Hi, everyone. Good evening. It is my pleasure to be moderating and facilitating this very timely webinar on doping-blended medications and bariatric endoscopy. We want to thank the course directors, Dr. Pablo Demetrio and Dr. Shulman, for getting us together to discuss this. My name is Dr. Rushpreet Vani, and I am a triple board-certified gastroenterologist, and I am an interventional gastroenterologist and director of bariatric endoscopy at Mount Sinai South Nassau. I obtained my medical degree at SUNY Downstate in Brooklyn, New York, and completed my internal medicine residency at Montesquieu Medical Center in the Bronx. Our speakers tonight for tonight's webinar are Drs. Disha Narang and Dr. Jennifer Phan. So if all of you can just feel free to send us your questions via the Q&A feature on the bottom or the chat box, and we will definitely address all of them at the end of the talk. But to start, Dr. Disha Narang is a quadruple board-certified endocrinologist, obesity medicine specialist, culinary medicine specialist at Endeavor Health, North Shore, and director of obesity medicine. She completed her undergraduate medical training at Vanderbilt University before completing her internal medicine residency and endocrinology fellowship at the University of Chicago. Dr. Narang has a specialized interest in managing diabetes, obesity, and culinary medicine and strives to emphasize the adage, food is medicine, throughout her medical practice. Our second speaker, Dr. Jennifer Phan, is an assistant clinical professor of medicine in interventional and bariatric endoscopy at Keck School of Medicine of the University of Southern California in Los Angeles, California. She has a special research interest in obesity and bariatric endoscopy and works alongside multiple medical and surgical sub-specialties to further advance the field. She has published several peer-reviewed research papers in bariatric and advanced endoscopy in very well-known journals. So we are very excited, and Dr. Narang, take it away. Thank you so much for having me. I'm going to present the GLP-1's overview of weight management and mechanism of action. Okay, my disclosures, I'm on the Speaker's Bureau for ZupFound for Eli Lilly. So as we know, the prevalence of self-reported obesity has gone up very significantly in the last several decades, and we are seeing, as of 2030, we're expecting over 50% of our population to be in the obese category, which is above obesity by 30. And so we are in quite an epidemic at this stage, and this is where, you know, we see lifestyle, but then also from highly full. So as we know, BMI is very quality. So in females above a BMI of 40, we have 2.1 times higher mortality, and in males above a BMI, we see 2.4 times higher mortality. So over two-thirds of American adults are either trying to lose weight or maintain their weight, but only one-sixth of overweight and obese adults maintain weight loss of at least 10% for one year. So why is it so difficult to lose and maintain weight loss? It all comes back to our brain, and I always say, you know, in weight management, it's not our gut necessarily that contributes to all the weight loss, it's really our brain, and this is exactly where our therapeutics can have been highly valuable. So likely causes of weight gain. So of course, adherence, motivation to anti-restrictive regimens, of course, declines with time. I always say, you know, there's no special diet. It's always what can we sustain the longest and what can we be consistent about the longest, and that level of adherence tends to become very difficult over time, and that's why restrictive diets often are tough to maintain. And then, of course, hypothalamic injury. Weight loss does elicit biological adaptations that promote weight regain. So a decline in energy expenditure occurs, and of course, then we have an increase in hunger. So this is not a willpower issue. As you can see, there's just so many mechanisms and feedback loops and interactions between our adipose tissue, our liver, our gut, and our brain to cause weight gain and weight loss. So our hunger hormones. This is just a more zoomed-in version of that where we see interaction between our bowel, our adipose tissue, and our brain. And so satiety, weight gain, weight loss, and regain are mediated by a complex neuroendocrine regulatory system. So our hunger hormones are, of course, ghrelin, which stimulates hormones, you know, stimulates our food intake, and then our leptin is our inhibition hormone, and that inhibits food intake or creates satiety. So what leads to weight gain? There's several causes. Genetic factors, of course, environmental factors, medication, certain diseases like Cushing's syndrome, of course, lifestyle as well, the way we eat, our activity patterns, sleep patterns, stress levels, microbiome, yo-yo dieting, also our socioeconomic status as well. So the regulation of energy homeostasis is a complex process. And so that involves, of course, our central and sympathetic nervous systems, melanocortin system, nutrient intake, gut hormones, gut microbiome, and adipose tissue. And so as we increase the body fat, the amount of energy intake is greater than the amount of energy expenditure and which leads to weight gain. So why is it so difficult to lose weight? And I like this diagram