So, we'll move on then to the next talk in this session, and that talk is by Steve Edmundowitz, who is going to transition over to endoscopic therapies. Steve is a professor of medicine at the University of Colorado, where he directs the endoscopy program there. And he's going to talk today about where endoscopic bariatric therapies fit into the obesity treatment paradigm. Steve, thanks for joining us. Good morning. I hope you can hear me, Lee, and I hope everything's going well. My topic for the day is where do the endoscopic bariatric therapies fit into obesity treatment? And I do have a few disclosures that I wanted to show for a minute, some of which are in the obesity space. So, I think this slide is extremely telling when you look at the world impact of obesity and where we have come from in the last three decades. Clearly, this is as much a pandemic as other pandemics that we are facing. And unfortunately, there is no vaccine at this point in time for the obesity epidemic. For those of you that like to follow the CDC data slides with the images of the United States, I put these two together showing the perceived or self-reported obesity indexes in 2011 and now in 2019, which is the most recent data. And as you can see, despite everything we've been trying to do with the obesity epidemic, we are failing. It's also interesting that Shelby and I practice in one of the few states that has been able to maintain an extremely low obesity index. And that's probably because of nothing we have done, but more the lifestyle issues of our colleagues here in Colorado. I should mention that despite that, the incidence in Colorado is still one in five patients, so probably one of the highest incidences of disease of any disorder that we could talk about. So, in terms of therapies for obesity, it's pretty clear that we need every effective therapy available to be deployed in this population. We need to understand the costs of not acting in this population. And we have to recognize that patients in general, in many times, are just avoiding us. There's been little recognition in circles that obesity is a problem. And part of this is all the work we've been doing to convince and associate with our primary care physicians to identify patients that are becoming obese and giving them options in terms of how to evaluate and treat these patients. Many of you in this call have participated in the Weight of the Nation conferences back in 2012. There's been a recent meta-analysis that also looked at the incidence and the cost of obesity and the management of these disorders. And again, these costs that are on this slide are very difficult to estimate, and they probably don't include all the costs of the associated malignancies, heart disease, other complications that are associated with obesity, that if we do not act, we are going to see the burden fall on the generations to come. Now, the previous lecture has very nicely delineated the lifestyle therapy and pharmacotherapy options for our patients with obesity. And it's clear to me, having been in this field for some time, that that really is the base of our, essentially, our care for patients with obesity. And there are many patients that respond to these therapies, but those responses are not always continued. And there are some patients that just avoid lifestyle therapy in general. There's no other therapy that can be implemented, in my opinion, without some basic lifestyle therapy, and perhaps without some pharmacotherapy in conjunction with it that will be effective in the long term. Because as Dr. Kaplan just mentioned, this is a chronic disease, and the therapy will need to be chronic. However, there are some alterations of anatomy that we can perform, and there are some other mechanisms that Sai will talk about in the next lecture that can lead to continued weight loss or persistence of weight loss in our patients. And we should discuss those. Dr. Kaplan also talked about the treatment gap between surgery and the pharmacotherapy or lifestyle therapies. And while that treatment gap hopefully will be able to be bridged with agents in the future, currently it exists. And we have a major gap, not only in terms of our ability to treat or what these modalities can do, but we have a gap in what the patients are willing to do. There are also alternative therapies that are coming into vogue that may or may not have a role in this space. And so all of these, looking together, have a tremendous ability to approach patients with obesity, but they have to be employed. They have to be deployed. And the reality is that there's hurdles, as was mentioned, in terms of just employing lifestyle therapy in patients with insurances. There's hurdles with patient compliance, and this continues to be a major issue. I want to just briefly mention the surgical therapies because this field has changed dramatically over the years as well. And if you look at the top of this slide, the invasiveness going from the adjustable gastric band all the way to the biliary pancreatic diversion surgery, you can see that there are marked changes in the anatomy and in the ability to go from a restrictive procedure to a malabsorptive procedure. On the table below, you can see that the incidence of gastric bands being placed is being reduced, largely because of complications we're seeing down the road of migration of these bands or problems with this condition. More and more bariatric surgeons are employing sleeve gastrectomy as their primary approach to patients, particularly those that don't have reflux, and perhaps those that don't have significant diabetes initially. The complications of these surgeries are sometimes difficult to track, but there is a significant complication rate. It's a mortality rate, and there are serious adverse events. They're not huge numbers, maybe measured in the less than 5% rate. But for patients, that can be significant, and the symptoms that occur after these surgeries can be significant as well. So that, in total, with the success that can be occurred with these surgeries, has planted a picture for our patients. And we tend to see the patients that have fear of complications or fear of surgery. They have issues with cost of surgery or the coverage they have. The reality is that the demand for surgery, if we were going to employ surgery more wildly, is probably the demand exceeds all possibilities of taking that number of people to the operating room. And we are seeing more and more weight regain after these operations that has become an issue in terms of management that you'll hear about later. The fact is that despite these modern advances and what I believe to be the safety and efficacy of surgery, less than 2% of patients