate intensity lifestyle of 15%. It really significantly met that endpoint with a delta of 45% excess weight loss. 77% of those who underwent the procedure were responders reaching more than 25% excess weight loss at one year with a total body weight loss of about 16.3%. Second part of the trial was affected by the COVID pandemic and the negative impact it had on clinical trials and weight loss. However, we were very pleasantly surprised to see those that crossed over from the first level of the trial or from lifestyle into ASG almost reach an identical weight loss at two years compared to the primary ASG in year one. And those who got the procedure in year one maintained the vast majority of the weight loss at two years despite the pandemic. So now we're gonna shift gears a little bit and talk about small intestinal interventions. And the small intestine is really the second brain. You could see the deep nerve interventions of the small intestines. This is the submucosal plexus of nerves. And through endocrine enteric nervous system signaling, the duodenum is really the orchestrator of the metabolic response. It's tasked to response to the glucose load that comes to it and arrange the metabolic response that happens afterward. We know that in states of type two diabetes and metabolic stress that this orchestra conductor gets inefficient in processing these signals and therefore there's a state of insulin resistance. So there's a lot of focus on utilizing the power of the duodenum for treatment of metabolic disease such as type two diabetes and fatty liver disease to reverse the metabolic clock on this organ. There's technologies that use heat modality to resurface the superficial mucosal layer of the duodenum thus affecting endocrine signaling of that structure. And there's also now technologies that not only do the resurfacing of the mucosal layer but now could reset signaling in the enteric nervous system in order to recapture metabolic health using athermal modalities that through an energy modality called electroporation or pulse electrical field. In essence, we are electrocuting the duodenum through an outpatient procedure by only for a nanosecond without generating heat in order to treat diseases like type two diabetes. So there's a lot of interest in these modalities moving forward. Now the future is gonna be combination. We have a procedure that results in about 18% total body weight loss at one year now with durability up to two years. Now we have effective medications such as the GLP-1 agonist. Could we combine them in order to treat the disease of excess adiposity for a long period of time? This was the subject of a randomized controlled trial where 60 eligible patients underwent in step one the endoscopic sleep gastroplasty. At the one month mark of the procedure, patients were either randomized to a semaglutide or to placebo and they were followed for an additional 11 months after the addition of the semaglutide. Here is the graphs of the two group. You could see those who underwent endoscopic sleep gastroplasty alone reached about 19% total body weight loss at one year. Those who got the combination of the endoscopic sleep gastroplasty and the semaglutide reached about 25% excess weight loss. So to me this is exciting, but more exciting is what about using them in sequence? So have the endoscopic sleep resulting in 18% total body weight loss at two years and now introducing semaglutide to maintain the weight loss between year two to five. That would be a very appealing strategy moving forward. So you could see if we plotted percentage or probability of reaching more than 10% total body weight loss, which is the clinically significant weight loss, you could see that now with the state of the affairs in 2022 we have really nice spread of procedures, medications and surgeries that could augment the spectrum of care to serve patients suffering from the disease of obesity. And again, reaching this critical threshold of weight loss results in significant metabolic benefits. This is a randomized controlled trial published in the New England Journal of Medicine that looked at the effect of 18% total body weight loss whether achieved by surgery or by lifestyle modification alone. And you could see that using a hyperinsulinemic euglycemic pancreatic clamp, the benefit was identical. The level of glucose control, insulin levels, beta cell function and the other parameters were also identically similar between the two groups. So I will conclude with a plea to start looking at management of obesity as a different paradigm in 2022. And the paradigm should be focusing on two fundamental strategies. One is putting the disease into remission and then maintaining their remission. We've all been dealing with a very frustrated patients who have been trying to live their life losing weight. They lose four pounds and they gain back six. They try to exercise and then their joints are hurting and they cannot follow the exercise. So the cliche of eat less and exercise more is not sufficient in 2022. We need to break through the vicious cycle and produce significant weight loss that makes the patients look better, feel better and engage in a healthy living program. So this weight loss paradigm should involve pharmacotherapies, endoscopic procedures like balloons and endosleeve and surgery. Once we get rid of the weight in this sprint of weight loss, then we have a captured audience who are engaged in healthy living and would be willing to listen to healthy living where lifestyle and behavior should be the cornerstone of maintenance of that weight loss. Pharmacotherapies have a big role and endoscopic devices in sequence or in tandem could have a role as well. And those who have weight regain or now could be ready to graduate to bariatric surgery as well. So in conclusion, the GI tract is front and central in weight and metabolic regulation. Endoscopic bariatric and metabolic therapy will play a major role in the management of obesity and its metabolic complication. The future is bright with multiple innovations in the pipeline, but the key is to have a new paradigm in looking at excess adiposity and treating it such as any other diseases that we need a treatment that is effective over the lifetime of the patient. And with that, I thank you for your kind attention and we'll be entertaining questions at the end of the session. Thank you. All right, good job. All right, thank you very much. That was outstanding. And I think it shows a lot of us not only the complexities of obesity and how we need to treat in multimodal fashions, but also that a lot of us have to step up our PowerPoint presentations. All right, Dr. Tarana Salamani is an associate professor in Department of Medicine at Penn State Hershey Medical Center. She's an obesity medicine specialist and fellow at the Obesity Society. She specializes in strategic program development for optimized obesity care and operational efficiency. And she's gonna talk about medical management after surgery. Welcome. Thank you. Thank you so much and I agree with you. I do have to up my PowerPoint presentation now. So it's good to be with you today. Thank you for having me today. I'm gonna be talking to you about the medical management of obesity post-bariatric surgery, but particularly focusing on anti-obesity medication. These are my disclosures. And here are the objectives. So today we're gonna talk about identifying weight regain and insufficient weight loss post-bariatric surgery, understanding the role of anti-obesity medication in post-bariatric surgery patient population, and touch on what are the factors that we should be keeping in mind we are selecting one of these anti-obesity medication in our post-bariatric patient population. So there's no question that bariatric surgery is