associate professor and duly appointed in the division of gastroenterology and department of surgery at University of Michigan. She completed all of her postgraduate training at the Brigham and Women's Harvard Hospital System. She's currently the chief of endoscopy at Michigan and director of bariatric endoscopy. And she also serves as our chair of the Association of Bariatric Endoscopy. So welcome, Dr. Schulman. Thank you very much. And thank you to the course directors and the ASGE for having me today. It's really an honor to be here. So today I was asked to speak about endoscopic bariatric therapies, current options, efficacy and long-term outcomes, medical versus endoscopy versus surgery in 15 minutes. So I will do my best. These are my disclosures. So I wanted to start by just framing the magnitude of the obesity epidemic within the United States. This comes as common knowledge to many of us, but the rates of both obesity and severe obesity continue to increase. Every state has over 20% of patients with obesity. And as we know with the increases in obesity, we're seeing an increase in obesity-related comorbidities such as diabetes. And there's a whole plethora of management strategies that we've used to employ to try to help treat this epidemic including lifestyle strategies like diets and exercise, anti-obesity medications, and specifically the new second generation meds. And then a whole plethora of procedural options, both endoscopic and surgical. Typically endoscopic options for obesity are used in patients with BMI of over 27. And typically surgical options are used for patients with higher BMIs, but we certainly see some overlap there. It's important to know that as the efficacy of these procedures increases, the risk also increases. And so it's important to individualize therapy when you're thinking about endoscopic interventions. There's many other benefits to endoscopic therapies as well, including the fact that the majority of these are outpatient procedures. This is a really nice option for patients who are non-surgical candidates or to do not want surgery. It can commonly bridge a critical gap in obesity because it can target patients where BMI is a little bit lower. It's also been shown in numerous trials to be safe, repeatable, and potentially a bridge to another intervention like a knee replacement or a heart transplant. We also have a whole spectrum of small bowel interventions which are increasingly gaining attention and not currently FDA approved, but in many pivotal trials. And these are really designed to treat obesity-related comorbidities. And so the thought of being able to treat both the weight component with a gastric device and diabetes or NAFLD with a small bowel device is very attractive. So today I was asked to focus mostly on the endoscopic bariatric therapies. And we'll start by talking about the gastric specific procedures and then move on to the small bowel procedures. But I also wanted to just quickly mention the pharmacologic treatment because of course these second generation anti-obesity medications have really exploded over the course of the last year. So starting with the gastric procedures. So these come in many flavors and this is very much an evolving landscape. So it's an exciting time to think about all of this but we're gonna start with the space occupying devices or the intragastric balloons. And we have seen many changes of these over the course of the last several years but these are FDA approved for patients with BMI of 30 to 40. And the ASGE considers patients with a BMI of over 40 to be reasonable candidates for use as a bridge therapy. One of the most common devices is a single chamber FDA approved commercially available device. There recently were also a dual system device and a swallowable device but neither of these are commercially available currently but still FDA approved. There's an adjustable type of balloon which is FDA approved but not widely commercially available yet although we're starting to see that that may become more available soon. And then finally, there's a device that's fully swallowable that passes on its own and obviates its complete need for endoscopy. The two I'm gonna just show you quick videos of are the two that I think will become or are already commercially available because I think we'll be seeing a lot more of these in practice. So the first is the single chamber intragastric balloon. This is a device that's easily passed into the esophagus under direct visualization and then into the stomach. And then once it's in the stomach it's filled with anywhere between 400 and 700 cc's of fluid. I usually put in a little bit of methylene blue just so that in case for any reason the balloon leaks the patient's urine will turn blue. And then eventually after it's filled you just pop it off the catheter. So very quick and very straightforward. The second device you can see here is the new adjustable intragastric balloon. And so it looks very similar to the original one I just showed you, but in this case if a patient's having symptoms you can remove fluid or if the patient is not gaining or losing enough weight you can add fluid to it. And so when we look at the pivotal studies that led to the original FDA approval you can see that the percent total body weight loss at six months was somewhat variable but somewhere between seven and 15%. There's certainly a component of the knowledge of subject assignment that may play a role in some of the lower weight losses especially because