because you can see as we decrease our calories and increase our activity, the expectation, of course, that we're going to lose weight. However, when metabolism, the hunger hormones, our fullness hormones kick in, that actually really causes weight regain. And so it's a constant tug of war between your efforts from a caloric and activity standpoint versus our physiology. And so as we lose our weight, growing levels go up and our satiety or fullness hormones decrease. And that's what drives people to have increased cravings. And then, of course, increased weight. And so that's exactly the mechanism of yo-yo dieting. So how do we turn this around? Of course, lifestyle. We have medications, therapeutics, and then we have interventions. So considerations for pharmacotherapy. We want to consider weight management, medical weight management, in patients who have a limited response to lifestyle modifications alone. So the indications to consider pharmacotherapy are a BMI above 27 with a weight-related comorbidity such as hypertension, hyperlipidemia, diabetes, heart disease, sleep apnea, joint disease, et cetera, or a BMI above 30 with no other comorbidities. So anti-obesity medications and their mechanisms of action. So as you can see, this is obviously a complex diagram, but all our therapeutics are interacting with these neurohormonal pathways. And so that makes it exciting time to be a weight management specialist just because we have more and more agents that are interacting with our hunger and fullness pathways or anorexigenic or exogenic pathways. And so these medications specifically are, again, like looking at where our interactions between the brain and the gut happen with these medications. And so our GLP-1 agonists, obviously the most popular these days, are the red dots. And so there's multiple areas where these interact, whereas some of our older agents, our oral agents typically interact mostly in the brain without any involvement with the gut. And as such, we see more weight loss over time with our newer agents because of both the gut and the brain interaction versus just the brain alone. And so these are, again, just a comparison between GLP-1 agonists and GIP. And so we see, of course, increased satiety, increased insulin secretion, glucagon secretion, beta cell proliferation, and a decrease in beta cell apoptosis. So that's where this becomes useful in diabetes management, of course. We also have an increase of nausea with GLP-1s, but a decrease of nausea with GIP in addition to delayed gastric emptying. We have a decreased production of hepatic glucose and, of course, increased insulin sensitivity. And then from the GIP standpoint, we see an increased lipid buffering capacity, decreased triglycerides, and increased insulin sensitivity. So this is exactly why it's been extremely useful to have these in the diabetes management world in addition to weight management. So the mean percentage weight change. As you can see, as we've gone through the various agents that have been FDA approved for weight management, we've seen greater and greater success with overall weight loss. So, of course, we're going to focus on this side of the slide today, looking at our GLP-1s in addition to our first GIP GLP-1 agonists. So this was a landmark study, the once weekly semaglutide in adults with overweight or obesity. So this showed up to just less than 14, sorry, just less than 15% weight loss over 68 weeks using semaglutide up to 2.4 milligrams. And beyond that, we had the SELECT trial, which showed significant cardiovascular outcomes in obesity without diabetes. And so just two weeks ago, actually, semaglutide was FDA approved for the treatment of people with obesity and a history of heart disease because we've seen a 20% reduction in major coronary events. And so this is extremely significant. Actually, today, this was approved by Medicare. This is the first anti-obesity medication to be approved by Medicare, especially given this data. So this is significant. And of course, this spans across all specialties. So not just cardiology and weight management, but this applies to every specialty at this point. This is also a significant development with terzapatide. So terzapatide is our first GIP and GLP-1 agonist. Terzapatide showed with the SIRMOUT3 trial, it showed above 23% overall weight loss. And so as of now, terzapatide is showing the greatest amount of weight loss of any of our agents. Looking at this, there's always the question, can we stop one of these agents after a certain amount of time and keep our weight off? And so this was the SIRMOUT4 trial. What this showed was that after 36 weeks, participants were split into placebo versus the treatment groups. The placebo off of terzapatide actually regained most of their weight. So sustainability is just as important as the initial weight loss. And that's where this is important because the question always comes up, when can we stop this? Well, as per this study, it's going to be tough to just take off the medication because, again, the suppression on the hunger hormone comes off and people will regain that hunger. The ghrelin levels will go up, and then you're going to see weight regain as you're seeing in these diagrams. So this is our current situation. It's unprecedented national shortages