quite effective in delivering the most amount of weight loss for us long-term in a very safe and an effective way. But certainly patient post-bariatric surgery do still struggle with obesity. And this is why I often tell my patients that obesity is a chronic and relapsing disease and it's kind of getting a bariatric surgery is part of their weight management journey, but certainly the disease has to be managed even after bariatric surgery. So patients who have had bariatric surgery, when they come to us after the surgery in form of a consult or as a new patient, they generally fall into one of the three categories. Whether they have had insufficient weight loss, or they have had weight regain, or they could be a patient that actually has done well with bariatric surgery. Let's say their BMI was at 53, but now their BMI is at 41, and they still need to lose more weight or they're interested in further weight loss here. So those are the three categories that they would actually fall into. I would say there's really no perfect definition out there yet for weight regain particularly, also some for insufficient weight loss as well. But I'll put kind of the variable definitions that we do find in the literature at this time. So insufficient weight loss is most commonly defined as less than 50% excess weight loss at 18 months. And in some literature it is said that, you know, you should look at it at 12 months. For weight regain, it can be defined as greater than 25% excess weight loss from the nadir weight, 10, 20 or 25% of the maximal weight loss being regained, or greater than 10, 15% of the nadir weight. And there was a recent publication that came out that actually looked at how much weight regain the patient is experiencing at a 30-day interval. So looking at as mild regain, defining it as regain of less than 0.5% of the nadir weight, moderate weight regain as being 0.5% to 1% regain from the nadir weight, and rapid weight regain as being regain of greater than 1% weight gain from the nadir weight itself. So there's a huge variability here. And the problem with that is that when we are seeing these patients in our clinic, the question becomes, well, when do we actually intervene? Is this patient in a weight regain? Or are they, you know, are they still in a plateau? You know, how do I make a decision? What do I do with it? And I think having a more standardized definition will certainly help us in helping the patient better in managing their obesity. So in terms of prevalence, again, the literature just does show a variable prevalence for both of them. But we do see weight regain in post-adjustable gastric band patients in about 38% of them, 27.8% of sleeve gastrectomy patient, and 3.9% of Rheum-Y gastric bypass patients. And insufficient weight loss has been seen anywhere between 32 to 40% of sleeve gastrectomy patient. And one study cited a combination of all of them together, they observed in about 20% of the patient there's insufficient amount of weight loss. I think it's important to keep in mind what is the outcome of this weight regain and insufficient weight loss, because undoubtedly we do see that and these patients do exist and they do come to our clinic for help here. I do think that these patient population are at high risk at failing the management of their disease here. And over time, they actually become quite non-compliant with their appointment or following the recommendations that are being given to them. And I think that non-compliant comes from kind of, it's due to several reasons. One is that because the individual feels that they're not going to be understood or they are blaming themselves and there's a significant degree of shame and guilt with them coming in. One of the common thing that I hear from patients when they come in, they'll tell me, well, I just thought to myself, what are you gonna tell me? You're gonna tell me to do the diet that I already know. You're gonna tell me to do the exercise that I'm struggling to do anyway. Or, you know, I brought it up to my provider and I told them that I was struggling with a hunger or not having the satiety that I was feeling right after bariatric surgery and they just basically told me to follow the same diet and physical activity. So I do think it's important to keep in mind why these patients become non-compliant over time and they have a poor adherence. And certainly, I think that leads them into kind of regaining their weight back, which really from a psychosocial standpoint put them at a very difficult situation. They do experience social isolation, anxiety, and depression, and of course, as the weight regain happens, there's going to be a relapse in their metabolic as well as mechanical complications of their obesity, which was previously treated with bariatric surgery. So the underlying cause of weight regain and insufficient weight loss is multifactorial. And I've tried to list them over here. It could be hormonal, coming from just kind of observing that there's that increase in the granule level and decrease in the PYY and GLP-1. It could be nutritional. Patients are experiencing more hunger, less of a satiety. They're kind of going back into grazing on food or they're just having a hard time sticking with the composition and the volume size of the food that has been recommended to them. Then there's a physical inactivity component of it. Certainly, COVID-19 pandemic hasn't been helpful with that. But I will certainly say one of the common thing that I see in clinic is that patients confusing lifestyle activity with physical activity. And when you are in a weight reduced state, post weight loss, physical activity is absolutely critical at moderate intensity to help the patient manage their weight better. So I feel like that's one of the things that we pretty regularly pick on during our evaluation and try to talk to the patient about. Then there are behavioral factors, and I will stress on the top one here, the relapse and lapses in healthy behavior. I think as human beings, we are often will have lapses or relapses in the positive behavioral changes that we're making, whether that is towards our diet or our financial problems or being more positive in life. But I think that it's important to kind of create that supportive environment to let the patient know that having those lapses and relapses are okay, but they have to continue to engage with them. And I think particularly the some of the GI procedures that we were talking about previously, as well as pharmacotherapy can really help the patients get out of these lapses and relapses. And there certainly could be anatomical reasons for patients experiencing weight regain or insufficient weight loss, as well as genetics. So what are the kind of the management strategies that we have in place as well as a prevention strategies, I think the first point here will not come to you as a surprise that the approach to managing weight regain and insufficient weight loss has to be multidisciplinary. You have to have an obesity medicine specialist in place, which could be an endocrinologist and internal medicine and OBGYN, someone who knows how to treat obesity. The metabolic and bariatric surgeon has to be involved. So as a dietician behaviors and an exercise trainer. But I brought this second point and I touched on this on my initial slide here, the importance of recognizing that obesity is a chronic disease. And that's because so certainly I think as providers, we recognize that but I often very surprised when I see post bariatric surgery patients when we talk to them about you, you know, experiencing that weight regain or having insufficient weight loss is not something abnormal is something to be expected. And even though in our center, we do educate patients when they are going for bariatric