patients tend to achieve much more weight loss in clinical practice. We think the mechanism of these is very much dependent on delayed gastric emptying. And so what a few studies have shown is that once the balloon is explanted you lose that delay in gastric emptying and maybe the weight loss isn't as durable as we would hope. But it also may lead to some of the symptoms that patients may experience with these. The fluid-filled balloons classically have led to a slightly higher rate of early removal and patients will commonly have nausea or vomiting, reflux or abdominal pain early on but more severe adverse events are very uncommon. I just wanted to show you a video of a patient who we saw at University of Michigan who had had a balloon placed abroad about two months earlier. And you can see here a case of hyperinflation. And so the balloon, you can see an air fluid level which is very suggestive of this entity. You can see an abnormal contour of our abdominal wall. And you can start to see the concern for perforation or impending perforation in the gastric wall with air. And when we went down into the stomach you can again see that this is completely colonized with both a fungal organism and also bacterial organism. So we looked at what the impact was of intragastric balloon on comorbidities. And we actually found in a meta-analysis of about 40 studies with almost 6,000 patients that patients do have quite impressive improvement in obesity related comorbidities. And this led the AGA to really put out their practice recommendations which were in those seeking weight loss failed, who had failed conventional therapy, the use of intragastric balloon with lifestyle modification was recommended over lifestyle modification alone. They also list, as you can see here, listed a series of other recommendations in those undergoing intragastric balloon placement which I'll skip for the sake of time. And then after removal, it's really important to maintain lifestyle interventions. Next I'm gonna move on to the gastric remodeling procedures and these have really grown in excitement and popularity over the last several years. There are three different types of gastric remodeling procedures. One of which uses the endoscopic suturing device known as the endoscopic sleeve gastroplasty. You can see this on the far left. The two other procedures, including both pose and the endomena placation are more placation devices. And so you can see there's somewhat different methods and different techniques that are employed, but overall very similar final picture. You can also see that despite these different interventions, the weight loss is very consistent in clinical trials and very impressive ranging somewhere from about 12 to 18%. So I'm gonna spend the most time talking about the endoscopic sleeve, as this is the most kind of ubiquitous procedure that we've seen across the country. And this is a procedure where full thickness sutures have been placed to invaginate the entire greater curvature of the stomach. And these extend from the incisora to the GE junction. This creates a narrow luminal sleeve with a small fundic pouch. And we usually leave the fundus alone, but it decreases gastric volume by up to 80%. And the original studies were done by Dr. Thompson's group at the Brigham and Women's Hospital, really kind of evaluating what is the best suture pattern of this new full thickness device. But where this field has evolved has most of the people providing this procedure offering what's called a U-stitch or accordion approach. And you can see in the pattern on the left, we usually start on the anterior wall. Then we place our next stitch above the greater curvature and then below the greater curvature and then along the posterior wall. And you kind of march back up the gastric lumen in a U approach. So you can see on the right, this was a procedure that I had about two weeks ago. Perfect timing for this talk. And we were making sure that every bite is full thickness. We know some of the original devices didn't have the same longevity because of the fact that the bites were not really full thickness, but you can see what we call a pink out. So we're pulling the tissue in very deeply and then taking deep bites. And this is what you can see at the end. It's a very narrowed gastric lumen. As I mentioned, we usually leave a small fundic pouch alone and that's for a variety of reasons. The fundus is the thinnest walled area or thinnest walled structure of the stomach and highest risk, but also we think a lot of the hormonal control stems from that. So what is the data for endoscopic sleeves? There was a large systematic review and pooled meta-analysis that demonstrated that at about 18 months or two years, the average weight loss was around 17%. And then many of you may be familiar with the kind of landmark trial in this area, which was a randomized control trial of nine centers called the MERIT study. They looked at percent excess weight loss at one year and then also secondary endpoints, including changes in metabolic comorbidities between groups. There were 85 patients assigned to the ESG group and 124 to the control group. And as I mentioned, they were followed for 52 weeks. And then patients who were originally assigned to the ESG group could undergo retightening if they'd gained any weight. And patients who were originally assigned to the control group could undergo a crossover. And what I find most exciting about this slide is that patients who were under very aggressive, lifestyle