of our GLP-1s and now terzapatide as well. So we've obviously seen a significant social media presence of these medications. Everybody is talking about them. And so there's unprecedented national demand for this. And so what this has also amounted to is that there's lots of compounded substances out there as well. And so these are not FDA approved. We don't have safety and efficacy data on the compounded substances. And I would make sure to caution patients about taking compounded substances when we don't know what they're necessarily putting into their bodies. And so we'll see this often with online pharmacies, med spas, things like that. And already in the last several weeks, I've seen several patients that have very easily been able to get one of these compounded substances and start their therapy. We just, again, we don't necessarily know what the safety data for these is. So looking at overall the treatment, so lifestyle modification at best may provide about 6% weight loss. If we look at, again, meal replacement pharmacotherapy, with our current pharmacotherapy, we're seeing upwards of 22% to 23% weight loss. And then of course, as we get into endoscopic procedures, which Dr. Pham is going to go over in just a bit, we're potentially looking at equivalent, if not more. And so second generation AOMs, it's an exciting time to be a weight management specialist because we do have exciting agents in the pipeline. So ritatratide is supposed to be coming out in the next year to two years. Orfogliferone also is going to be an oral version of a GLP-1. And so we do have some exciting options coming up. And so, you know, the future is certainly bright for medical weight management therapies. I do want to make this point, though, that pharmacotherapy and surgical options, despite success rates, are only resources to weight loss. And so when I always say that it's really important to marry long-term lifestyle modification with pharmacotherapy or surgical therapy, because one does not exist without the other. And I've also seen a lot of people not succeed with pharmacotherapy if their lifestyles haven't changed. So at the end of the day, these are all resources. And a sustainable lifestyle still is highly, highly valued. So, you know, this is a change in the traditional paradigm. I often hear sort of the traditional advice, you know, eat less, move more. But that's not the same for everybody. And it's definitely not a one-size-fits-all approach to medical weight management. And so that's something that, you know, we really need to tailor towards the patients that we're treating. And so it's really important to understand that obesity is a chronic disease. It's really important to check our biases around obesity and the stereotypes associated with obesity, and then understand the physiology and pathology behind obesity and the genetic and environmental factors that might lead to weight gain. Patients who come in have often been judged or shamed for their weight for decades before they've come into clinic. And that could have been by, you know, people in their lives, but also the medical profession. So starting again, medication or referring to surgery or gastroenterology, it's not a failure in lifestyle management, but an adjunct. And so it's really, really important to continue ongoing lifestyle modification and therapy around that. And then the last is insurance providers need to start seeing obesity as a chronic disease. We're seeing so much backlash from insurance companies at this stage because coverage is minimal. Obviously, the cost of these medications is significant. And, you know, unfortunately, insurance companies these days are making up their own rules about what they're going to cover and what they're not going to cover and at what stage they're going to allow coverage. So final thoughts, again, anti-obesity medications are just resources to weight loss, just like surgical procedures or other devices. The success of medication depends on an emphasis on lifestyle, dietary recommendations, and appropriate cardio and resistance exercises. The success also depends on treatment of obesity as a chronic disease and not just a medication prescription. So this means that we are looking at long-term therapy. And then, of course, currently our late rate limiting step is insurance coverage in addition to a cost. And so that concludes my thoughts. And I will have Dr. Pham take over and feel free to follow me on social media to continue the conversation. That was a fantastic part one. Thank you so much, Dr. Narang. I'm going to share my PowerPoint. Okay, hopefully everyone can see this. So we're going to now take us to another step. So part two. So how does it fit within your bariatric and endoscopy practice? So the three goals of this part of the talk is, one, how do I incorporate this as a gastroenterologist? How do I incorporate GLP-1s into my clinical practice? How do I incorporate them when people have either bariatric endoscopy or surgery? And then what do I do with the adverse events that may happen with the initiation or continuation of GLP-1 medications? And so these are my disclosures. And so again, a quick overview, the indications for patients for GLP-1s. There's a wide indication and it's getting larger and faster, just as we had discussed