surgery, I often find that patients really have a hard time coming into terms with it, accepting it or kind of knowing why is it happening to them and kind of be because that essentially does can prevent them from being able to manage their disease better long term. In terms of treatment option, what is available, it's bariatric surgery revision endoscopic procedures that has been touched on, and anti obesity medication as well as reengaging with lifestyle modification. And I will be focusing on anti obesity medication today. There's no question that anti obesity medication is the least invasive way of getting ahead of weight regain and insufficient weight loss. And I will say it can actually help the patient reengage better with their lifestyle modification. So what are the FDA approved medications for chronic management of obesity? Orlistat, fentramine to pyramid extended release, which is Q-Semia, bupropion and naltrexone, which is Contrave, loracletide, which is Accenta and semaglutide, which is Vigovi. And the two medications that are not FDA approved, that Dr. Loftin will be touching on are terzapotide and vimagrobat. So what do we know about the utility of these anti obesity medication in the post bariatric surgery population? I'm going to go through a couple of studies that has been well published and talked about. This was a study that looked at 319 patients who experienced weight regain or insufficient weight loss. 258 of them had roan Y gastric bypass and 61 had sleeve gastrectomy. And they actually looked retrospectively into their health records to see which one of these 15 medications were actually used on these patients when they were experiencing weight regain and insufficient weight loss. As you can see here is that a little bit over 50% of the patients were able to achieve greater than 5% weight loss. 30% was about greater than 10% weight loss and 15% of the patients were able to achieve greater than 15% weight loss. So there's a heterogeneity of response to this into anti obesity medication use after bariatric surgery, which should not be surprising to us as this is the case, I think with any type of a medical intervention. In this study, what they showed was that topiramide was statistically significant, did much better compared to other medication in terms of delivering on weight loss, and patients who were put on topiramide were twice more likely to achieve 10% weight loss compared to other patients. In the younger population that was between the age of 21 to 30, they found that topiramide and fentramine both performed quite well and patients did well with them. Certainly the patients that has had Roux-en-Y gastric bypass, they did better with anti obesity medication, particularly if their BMI was much higher prior to bariatric surgery. Other findings that they had is that individuals who had obstructive sleep apnea, they did not do too well with the anti obesity medication in terms of the amount of weight loss that they were actually able to achieve here. This was another study, as you can see, the number is quite small 37 young adults aged 21 to 30 years of age who have also undergone Roux-en-Y gastric bypass and sleep gastrectomy experiencing weight regain. And they looked at three medication that were evaluated on these patients topiramide, fentramine and metformin. And I think you'll see a very similar result to the previous study, again, that a little bit more than half of the patients can actually achieve greater than 5% weight loss. And then you have 34% that are achieving about 10% and 23% of them can achieve greater than 15% weight loss. What they found is that metformin did not do the best really the fentramine and topiramide performed the best compared to metformin. And I think this should not be surprising, because in the previous study, they had also found that in a younger population, fentramine and topiramide do really well in terms of weight loss. The other thing that they had saw in this study was that if the medication was initiated a plateau patient did much better, compared to if they were started on the medication at the time of when they have regained a significant amount of their weight. So I just want to pause here and make one point here, if a patient had regained 50 pounds back compared to a patient had only regained five pounds, both patient had lost about 7% weight loss. So the amount of weight loss that they had achieved was the same. But when you look at it cumulatively from their highest weight or BMI prior to bariatric surgery, patients who were started on medication at the time of plateau did much better, which really highlights the importance of doing early intervention post-bariatric surgery for weight regain. This was a study that looked at 117 patients that were included in this analysis, you can see the breakdown of what was the brain-wide gastric bypass, gastric band and sleeve gastrectomy. And these individuals had regained their weight, their average BMI that they had entered into this study was anywhere between 42 to 48. And they had only evaluated one medication on this study, which was loracletide 3 milligram approximately about eight years post-bariatric surgery, this patient was started on loracletide and the results was actually quite positive. The patients did quite well in terms of their weight loss. And what was interesting about this is studies that the patients were able to maintain that meaningful weight loss one year out post their weight regain. This is another study that looked at only 25 patients. And as you can see, the studies are not very large in terms of their number, there's not a whole lot that has been done in looking at the utility of anti-obesity medications post-bariatric surgery. In this particular study, they actually looked at multiple medication and the use of multiple medications in managing weight regain or insufficient weight loss after bariatric surgery. And what they found is that when you use more than one medication, and particularly including the one that are acting on the CNS, patients tend to do much better in terms of weight loss. So to sum this up, weight regain after bariatric surgery is not uncommon. I think what is more and more what we're seeing is being defined is that the moderate weight regain, which is greater than 15% weight regain from the total amount that has been lost, does take place between 25 to 35% of individuals about two to five years post bariatric surgery. So it's not it should be expected. And I think when you see the patient, I think letting them know of what we know about the data and what is out there, it will certainly put them at a more comfortable place and makes them feel like okay, they are ready to go ahead and combat the disease. Anti obesity medication is certainly beneficial in addressing both weight regain and insufficient weight loss. And unfortunately, what we see is that most of the time patients are started on medications after they have experienced weight regain, not at the time that they are actually have hit the weight loss plateau. There is limited research on the use of anti obesity medication post bariatric surgery. And I think this the number of the participants in the studies that I've showed nicely demonstrate that. And also, we don't know a whole lot yet as to when should we start the medication? How much weight regain should the patient actually accomplish? Or what is the definition of weight loss plateau that should then trigger us to initiate the medication? And really, what is the best medication to use here? Certainly, there are some studies that have shown that patients with lab band and roomwide gastric bypass tend to do much better with phentermine to pyramid, naltrexone and bupropion. But then when you study the arachnotide on the sleep gastrectomy, roomwide