with morbid obesity currently are being operated on. And that leaves a huge population that's essentially untreated. Again, the treatment gap, as Lee mentioned. And I do believe that there's a role for endoscopic bariatric therapies in that space. There's also the reality that despite the fact that we have effective lifestyle and pharmacotherapy agents, there's really been limited deployment of those in this population for various reasons. So the patients are really demanding a non-surgical option and many of them are not able to do this with lifestyle management and weight loss medications. So the concept of a non-surgical endoluminal or endoscopic bariatric therapy is that we're going to in some way modify the gastrointestinal tract. But we may require, and it may require a flexible endoscopic procedure. We would hope that the morbidity and safety of this issue would be better than laparoscopic surgery. We feel that these weight loss management issues may be able to be managed in terms of weight loss that is long lasting, but perhaps not as long lasting as what you would get with surgical therapy. And many of these therapies may be reappliable. You may be able to repeat the procedure or modify the procedure afterwards that will allow you to continue to get weight loss in your patient. So this is a list of the currently available FDA approved endoscopic bariatric therapies in the United States. And they fall into a couple categories. There are intergastric balloons. There's aspiration therapy that Dr. Kaplan mentioned as a modality. And there are modifications with the tissue apposition devices that are not really approved for obesity management, but they're approved for opposing tissue at this point in time. And this is primarily the endoscopic sleeve gastroplasty where we're modifying the stomach. And then there's another system that does a very similar approach with a slightly different anchor and snowshoe mechanism. What are our hurls to these endoscopic bariatric therapies? Well, probably the biggest hurdle we're facing right now is what everyone faces in the obesity management areas, the difficulties in getting coverage for our patients. Most of these therapies have been essentially avoided by the insurers, even though there's prospective data that looks very encouraging. They're deemed investigational. They're occasionally covered by some policies. So you do have to have an expert to look and see what your patients may be eligible for. And a lot of these therapies are, I would say, reasonable enough in cost that patients have elected to pay for them out of pocket. The fact, though, that that is the modality that many of these are being done, it greatly limits access to the millions of patients in need in this country. There's also a relative lack of physician training. There are a few big programs around the country that train people very well. But a lot of times, the amount of cases that are being done is really not enough to continually educate a new generation of physicians that can develop these practices and these procedures. And then developing them in their practice once they finish their training has been a challenge because of what I mentioned previously in terms of the insurance coverage, patient pay procedures, and the systemic support. So we really haven't had the impact that I think we could have in this country if we had had a more systematic approach to the endoscopic bariatric therapies. One of the criticisms of the endoscopic bariatric therapies is that there is not established long-term data and well-designed randomized controlled tiles compared to other therapies. This is changing. And as you can imagine, these are new technologies. So it takes a while to develop a body of data that is compelling. And as I look at the surgical literature, I'm finally starting to see data that makes me convinced that there have been long-term follow-up studies and randomized control trials that show that the surgical approaches to obesity have been, I'd say, proven. So where do these therapies fit in obesity management? I think they clearly have a role as an alternative to lifestyle therapy in patients who just either can't participate in that, refuse to participate in that, or have stalled in that therapy. But they also have a role to anyone who presents with obesity in terms of being exposed to this. And I'll talk about that a little bit in more detail at the end of my lecture. But the reality is that I think patients with this problem should have all of these options presented to them. And finding the right option for the right patient is as much a key to success as having a particular device or a drug that works. I want to talk a little bit about intergastric balloons because I think you've all seen this data in terms of the results of weight loss that can occur with balloons. These open-label versus randomized control data essentially show that the efficacy, if you look at the registry studies and other studies that have been shown afterwards, is about 10% total body weight loss can be achieved with the balloons over the period of their use and also over the period of the balloon withdrawal. Perhaps the most, I think, some of the most important data about the balloons is this trial that was completed in a fairly large population of patients in Greece back in the early 2010, 2012 era. What they showed is that they had fairly good efficacy with their program in terms of lifestyle management and balloons. And they were able to get pretty significant, by that I mean, excuse me, percent total body weight loss in the 10% range, 20% excess weight loss in their initial trial. And after the balloon was removed, many of those patients were able to maintain that for six months, as you can see in the second chart, second graphic. But as they're followed over time, the number of patients that could actually maintain that degree of weight loss diminished. Now, you could look at this as a glass half full and that at 60 months or five years, 20% of the patients were able to maintain the excess weight loss that they had accomplished with the balloon. But I think this brings a concern to most people that are in this space is that this is going to have to be either an adjunct to additional therapies or a repeated therapy, which it could be. So when I think of the other therapies that we're talking about, I want to look at the ones that could be essentially used in the treatment gap between pharmacology and surgical therapy. And I think that aspiration therapy is one that needs to be considered. And even though many people have had issues with this therapy, it actually can be a very effective therapy. And, you know, we are champions of this, Shelby Sullivan