for the uses of multiple obesity-related comorbidities. On the right, you'll see the FDA-approved medications to treat obesity in particular, not for diabetes, but these are the ones for obesity and so for long-term use. So when we're talking about kind of managing expectations for patients who are going to undergo GLP-1 therapy, there are certain other comorbidities that we should keep in mind that we can see as we start to lose more weight. So for example, if patients lose 3% of their body weight, we start to see improvements in blood glucose and triglyceride levels. If we have 5% total body weight loss, this is where we start to see an improvement in our HDL and cholesterol ratios and systolic blood pressures and hepatic steatosis scores by MRS and as well as quality of life functions. And this is really important because this is what innately a lot of patients are also looking for quality of life measure improvements, including symptoms of urinary stress incontinence, improvement in sexual function, as well as overall quality of life. This is where we start to undergo kind of changes in different subspecialties related to GLP-1 use. So 10% total body weight loss, this is where we start to see improvement in the NASH activity score as measured on biopsy or on OSA indices for sleep apnea. And at 15%, we start to see reduction in cardiovascular events, mortality, remission, and type 2 diabetes. So when we think about starting our patients on GLP-1s, we also need to think about what other things and what other comorbidities do they have that we also want to achieve either improvement of or remission of. So I like to keep these slides on because these are meant to be snapshots. So this is some of the GLP-1 medications. First, you see the type of medication on the left, the recommended dosing, as well as the escalation regimens in the middle, what dose adjustments need to be made in patients who have end-stage renal disease, and then precautions and warnings. And so these precautions and warnings are pretty unanimous and universal amongst the GLP-1s, but certain things to keep in mind are contraindications for family history of ventrilary thyroid cancer or MEN-2. And then we also see some of the contraindications or warnings in patients who have experienced pancreatitis or have gallstone disease, and we'll talk more about this in the next coming slides. So this here are the three older generations of GLP-1s. And then the next slide here are for terzapatide and senaglutide. Again, with the recommended dosing, the escalation dosing, any dose adjustments that are needed, as well as precautions and warnings. And happy to share these slides as a snapshot to anyone who needs them or would like them after the webinar. So how do I, as a gastroenterologist, incorporate GLP-1s into my clinical practice? So first step one are patient-centric factors. Are there any medications that cause weight gain? We want to be able to discontinue them if they're safe to discontinue, and a lot of these medications to think about are for either depression or antipsychotic medications that have a side effect profile of weight gain. Now we want to remember that GLP-1s may not be as effective when there's an inciting factor, including medications that could be causing weight gain. Are there hormonal factors that can cause weight gain, such as hypothyroidism or Cushing's disease or anything like that? You want to engage our endocrinologist in order to understand to make sure that there are no other reasons why metabolism or insulin sensitivity may be slowed. Are there contraindications to starting GLP-1s? Again, we talked about family history of medullary thyroid cancer, history of gastroparesis or pancreatitis. Next is what degree of weight loss is clinically needed. Remember, it's really important that if we start someone with a BMI of 30, it's very different from someone to starting someone with a BMI of 50 in terms of what their goal weight loss is in order to achieve a BMI, a certain BMI. So for example, this is the algorithm that I like to go to when looking at what degree of weight loss is clinically relevant and clinically needed here, and what is aligned with the patient's personal goals. So 5% total body weight loss, almost all FDA-approved medications will achieve this in their studies. Around 10% total body weight loss, fentaramine to paramate is a good anti-obesity medication to think about. If we're trying to achieve around 15% total body weight loss, the maglutide of the 2.4 milligram, again, this is the max dose for obesity, achieves this as an average in most studies. 