gastric bypass and lab band patient, the arachnotide does really well for all three of those categories. So something to keep in mind here. The ideal time to initiate anti obesity medication post surgery is at the nadir weight or when the patient hits the plateau. Anti obesity medication that are initiated after weight regain has been shown to achieve lower cumulative total amount of weight loss. Post-operative bariatric surgery patients that are treated with two or more medications are going to have a much better outcome. And we should certainly assist the patient in optimising their lifestyle modification so they can do better with these anti obesity medications. And it's important to consider the anti obesity medication side effects, kind of what are the contraindications that they have. And I think as many of you I'm sure would agree here, we often have to find out what the patient's coverage looks like before we can consider any of these medication and we kind of have to get creative with that. And when an effective anti obesity medication is working on the patient, don't stop it. Even if the patient stops losing weight on it, it doesn't mean that it's not working. I think that certainly has been well demonstrated in individuals that we are doing lifestyle modification anti obesity medication when we stop the anti obesity medication, they are actually regaining their weight better and they're not doing so well with their weight management. And I'm sure we will see the same thing in post bariatric surgery patients. So once that right medication is found for that right patient, keep the patient on it. Even if they are have stopped losing weight, let's say six months out or nine months out, it does not necessarily mean that the medication is no longer effective for the patient. And with that, I'm going to go ahead and stop here. Thank you. Thank you very much. And I hope that was very thought provoking and how we have to embrace obesity and adiposity based chronic disease, the chronicity of it. And we can't let clinical inertia get in our way for that early intervention and really achieve not just our weight response goals of therapy, but our our clinical response goals of therapy in a complication centric manner. So that's that was great. Dr. Theresa Lemasters, diplomat of the American Board of Obesity Medicine in 2019. She's the UnityPoint clinic weight loss specialist in West Des Moines, Iowa, and the Iowa Methodist Medical Center. She has a comprehensive accredited center there. Dr. Lemasters currently serves as the president elect for the Executive Council for the American Society of Metabolic and Bariatric Surgery and will proceed on to serve as president of ASMBS in 2022. And she's going to talk to us about metabolic and bariatric surgery. Thank you. All right. Thank you so much, Dr. Naglowski. Can I get my slides up? Great. All right. Thank you all for coming out and listening today when the weather is so beautiful. I'm excited that you're here and I think we have some great things to talk about. So I get to talk about something I'm very passionate about the metabolic surgery for obesity. These are my disclosures and they shouldn't impact my talk a lot today. We're going to talk about how bariatric surgery impacts mortality. Who's a candidate for bariatric surgery? Just a little bit about the procedures and then what is the future of bariatric surgery? So what we understand is that obesity is really a disease of the brain. It's a problem with the way the body is regulating appetite, energy expenditure and the way it stores fat. And this is a complex interaction between gut hormones and the nervous system. And what we also understand is that people with the outside phenotypic appearance of obesity do not all have the same underlying mechanism for how they got there. Some of these patients have had obesity since they were three years old. Some it came on much later in life. It is not all the same disease. But why do we care? Obesity leads to death. Mortality is death. We know it decreases life expectancy from anywhere from 5 to 15 years. So what about diet and exercise? We've already heard some about that. But this was a very good randomized control trial that demonstrated intensive lifestyle behavior therapy, people really, really, really trying harder with a lot of help. And how did it impact these outcome measures? Well, they found after 10 years, they had some modest weight loss, but they did not impact the risk of death from cardiovascular disease and cancer. So here's the real question. Why should we consider metabolic bariatric surgery? We're trying to answer this question. Can we change this future? Can we save lives? And I'll tell you the answer is emphatically yes. 29 studies demonstrate the improvement in mortality, that surgery can decrease mortality. There's a survival benefit for those who undergo metabolic bariatric surgery. So this is a recent study in Jack that demonstrated the benefits in the Medicare population, those over 65 and those under 65, with 37% lower risk of death, especially from heart disease, stroke. The Swedish obesity study was a prospective controlled study demonstrating patients with surgery versus medical treatment, 29% decrease in the hazard ratio for death. The Adams study demonstrated a decrease in all cause mortality by 40% for those having surgery. This meta analysis in the Lancet recently demonstrated substantial survival benefit to metabolic bariatric surgery with 50% lower risk of death, 50%. Medium life expectancy gained average of six years, but those with type two diabetes, the ones that we all are seeing and treating gained 9.3 years. What's really impressive here is the number needed to treat to prevent one death in patients with diabetes, eight. That's very impressive, powerful data. International Diabetes Federation put out a statement more than 10 years ago that said we need to look at bariatric surgery for type two diabetics at a BMI of 35, and even consider it with those down to a BMI of 30, who have significant disease. Why? Because we know that earlier we treat type two diabetes with surgery, the better chance we get in placing those patients into long term remission. When we look at the Asian population, the Indian ethnicity population, we need to decrease our BMI targets, because their level of disease is much higher at a lower BMI. Many, many, benefits to metabolic bariatric surgery across all different systems. But a big one here is quality of life improved in 95% of patients. So what we've really come to understand is this is metabolic bariatric surgery. It is not about restriction and malabsorption. What we are doing is we are changing biochemistry. We're doing this through gut hormones, and that different procedures impact these different hormone pathways differently. So these are the main procedures that are performed today, all laparoscopic, most common by far are the sleeve and the rheumigastric bypass. I'm not going to talk about these a lot. But just to understand that the lap band is a band placed around the top of the stomach and works through those vagal afferent nerve pathways. So it doesn't alter these gut hormones. It's adjustable and removable. It doesn't have bowel connections and the weight loss is 15 to 20% percent. The sleeve gastrectomy is the number one procedure worldwide for a lot of reasons. With this procedure, I remove three quarters of the volume of the stomach, but it's really not about the small stomach. I'm taking out the majority of the ghrelin producing cells. So it suppresses hunger substantially. And then I change the gut hormones in a very similar way to the rheumigastric bypass that connect to the brain. So patients are much more satisfied on those smaller portions and their metabolism is improved. We don't