and our group at Wash U really started this process in terms of our open label trial. And we had very good results with this. In fact, we felt that this was an effective therapy and our patients that adapted to this therapy and actually used it did quite well. In fact, a small subpopulation of those patients actually were followed out to five years and they were able to maintain their weight loss without difficulty with this device. And I think this has been replicated in a number of early trials that have looked at obesity around the world and the use of this technique. It's not an expensive technique. It has some adverse events associated with it, as you would imagine with a G-tube, but it's easily deployable. And as long as the patients are compliant, it can be very effective. I think patients have to be the right patients. If you match the right patient with this condition and it's something that they are motivated to do and want to do, they will have a very effective therapy. It's relatively low cost of materials. All individuals, endoscopists that can perform essentially endoscopic gastrostomies can perform this procedure without much additional training. And I think it needs to have a place in our armamentarium of offering therapies to patients that they may like. I do think the patient and society acceptance may limit its use, but it is available and it is being used. I wanted to share now with you a couple of very nice case controlled studies that looked at the apposition therapy, particularly endoscopic sleeve gastroplasty, which will be explained in much more detail in the next lectures, and how this could fit in patient population. This was a very nice study from 2020 from the Hopkins Group showing how they compared their use of endoscopic sleeve gastroplasty to their essentially high intensity diet and lifestyle therapy, which in their hands is extremely effective. They were able to maintain at least 15% total body weight loss on average at six months and maintain that for almost a year. And when you compare that to what additional benefit you could get with endoscopic sleeve gastroplasty, there seemed to be some efficacy to the use of endoscopic sleeve gastroplasty over the course of the ESG procedure. So I think it has a role in conjunction with lifestyle therapy, but also in those patients that are starting to fail lifestyle therapy or won't be able to be effectively managed with lifestyle therapy. And if you look at their duration and continued weight loss for the patients that had endoscopic sleeve gastrectomy in the top line, that continued to almost 20% total body weight loss for a long period of time. Now we can argue about what amount of total body weight loss is necessary. I certainly agree that it does not have to be 20%, but that weight loss that can be maintained for a longer period of time without a major adjustment of the patient's ability to continue it or their lifestyle, I think is important. Reem Sirai also did a comparison case control study looking at ESG, the endoscopic bariatric procedure, versus laparoscopic sleeve gastrectomy and lap band in her population at Wheel Cornell. And she basically showed that there was less efficacy if you look at the data I pulled out in the corner, in the upper right corner. There's perhaps less efficacy in terms of total body weight loss at one year with the endoscopic sleeve gastroplasty, but still very respectable at 17%, slightly higher than the lap adjusted gastric band in their case control match group. But the adverse events were significantly reduced with less than 3% in the ESG population versus 9% in the lap band or the lap sleeve gastroplasty. So I think there is at least an inclination in this type of a study that these therapies are effective and they do have a less morbidity associated with them. Then in a similar case match study, the Hopkins group looked at the endoscopic sleeve gastroplasty versus the laparoscopic sleeve gastrectomy and essentially found almost the same data. They were able to show that they had a slightly reduced amount of weight loss, 17% again, which is very similar to what was seen in Ream's study, but also a markedly reduced adverse event rate compared to their laparoscopic surgery. They reported an adverse event rate of up to 5%. Versus 17% for the laparoscopic approach. So I think this does show that there's a role for these therapies and that they can fit into our management. My general opinion is I think you fit in anywhere you can get them to fit in. And it really depends on matching the therapy to the patient. In terms of cost, these are more expensive perhaps than lifestyle therapy over the long term. But in terms of durability and alternatives, they fit into the pattern of what we can do for our patients. And they can certainly salvage some patients. They're just unsuccessful with other therapies. So if you look at the initial pyramid therapy that we have, how do we deploy that in a reasonable way in our patient population? I think it's really important to have a group of individuals working together to identify the particular patient needs. And essentially to specialize or characterize the treatment for that patient. And that should include, in my mind, an obesity medicine specialist, an endoscopist, a surgeon, and then the extenders that have helped so much to have impact in this situation. The dieticians, the exercise specialists, behavior coaches, psychologists, even the nurse extender that's actually working with the patient or the patient coach, if you will, that works with them on a regular basis. And all of these touches will help us identify where the patients fit in the treatment algorithm. I think all of us would agree that starting with lifestyle management is very reasonable. To expand into pharmacotherapy if it's affordable and safe for the patients is reasonable. And then to be able to explain the differences between bariatric endoscopic therapies and surgical therapies and the benefits of each, I think, is extremely important. It's nice to do this in a multidisciplinary setting. We have the fortune of having a dedicated facility for this at our institution. And all of the centers and the people that are speaking today tend to work in these centers of excellence where you have the combination of individuals that I just spoke about. And I think in that setting, you can easily decide where your endoscopic bariatric therapies fit. I'd like to thank you very much for your attention this morning. It's been a pleasure to be here. And I do feel that the future for endoscopic bariatric therapies is bright.

endoscopic bariatric therapies

obesity treatment

global pandemic

lifestyle therapy

pharmacotherapy

surgical interventions