20% total body weight loss, this is where we think about starting terzapatide. That, again, is the average weight loss seen in the 6 to 12-month benchmarks in the major studies. And at 25% total body weight loss, this is when we start to think of what was previously mentioned, ritaglutide, which is not yet on the market and not yet available outside of trials. And so we see here that the degree of weight loss is important when we decide whether we want to, you know, start ozempic or we want to start something like terzapatide. It's important to understand kind of what we clinically need and what is clinically relevant for each patient. The next is another really important patient-centric factor, is the patient willing to take this medication lifelong? And we already saw initial data here to discuss that when patients stopped terzapatide, that there was a significant increase in the percent body weight that was regained. And here we see the same issues that happen when patients stopped somaglutide. So in this step one trial, when it was extended beyond the 68 weeks and patients were randomized to continue somaglutide or not, we see almost a linear increase in weight to not quite the weight that they began with, but to a near weight that is not as significant as the weight that was lost while on the GLP-1. We also see reconstitution of some blood pressure issues as well as their hemoglobin A1c and inflammation marker CRP. Other thing to keep into consideration is how often patients are actually staying on GLP-1 medication. So this was an article out of Reuters that talked about how most patients on weight loss medications like somaglutides stop within a year. So at one year, 47.7% of patients discontinue their GLP-1s. Now, this again has already been alluded to. There are many reasons why patients may stop it, but again, up to 50% of patients stop their GLP-1s at this point in time. At two years, up to 70% of patients stop or discontinue their GLP-1s for whatever reason. So it's important to understand that not all patients continue these medications and whether that is an issue with education early on that we need to educate these patients, our patients that this is a lifelong medication, or there are other issues such as symptom profiles that they're experiencing or cost issues that they're experiencing or supply issues that they're experiencing. But regardless, these numbers are quite staggering. So again, the rate of adherence widely varies among studies, but are really high. And again, the reasons for discontinuation, up to 6% to 8% of patients will discontinue because of adverse events. And these are predominantly GI symptoms. Again, patient education, supply shortages and value versus expense, as on all insurance companies cover, these are very important medications. So this is where we go to the second goal of the talk is how do I incorporate GLP-1s in patients who have either undergone bariatric endoscopy or bariatric surgery? And as a bariatric endoscopist, these procedures are very near and dear to my heart, but there is absolutely an overlap when we discuss when and how to use GLP-1s. These are additive benefits. These are not meant to be one or the other, and that's very important to emphasize and to understand. So certain bariatric endoscopy procedures include volume reduction procedures. These include intragastric balloons and then volume reduction procedures such as endoscopic gastroplasties or outlet reductions, as well as plication devices with POSE or endomena. There are also malabsorptive procedures like the duodenal resurfacing or the shuttles and minors, but we'll talk about kind of the main ones that are in use right now. The first thing to remember is although GLP-1s are fantastic medications, not every patient will respond to a GLP-1. So the definition of a non-response is that you haven't achieved at least 5% total body weight loss in three months after initiating the medication. Now, when we look at the true trial data, so for example, somaglutide at their max dose, in a step one trial, up to 8% of patients were non-responders. In the step two trial, up to 26% of patients are non-responders. And for their trizepatide at 15 milligrams in instrument one trial, up to 30% were non-responders. So just as we know that obesity is a very complex disease process, so are people's responses to medication. And so what happens when patients don't respond to these medications? We look to things like bariatric endoscopy or bariatric surgery. So when do we consider starting GLP-1s if patients have undergone bariatric endoscopy procedures at first? So these include patients who are poor or non-responders to this therapy. So first we'll start with the FDA approved intragastric balloons. And these are space occupying balloon implants, and they're removed after six months. And they're FDA approved for a BMI of 30 to 35 with at least one obesity associated core morbid condition. And so what we expect for weight loss with intragastric balloons, and again, this is not meant to go to deep dive into bariatric endoscopy, but in general, we expect to see around a 10 to 13% total body weight loss in six months. But up to 12 to 22% of patients are non-responders at six months when we group kind of a bunch of studies together. And also when we remove the gastric balloon after six months, a weight recidivism occurs. And so you can see here in the graph that once the balloon was placed in red, you can see a sharp decline in the total body weight loss, but once removed at the six month mark, there is a slight weight recidivism that occurs. And so when do we start considering GLP-1? So this was a study done with the SPATS balloon that is FDA approved in the United States. All patients, 273 patients had the SPATS balloon implanted. And then the patients were offered loraglitide following the intragastric balloon removal. So 198 patients did not have loraglitide and the other 75 patients did. And what we see here is after balloon removal, we see that