alter the bowel connections, but very good treatment of type two diabetes. Weight loss is usually 20 to 30% of total body weight. And the reason this is so popular is it's very well tolerated by patients. We do have to watch out for some patients who have severe GERD or it can cause some new reflux in some patients. But this procedure works well for many, many patients, high risk patients. They can live with this procedure. The rheumigastric bypass has been around for over 50 years. Now it's been updated 14 times. So it doesn't look a lot like it did 50 years ago, but we know this is very effective for type two diabetes. Great treatment for reflux. Weight loss is 25 to 35% total body weight. Why is it not number one? Because there's some known downsides. There's a higher risk of ulcers, bowel obstruction, reintervention, higher risk of vitamin deficiencies, and it takes more active participation by the patient to avoid self-harm. Then we end up with the biliopancreatic diversion of duodenal switch. All I'll tell you about this is it's definitely a more complicated procedure. Excellent weight loss, excellent treatment of type two diabetes, but very difficult for patients to live with long term. Lots of loose stools, sometimes eight to 10 loose stools a day, higher risk of vitamin deficiencies as well. So this can work well if you have the right patient, but they have to be extremely compliant. The SADI is a modification of the duodenal switch that's newer, a little bit better tolerated, but still significant risks here. So what we've really come to understand in the last five to 10 years is again, it's not about restriction and malabsorption. It's about the interaction of gut hormones with the nervous system in the brain. And that these different procedures impact these pathways differently gives us a target for manipulating these systems or a target to fine tune our approach. So why is surgery different than just putting the patient on a very low calorie diet? Well, we're actually able to reset the body's idea of normal lower the set point. We actually can't do that with medications, diet, the set point stays elevated, but with surgery, we can set it lower. And we do this through blocking those gut hormones. But I tell patients we don't cure obesity with surgery, we're treating a very severe chronic progressive disease, and it's very powerful. I can move that set point lower, but I cannot make it back to ideal, I cannot make it like you never had this disease. So I tell patients, you know, I'm impacting about two thirds of the connections between the gut and the brain. That means one third are still abnormal. And this disease is going to progress over your lifetime. And we need to continue to treat it. Now, some patients will say, well, I want my weight to be lower, can I just try harder with diet and exercise, if I want to get it lower? And the answer, unfortunately, is no, because the body is very sophisticated at defending that new set point as well. And we're going to talk a little bit more about what the last presenter talked about. There is a variable response to treatment with any treatment we do with all the medications we use for anything. And this is true for bariatric surgery. So this group did a great job kind of putting together a growth curve for bariatric surgery with the mean one and two standard deviations off the mean. And what they found is that even 16% of roomwide gastric bypass patients would fit into a poor responder category. All, let me say this again, all patients are going to have a weight change over their lowest weight or their nadir. It's part of the natural history of this chronic progressive disease. So weight change over the nadir is not abnormal or unexpected. But we need to define when this is pathologic. So we need to talk about realistic outcomes, not dream outcomes. So can we alter the patient's response to surgery? And you already heard a great talk. So the answer is yes. And how do we do that? We use medications. So we're able to target those individual pathways and fine tune our response to the individual patient and how they respond to surgery. So I'm actually not going to talk about this because our other presenters are talking about the medications. But when we step up our interventions, we have better weight loss, better comorbidity control, and the trade off is an increased risk of complications. And this is certainly true with surgery as well. As you move over to the right, better treatment, higher complication rate. So the trick is to find the balance and the right fit for the individual patient. That's why number two and three there are the most popular by far. They work very well, but still excellent safety profile and patients can tolerate them. Surgery is very safe. The risk of complications does vary depending on the procedure, but mortality is very low. We're talking one in 3,000. And in many practices, it's even lower than that. This really is as safe as a patient having their gallbladder out. So when they're afraid of surgery, and you ask them, would you be afraid of getting your gallbladder out? They'd be a little nervous, but probably not afraid. That's the way we need to talk about bariatric surgery. So when we talk about is a patient appropriate for surgery and which procedure should they have? It's actually many, many variables that we look at. And it's a shared decision making process. I tell everybody there is no one tool that is perfect for every person. We need to understand the patient, we need to individualize our treatment. So here's the big important question. When should patients have referral for bariatric surgery? We know that the patients with a BMI over 40 have a very low chance of maintaining enough weight loss to improve their comorbidities without surgery long term. So those definitely need to come to surgery. BMI over 35, many of those patients should come to surgery. We have lots of therapies we can combine too in these ranges. When we're at a BMI of 30, and they have type two diabetes, we really need to be considering surgery because type two diabetes especially is very impacted by how early we intervene in that disease with surgery. So if we can catch them in their first five to eight years of disease, we have the highest rates of remission. So Asian and Indian descent, they can be considered for surgery down to a BMI of 27.5. And again, earlier treatment is better. Don't wait till the patient's at end stage disease, because then I'm just pulling them off the edge of a cliff. If you send them to me earlier, we can transform what their life is like. The key here was already mentioned by the last presenter. This is a chronic disease. That means the long term care is the key to success. You cannot have surgery and think you're done and there's nothing else. There are contraindications to surgery. These are in the slides. So for the time sake, I'm going to skip by those. There are lots of myths out there about bariatric surgery. So what's the truth? How successful is bariatric surgery? Well, one out of 10 will regain most of their weight or all of their weight several years after surgery. Two out of 10 will gain a significant amount. Maybe they lost 100, 120 pounds, gain back 40 or 50 pounds. What we find is that group, their weight came up, but very rarely did their comorbidities and their metabolic burden come back with it. So they're still better off than they were. Seven out of 10 don't gain significant weight back. They were able to maintain that same similar weight loss long-term past 10 years. So that means nine out of 10 people who have metabolic bariatric surgery are better off than if they didn't have surgery. How does that compare to conventional diet and exercise? 