management still only lost about three to 5% of their weight. But then when they were crossed over to the ESG group, they did just as well as the patients who were originally randomized to undergo ESG. And this was enough to lead to FDA approval. As I mentioned, there's two other placation devices that I think we'll start to see more and more commonly. These are very exciting. And I think we're going to see a lot more data from these. One study that I really enjoy that came also from the Brigham and Women's Hospital is its effect on regression of hepatic fibrosis. And so these were patients who underwent placation interventions. And you can see significant improvement in hepatic fibrosis. And the newer study showing improvement in portal pressures as well. I'm going to spend just a minute talking about small bowel procedures. And these are very much designed to treat the comorbidities of obesity and specifically diabetes. So we know that obesity is a disorder of energy homeostasis. Enteric neurons of the proximal small bowel play a major pivotal role. And there's really several theories to explain the metabolic and neurohormonal response related to obesity and related comorbidities. I don't know if anyone was at our session this morning, but very complex interactions that include both a foregut and a hindgut hypothesis, but both really rely on the reduced production of an unidentified proposed signal or an anti-incretin that promotes insulin resistance. So diets high in fat and sugar alter the duodenal structure or function. And this in turn alters nutrient sensing and signaling to the brain. And so this leads to a duodenal endocrine hyperactivity and ultimately metabolic diseases. And so many of these duodenal therapies are really designed to improve glycemic control by altering the gut non-invasively. These are the three that you may see in existing pivotal studies. We're part of the first two. On the far left, you can see the duodenal resurfacing therapy. The idea behind this is basically burning the duodenum. In the middle, you can see a sleeve liner or lining device that basically covers the duodenum. And on the far right, you can see a very unique and interesting technology where magnets are deployed and basically create alternative diversion pathways in really an incisionless anastomotic technique. So I think we're gonna be seeing more and more of these. Massive guideline just came out between the ASG and the ESGE looking at all of these therapies as a whole. And I would strongly urge anyone with interest in this field to take a look at it, although it is about 100 pages. So make sure you get to keep time to read it all. And then finally, I'm just gonna briefly mention pharmacologic treatment. We used to think of obesity as kind of a segmental approach, kind of a stepwise approach as well. You start at the bottom with lifestyle interventions, then you offer medications and then you offer endoscopic therapy. And if people don't respond, you go to surgery. And I think we're seeing more and more that there's not only significant integration of these techniques, but also different mechanisms by which they work. And so there's very much synergy that we've been able to see between the techniques. I'm gonna spend the last minute and a half talking about pharmacotherapy and specifically the second generation meds. So glucagon-like peptide one receptor agonists are known as the GLP-1RAs are increasingly used for the treatment of diabetes and their mechanism really mimics incretins, which are hormones released after eating. So they prompt glucose-dependent insulin release from the pancreatic islet cells, they stimulate satiety centers, they inhibit glucagon release. And as many of us who do endoscopy are familiar, they diminish gastric emptying and have been the hype of much anesthesia and GI overlap in the endoscopy units recently. I don't have time to review all of the efficacy of these, but they have very impressive results and the percent total body weight loss is somewhere between 15 and 25% depending on the trial and the medication. They lead to glycemic control, weight independent cardiovascular risk reduction and appetite suppression. And my oldest had to help me with this slide, but I was shocked to see that one of these meds was the single biggest search term on TikTok with over 270 million views. And of course we have many celebrities using these meds which have led to intermittent shortages. These come in many flavors with different routes and different administrations and different half-lives, but we have seen recently that combining these medications with intragastric balloons or endoscopic sleeve really have a synergistic effect. So there's potential for an improved mechanism and we really expect to see these increasing combination therapies moving forward. So in conclusion, bariatric endoscopy is a rapidly growing field with many new and evolving devices. With growth brings the potential of simplifying these interventions and really broadening their adoption. Gastric procedures are here, small bowel procedures are coming and combination therapies like gastric and small bowel are certainly on the horizon to treat both obesity and its comorbidities. Medication management will obviously play an important role and a synergistic role, but all of this should be performed in the context of a comprehensive multidisciplinary center. Thank you so much.

Dr. Schulman

endoscopic bariatric therapies

obesity epidemic

gastric procedures

small bowel procedures