the weight regain is not as much when loraglitide is initiated. And so what we see is an additive benefit of loraglitide on the efficacy and then a reduction in body fat after IGB removal. So when do we consider in these specific patients who have had intragastric balloons? The one is that they don't achieve at least a 5% total body weight loss at one month after implantation. It's known that once you remove an intragastric balloon, then you can replace an intragastric balloon if patients have significant weight recidivism. And so if patients are not interested in repeat intragastric balloon therapy, then we can consider GLP-1 use. Or in order to reduce weight recidivism after balloon removal. The next one, the next bariatric endoscopy procedure that is very popular is the endoscopic sleeve gastroplasty. And these are full thickness sutures that are placed within the stomach in order to tubalize the stomach from 100% volume down to around 30% volume. And here what we see on the right is the data from the merit trial. And what we see is patients were randomized to diet and lifestyle in red versus in ESG in blue. And what we see is a significant percent total body weight loss of around 15% at one year. And once at one year, patients were allowed to cross over if they were in the diet and lifestyle group. And what we see is a significant reduction in weight as well. And so what happens if we start loraglitide in patients who have ESG? And so right now what we have for GLP-1 data that's actually published is the loraglitide data. And this is where a patient underwent ESG at time point zero and then they were able to start on loraglitide at five months post ESG. And what we see here is a significant increase in the total body weight loss when we have the additive benefit of loraglitide with an ESG. Now there was data published or data that was presented at DDW last year, looking at the same ethos but with semaglutide. And the results are quite remarkable where we started to hit over 20 to 25% total body weight loss with semaglutide but that data is not yet published. And so when do we consider GLP-1 versus when do we consider a redo ESG and how do we offer it into our patients? So a subset of patients will either have insufficient weight loss with an ESG or they will regain some weight after the ESG. And so this is a study that was published in 2023 looking at redoing an ESG. So in another endoscopic procedure, retightening everything with full thickness sutures versus initiation of medications. Of note though, that these medications that they were allowed to add at this point were older generation medications. So metformin, topiramate, topiramate and fentermine. But what we see here is when we combine pharmacotherapy with redo ESG, the patients who underwent a redo ESG on the second column here had a more profound percent total body weight loss than when initiating medications. Now that is in full disclosure that these are kind of older generation medications. This has not been done with a GLP-1 that's currently published yet. So we may see a more equivocation of this percent total body weight loss with the GLP-1 but the data to date does show significant benefit from a redo ESG in patients who have had insufficient weight loss or weight regain after ESG. And so again, when do we consider GLP-1 therapy in patients who have undergone ESG if there's insufficient weight loss or weight regain or if they're not interested in a redo ESG? Now, what about patients who have undergone bariatric surgery? And to date the most popular is the sleeve gastrectomy and the rheumatoid gastric bypass. But we know that in the last decades of bariatric surgery that there has been a efflux and influx of what is the most popular surgery at the time. Currently a significantly higher proportion of patients undergo sleeve gastrectomy. But in the 1990s and the 2000s rheumatoid gastric bypass was very popular. So remember 16 to 37% of patients may experience significant weight regain. And so in particular in patients who have undergone rheumatoid gastric bypass this is where we have the endoscopic option of a transoral outlet reduction or a TOR-E. And what you see here underneath is picture examples of this ESG TOR-E hybrid where ESG is done around the GJ outlet and then suturing is done in a purse string suture pattern around the GJ stoma and then significantly reduced over an eight millimeter or six millimeter balloon in order to really constitute what the initial surgical anatomy was which is a very small GJ stoma. So this is a paper that was done in 2023 looking at medication and TOR-E. And so what we see here in these patients, 145 patients is there was a significant weight loss from their initial rheumatoid gastric bypass but there was also a proportion of patients that had at least an average 20 kilo weight regain after their gastric bypass. And so here the study was looking at pharmacology TOR-E, farm therapy with TOR-E and then surgical revision. And what we see here is that when patients undergo pharmacological therapy with a TOR-E we start to get equivocal amounts of weight loss as compared to surgical revision. And remember surgical revision of a rheumatoid gastric bypass is quite a big revision where it includes limb lengthening therapy, et cetera. And so what we