95% will regain back most or all of their weight by three years. So we have to weigh what are the alternative options. So when surgery is so powerful, why don't more people come to have bariatric surgery? Well, first of all, people don't really understand how severe this disease is, how life-threatening, how disabling this disease is. They don't know what are the most effective treatment options. We actually did a survey and found out in the public, the number one way they think is the best to lose weight is doing diet and exercise on your own without even help from medical professionals. We know that is the least effective option, but there's a disconnect between what the public understands and what is true. There is stigma around patients with this disease and them seeking treatment for this disease. And there is fear. They're afraid of surgery, but they're afraid of failure. They're really afraid. They go through surgery and they still fail. Weight bias is really important. This is rampant, not just in our society, but also in our medical professionals. The number of people I hear say, well, the patient just wants a magic pill or they just want the easy way out. And I say, you know what? This is not the easy way out. This is the hard way out, but it does something they cannot do on their own. It changes their body to work with them, not against them. Now how long do people think about surgery before coming into surgery? Three years. So there's already a significant delay of seeking this treatment. And the problem with misunderstanding this disease is that when people think this is a voluntary or behavioral problem, it's a willpower problem, then surgery seems like an inappropriate treatment. And if they overestimate how effective diet and exercise is, or even medications, then they think that surgery is much more risky than it actually is. So the future really is an oncology model. We need to use neoadjuvant therapy, surgery, adjuvant therapy. Guess what? Some people's disease is going to recur or progress. They need repeat therapy, combination therapy, reoperative therapy, and a few of them. And these are the updated recommendations. We need everything as a yes and. We need to start much earlier in the disease at that BMI of 25 to 30. At 30, we need to consider surgery, especially if they have type 2 diabetes. At 35, we definitely need to be considering surgery. And at 40, surgery is really, really, really strongly indicated. So surgery is the most powerful tool we have, and we need to be prepared to wheel it. So I hope I've helped you understand that surgical treatment is really safe, effective, and durable long-term. And that early intervention with surgery actually leads to the best outcomes. So thank you for your time and attention. I look forward to our discussion later. Thank you. Thank you so much, and certainly highlighting the strong need for us to work in a multidisciplinary fashion to treat this complex disease and help battle that vicious cycle of stigma and diagnosis and not getting the therapy that they need and how these treatments are not mutually exclusive and we all need to work together better. All right. And last but not least, Dr. Holly Loftin is the Director of the Medical Weight Management Program at NYU Langen Health, where she serves as Clinical Associate Professor of Surgery and Medicine and continues to serve as the Fellowship Director of NYU's Health Clinical Obesity Medicine Fellowship. And she's going to talk to you about obesity pharmacotherapy and the future and what's on the horizon. Thank you very much. It's not quite time for Q&A, but we're getting there. That's what the slide says. So my topic today is pharmacotherapy, the present and the future. And I do intend for the slides to be available for you to use as a clinical tool. So I won't go through all of the different contraindications or potential side effects, but please know that these will be available. And my disclosure slides somehow disappeared. My disclosures are that I received research funding from Eli Lilly and Nova Nordisk and also speaker honorary and consulting funds from Nova Nordisk. So I think it's important to note, as many other speakers have earlier today, that pharmacotherapy for weight management is considered an adjunct to lifestyle therapy. And as we go through these slides, we can see the different amounts of weight loss achieved with the lifestyle modification, as we saw in Look Ahead, but they vary depending on the intensity of lifestyle behaviors. So I implore you as physicians, as providers, to consider a medication in addition to lifestyle. Even when a patient says, I failed that medication, really delve into how much lifestyle they were able to use in conjunction with that medication to achieve their goals of weight loss. So if I were doing this slide about 15 years ago, it would be very short. It would be this. This would be the slide for the entire presentation. And I'll talk about some of these older medications, as well as some of the ones that have been available in the last 10 years. So we'll start with the class of sympathomimines, amines, which have different names here. We have Phendimetrazine, Phentermine, Dianthopropion, and Benzphetamine. These are our classic appetite suppressants, what our patients tend to call weight loss drugs, weight loss pills. Some call them speed. They are not speed, I tell patients. That's not what your doctor gave you in the 90s. But these are still currently available medications that are scheduled drugs. And again, as our patients have follow-up for their nutritional lifestyle assessment, these medications do need to be prescribed with caution because of the potential for hypertension, tachycardia. Some of the contraindications are any type of CVD, previous MI, stroke. And so you may not consider this for your patients who are older or have high risk factors for cardiovascular disease. Potential side effects include elevated blood pressure, tachycardia, and some patients can have anxiety. I'll move on to Gastrointestinal Lipase Inhibitors, commonly known as Orlistat. This medication is available both over-the-counter and through prescription at different strengths. And the mechanism of this medication is the patient takes a capsule with a fat-containing meal and the lipase is inhibited. Thus, the patient is able to absorb about 70% of the fat in that meal and the other 30% is deposited in the stool. Now you can imagine the side effects of this would be those likened to steatorrhea. Patients have oily stool, sometimes uncontrollable diarrhea, gastric upset, and this is why sometimes patients don't tend to tolerate this medication. But as those of you who are in practice and using these medications for weight management and I'll talk about later, many times our prior authorizations require that we explain why we've not tried this type of medication before we're placing them in some of the newer classes of medications. And I really use that information to ask the patient, do you think you would tolerate a medication with these side effects? Would that be conducive to your life? And many of them answer no and were able to jump over that hurdle. So I'll move on to our more recently approved medication, the last 10 years. You can see 10 years ago, even as recent as last year, we've had some newer agents. And here you see the results of the sequel trial for Phentermine Topiramate ER. And think back a few slides to the Phentermine potential side effects. These are the same. And we've added now Topiramate to allow the patient to still achieve appetite suppression and more satiety but with lower likelihood of the tachycardia, palpitations, elevated blood pressure because of the mechanism of the Topiramate. So we saw about 11% weight loss with varying doses of this medication. It tends to be well tolerated. But some of the side effects tend to come from the Topiramate. Patients experience paresthesia to the extremities and some have cognitive dysfunction. So I do forewarn the patients that if you start to have word finding or you have a problem memorizing things, it may be due to that potential side effect of the medication. And if that's present, then we may reduce the dose or discontinue the medication. As well, I want to point out that this is contraindicated in Glaucoma, uncontrolled hyperthyroidism because of the Phentermine aspect, but also in women of childbearing potential who are not using any birth control method. There is a great risk, five times greater risk of cleft palate in the baby who's born to a mother who is taking Topiramate. So it is really highly recommended that mothers who are considering, potential mothers that are considering taking this medication beyond two contraceptive methods, a barrier and a hormonal. I'll move on to Naltrexone, Bupropion. So again, another combination medication. And you'll see these combination meds are being more likely to the forefront because we know that obesity being a chronic relapsing disease, we turn off one pathway and the body turns on another pathway to counteract that weight loss that was achieved. So the idea behind this is the Naltrexone is an opioid antagonist. And that actually sort of sits in the area that makes the patient crave certain foods and decreases that craving, as well as the Bupropion, though it does have some beneficial effects of boosting the patient's mood. The Bupropion actually affects the Alpha MSH pathway, which can help with satiety. So you put these two together, a patient has more satiety, decreased cravings, and we see the weight loss that you see here. Now I want to point out the outcomes of two trials that were done with this medication. Again this is a combo medication, but these components are both in one pill, and I'll go through the dosing in a few minutes. So we see the Greenway trial, and what's interesting is the placebo in Greenway's trial lost about 2% of their weight, but in Tom Wadden's trial the placebo lost 7% of their weight. So again, the intensity of the behavioral component is very important in the long-term outcomes. So with the Greenway trial and the lower dose of this medication, there was about 7% weight loss, which is similar to the placebo in the Wadden trial, but overall we saw about 8-12% weight loss with this medication. Again here you have the mechanisms, and the dose titration is very interesting. I think of it as 1, 2, 3, 4. The first week is one pill, the second week is two pills, the third week is three, and the fourth week is four. This is done to minimize the risk of nausea, which is the number one reported side effect, and this can be altered depending on your patient's tolerance of the medication. These are some of the, again, side effects, usually GI. This medication is contraindicated in uncontrolled hypertension, which is important to note, usually due to the bupropion aspect, and in patients who have risk of seizures, this medication has to be titrated down because of the bupropion component. Another important thing to think about with this medication in particular is the potential for interaction with many other medications. The activation of the cytochrome P system with the bupropion makes it highly likely that another medication could increase the concentration of the bupropion, or the bupropion could lower or increase the risk of another medication. An example I've had this many times in my clinic is I have patients who are on aromatase inhibitors, who are gaining weight, but have a need for that medication because they have breast cancer history, and this medication would not work well with the bupropion component because it could actually lower the concentrations of the aromatase inhibitors. Moving on to loraglutide. I'm sure everyone in the room is very familiar with loraglutide. If you weren't before this weekend, I'm sure you are now. This is a GLP-1 receptor agonist, and we find this to be very effective in weight management at different doses that are available. Of course, coverage is an issue, and you can see the titration there. It's three milligram dosing is really indicated for weight management, and I should say three milligram daily dosing for weight management. And here you see the outcomes of the scale trial. This is in kilograms on the y-axis. So the placebo group lost about four kilograms, and what I want you to see here is that those four kilograms were mostly lost in the first eight to 12 weeks of their intervention, receiving lifestyle, diet, and exercise. Now what you see with the bottom line here with the upside-down triangles, loraglutide three milligrams, not only did the patients lose 12 kilograms on average, but the weight loss proceeded for an average of six to eight months. And this is a crossover study you see at week 52. The placebo group received loraglutide three milligrams, and they all ended up around the same place at two years. And I'll also point out the green line there you see is oralestat, which it was compared to. So because this is a GLP-1 receptor agonist, the side effects are mostly gastrointestinal related, the nausea, constipation, some patients have abdominal pain and vomiting. And again, you titrate this medication as tolerated by your patients, and it's important to point out that the medication is contraindicated in those with a personal or family history of medullary thyroid cancer, such that in my practice, I have patients who say I have thyroid cancer. My family, I have them call that family member and find out what type during the visit. If they have papillary thyroid cancer in their mother, sister, brother, we proceed with this medication because that is not the contraindication. Again with regards to pancreatitis, pancreatitis is a rare potential side effect of this medication. And if pancreatitis is confirmed, the medication should be stopped and never restarted again based on the label. And we do see hypoglycemia, usually in patients who are already taking meds that can cause hypoglycemia such as insulin secretotox. So it's important to make sure that as we're ramping up the dose of the GLP-1 agonist that we're lowering the medications that could also cause hypoglycemia because the indication for those meds lowers as the patient is improving their weight loss. So this is a newer class of medication that I won't say the brand name of. It's cellulose citric acid and it's actually a controversy whether this is a medication or a device. And the way this medication is taken by the patient is they're instructed to take it twice a day, usually with their biggest meals, usually lunch and dinner. And they take these capsules and drink water and wait about 30 minutes before they have their meal. These capsules then form with the water a gel in the stomach and it has a consistency of chewed vegetables. So before the patient has even taken any food, they have the feeling that they've eaten a lot of vegetables and that can help with their satiety and thus they have a lower caloric intake. The gel then naturally dissolves in the stomach and leaves through the GI system. So this is an available FDA approved medication slash device for weight management that is available through the company's own specific providers and you can see the weight loss was about 5% which is greater than placebo. And lastly, semaglutide 2.4. This is the weight management approved dose. This medication became available in June 2021 to Much For Joyce and it has some issues with production right now. We look forward to that ending soon. And this is basically another GLP-1 that has very strong affinities to the GLP-1 receptors. And this is a weekly injection, self-administered by the patient and we