see here is using a less invasive endoscopic procedure when combined with additive benefits of pharmacotherapy really can start to equivocate weight loss outcomes with significantly less side effect or adverse events profile as seen here on the right. So the next goal is to see how do I manage adverse events when I see them when patients are on GLP-1 medication. And remember here we're just talking about at least GI specific adverse events because we are gastroenterologists. And so this was a random sample of 16 million patients from Farm Metrics Plus database. And so 4,000 of which were on loraglitide, 600 of which were on smaglitide, 600 of which were on bupropionol-trexone. And what we see with the GLP-1s is that there's an increased risk of pancreatitis, bowel obstruction, and gastroparesis. Now remember, not all patients will get this, not even a significant amount of patients will have these adverse events profiles, but this is something, the big three that we need to keep in mind. To a much smaller extent, some patients may get stone disease with significant weight loss, but by far the pancreatitis, bowel obstruction, and gastroparesis are adverse events of note. So the first way to handle this is proactive counseling of side effects. So we need to tell patients that most side effects are mild to moderate. Nausea typically subsides after dose escalation is done. So after a month, so if we take smaglitide, for example, we start at 0.25 milligrams. After a month, we increase to 0.5 milligrams. What we can tell patients is within the first couple of days after dose escalation, this is when the nausea is typically at its worst and can typically subside. There are behavioral aspects to reduce nausea, including small meal sizes and mindfulness to eat before feeling full, decreasing in high fat foods, spicy foods, or carbonated foods, especially during dose escalation. And we wanna address any issues with bowel movements prior to initiation. So if they're constipated prior to starting a GLP-1, we wanna make sure that we have that under control before initiating a GLP-1. So for management of short-term or mild side effects. So nausea by far is very predominant. In patients who are older, it is recommended that to reach for Domperidone over Reglan given the concern for tardive dyskinesias with Reglan in older patients. This occurs around 15 to 50%. The nausea occurs around 15 to 50% of patients. And again, it's of the highest prevalence within the first couple of weeks of dose escalation or dose initiation. Next, some patients may get diarrhea. And so this is when starting a probiotic and or antidiarrheals is very helpful. And this typically decreases after four weeks of GLP-1 use. Some patients ever get constipated. And so we need to increase the fiber and water intake and initiate stool softeners like Docuthate or Colace when initiating GLP-1s for these patients. And again, the mean duration here is around 47 days on average when we see constipation. Now, if the symptoms worsen, you can reduce the dose. So if patients are not handling the 0.5 milligram dose, then we can reduce down to the 0.25 milligram dose, but we need to counsel patients of at what dosage in the trials did we actually start to see significant weight loss? And again, there was some weight loss seen at the lower doses of 0.25, 0.5 milligrams for some at the time, but really the significant weight loss was at the one and 2.4 milligram doses. So that needs to be counseled if patients cannot handle a higher dosage because of side effect profile. We also need to manage expectations that we typically saw within the trial. This is a good paper that I saw in order to print out for patients and how to adjust their eating habits. You wanna eat slowly, smaller portions. This is a good way for patients to understand what to expect to do when starting a GLP-1. You want a low-fat diet, you want more clear drinks, water-rich foods. Again, you want some exercise, a food diary while initiating the medications to see what kind of are triggering events and what makes the nausea or bowel movement changes worse. For nausea, eating crackers or drinks after GLP-1 may help, avoiding strong smells. Again, these are the things that we can show patients for vomiting, for diarrhea, for constipation that are easy for patients to understand and to expect how to manage. Next is what about if we have persistent or severe GI symptoms? So if patients have persistent symptoms, even on low dosage or severe GI symptoms like pancreatitis, bowel obstruction, gallstones, or gastroparesis, you wanna pause that dose escalation first. Now, not everything is related to GLP-1 use. People can get nausea for other reasons other than the GLP-1. So we wanna make sure that we think of all possible diagnoses beyond just the GLP-1 that could be causing, again, these are very common GI disease processes, even independent of the GLP-1. It's very important to maintain hydration given that nausea and delayed gastric emptying are big side effects that patients can experience, and a dose adjustment. So you can, again, lower the dosage if you're unable to tolerate a certain maintenance dose. And if patients are symptoms-free at a lower dose, you can try the increased dose again if needed, but if they can't do that and they were able