see the weight loss are 10% or 12% with others. We see about 18% weight loss. And another point I want to make clear here is the weight loss goes on for quite a long time. With this step study, you can see that patients start to plateau around one year and clinically I've seen patients continue to lose weight for even two years. And you see the great effect of most patients are getting 5% weight loss and we're getting about 40% of patients getting 20% weight loss. So very effective. The side effects are similar to the other GLP-1 I mentioned earlier. Now I'll move on to some medications that are for specific patient populations. And what I want to point out here is the other meds really are targeting GLP-1 receptors in the arcuate nucleus of the hypothalamus, targeting lipase, targeting our appetite centers that are more downstream for the paraventricular nucleus. But there are certain patients who have genetic mutations which cause them to have very limited satiety. And this can be noticed as early as age three. So these affect more the MC4R pathway. This medication is setmelanotide, sorry for the error in the alignment of the name there. But this medication is a MC4R receptor agonist. And basically in patients who are determined by genetic testing to have a POMC deficiency, leptin receptor deficiency, or PSK1 deficiency, these patients don't get the maximum effect from the other medications because there's basically a hole in the pathway for satiety. So this is very much more downstream and is able to basically fill that hole so the patients can maintain satiety and they have a new way of feeling when they eat. This is a daily subcutaneous injection against similar side effects to the GLP-1s. But because this stimulates the MSH receptor, there can be some hyperpigmentation. So people do notice a tan. And then when they have moles or nevi in their body, they tend to get darker. That does discontinue if the medicine is discontinued. So I'll talk about some of our newer medications quickly. Here's some data on SGLT2 inhibitors, which are, of course, available in practice. And we see varying degrees of weight loss with these medications. And actually, with the various DAPA, Canna, Imfothagazine, in addition to Phentermine, we've seen about 7 kilogram weight loss, which is greater than any of that that you see here with this slide. So I do want to point out that that's something that's in the pathway, coming up, and as well as Terzapotide. So when our slides were due, this data was not out, but Terzapotide is a GLP-1 combined GIP agonist. And this is a weekly injection as well. So we've experienced delayed gastric emptying, very similar pattern to the GLP-1s. But the initial thing that's very unique about this is that this is proven to increase energy expenditure. And, again, side effects, nausea, vomiting, diarrhea. Initially, I only had the trial here to tell you the weight loss, but this Surmount trial demonstrated 22.9% weight loss in these non-diabetes patients. And lastly, Cogrelantide. This is an amylant analog, which is being investigated alone and in combination with some Maglutide for weight management. Again, patients feel fuller longer, they have greater satiety. Again, a weekly subcutaneous injection. The weight loss is similar to some of the other medications that I mentioned, but when you can think of combination. And many patients need multiple medications because of the bypass of one pathway, and the body puts another pathway back in order so that it can gain weight again. So in combination with some Maglutide, this is going to be one of those medications that I think will change the game for weight management. And it's been very effective and proven to be even greater than our Liraglutide. And thank you. Thank you so much for that talk, and more support for getting us all to utilize these underutilized therapies, from pharmacotherapy to procedures and surgery. So now I get to be like George Stephanopoulos with my powerhouse roundtable. So I invite you to come up to the microphones. I can't see you, so I don't know how people do this. Oh, there we go. All right. First one's up. This is a question for Dr. LeMaster. So you mentioned the barriers to surgery. And the biggest one in my practice is cost, or coverage, or lack of coverage. And so we have an excellent local program where I practice in Southeast Idaho. But nine out of 10 of my patients come down here to Tijuana and get their sleeve. And almost every one of them, I can say everyone, have had an excellent experience. They get good care. It's very professionally done. And they come back and lose weight. And they just do just as well as my patients who have the program in my hometown. And so the question is, is that legitimate? And the second question is, what's being done to get our payers to invest in prevention? Because that's the biggest barrier in my practice, is lack of coverage. And also with WeGoBe, when it first came out, we could use it when anybody wanted to, because it was $10 a month. And I had all these people who were non-diabetics lose weight. And then a year later, it went on formula, and it's $1,000 a month. And they all came off and gained their weight back. And so it's sad. We have this molecule that could be so much more used, and yet we can only use it now for our type 1 or our type 2 diabetic patients. It's limited because of lack of coverage. Yeah. So that's a big question. Very complex. We'll try to boil it down a little bit. Access to care is always an issue. Where does access to care problem come from? From bias. From thinking that this disease is a lifestyle or willpower choice. The more we can move the needle on people understanding obesity is a complex physiologic disease, the more we'll move the access needle. Because that includes for medications and for surgery. The payers have to really understand this as a complex progressive disease to get there. Access for surgery is better than it used to be. But I worked on access to care for 15 years, and we're still not there. It's very patchy. So medical tourism is also very patchy. Some have a good experience. Some have a terrible experience. The number that we take care of that had a terrible experience is significant as well. But multidisciplinary care is really important for the long-term care of this disease. And we do a lot of work for preparation of patients before they ever get to surgery, and preparing them for, as was mentioned before, what's going to happen later? What are the expected outcomes? This is not transactional. Surgery is one piece. It's important because it changes the physiology in a way we can't do with other things, but it's only one piece. And we have to move the needle on access, and I think medications is part of that. As people understand the use of medications, that helps them understand this as a disease and why surgery is important as a disease. But right now it's discrimination against people who have this disease accessing the life-saving treatment that they need. So unfortunately, I have these huge signs out here that says we're going 52 seconds over our time limit. So unless the second person in line over here who's going to be our president-elect has some power above my pay grade can get us to keep talking some more. I think unfortunately we're out of time, but this was a great talk, multidisciplinary talk, and I hope it encourages everyone to keep working on this for us and improving the care for our patients with this complex disease. Thank you. Folks, come ask us questions over here.

obesity management

adiposity-based chronic disease

endoscopic interventions

post-bariatric surgery care

gastric interventions

weight regain

anti-obesity medication

mechanisms of action

sympathomimetics

lipase inhibitors

GLP-1 receptor agonists