to tolerate, say, a GLP-1, but at some point they had significant nausea and vomiting at, say, one milligram, and you came down at 2.5, but they're still not losing weight. If the low dose intolerance, you can also switch to another GLP-1 if it's clinically indicated. Again, switching to another GLP-1 is not validated in patients who, say, have bowel obstruction, severe delayed gastric emptying, or pancreatitis. This is for persistent symptoms. They have nausea, vomiting, or changes in bowel habits that are really seen when the dose is escalated. Those are still able to switch, you are still able then to switch between classes if these are not severe GI side effects symptoms. You wanna, again, hold the GLP-1s for the severe GI side effects. The really unclear thing here that we need more studies on are patients who have asymptomatic pancreas enzyme elevations. Currently, the ethos is to stop the medications, and there's a little conservative thinking as to not switch them to another GLP-1, but these are a subset of patients that we really need to study to understand are these clinically relevant elevations, would they have been clinically relevant elevations if they were continued on their GLP-1, and is it safe to switch if they have asymptomatic pancreas enzyme elevation? Again, this is a really good handout, again, from the same paper of how to dose escalate patients or how to dose escalate or deescalate when patients can only maintain a certain dosage on a maintenance phase, and then what to do when patients have nausea, vomiting, diarrhea, and constipation. For a gastroenterologist in particular, so I put this as a three A's, how do I manage GLP-1 medications in the perioperative setting? And the concern here is the risk for retained food contents and endoscopy in patients who are undergoing these medications. Now, the American Society of Anesthesiologists recommends kind of holding all medications prior to the procedure for varying days based on whether it's a subcutaneous or an oral medication that they're taking, and in general, GI societies, whether through multiple CPUs have recommended against universal holding, the recommendation of universal holding unless patients have symptoms or other considerations like diabetes status. Now, the important thing to understand here is the consideration that 1-tachyphylaxis can occur, meaning that in certain patients that the retardation of gastric emptying that happens while on GLP-1s can actually reverse. And so in studies, it's been shown that for loraglitide after around five to 16 weeks of being on loraglitide, that patients that may have had profound gastric emptying before actually did not have that bout of gastric emptying after a certain amount of time while on the GLP-1. And this is thought to be driven more by a response of the vagal nerve function rather than kind of GLP-1 receptor downregulation or desensitization because of the weeks on medication before we see these effects. Again, tachyphylaxis, meaning not as a significant delay in gastric emptying, occurs more in long-acting GLP-1 medications, and it occurs in more long-term use of short-acting GLP-1s. And so this is something to keep in mind that we're actually seeing this tachyphylaxis phenomenon that happens, and that some patients may not have such profound delayed gastric emptying for so long of a time. And so the only thing that we have published so far is the effect of GLP-1s on colonoscopy prep. And what we saw was slightly poorer prep when patients were on GLP-1s, and the percent of patients and the adverse events rates were quite similar. So innately, what we have is an absence of quality publishing data on GLP-1s in the perioperative setting. Influx of data is coming, we know that. In order to be able to understand kind of baseline characteristics, the utility of kind of perioperative gastric ultrasound as well as risk stratification based on patient characteristics. And then there will be consensus exhibit or opinions coming on this matter. So stay tuned on this, because I know this affects our daily lives and our endoscopy units as well. So with that, we covered the three goals of the second part of this presentation. And so we'll stop here, and we will all gladly answer your questions. So again, special appreciation to the ASGE and the ABE for sponsoring this very important webinar, and it's been a pleasure to be able to talk on this topic today. Awesome. All right, well, thanks everyone. What a great overview from Dr. Narang and Dr. Khan. We went through all of basically the incursions that we use, their mechanism of action, and essentially how one approach is not, one size does not fit all for all of our patients, and that we really need to find unique, multidisciplinary approaches to treating these patients. So we have a lot of questions, and specifically for Dr. Narang and Dr. Khan. So I'm going to start with the first question from the audience. So thank you for the great presentation. So what should be the approach in patients on GLP-1 agonists who present with acute pancreatitis and also have cholecystis on imaging? Great question. So I think this is where it comes to, these are very common GI issues that we see as well, and it's very tricky. So I think in general, in general, we would consider holding the GLP-1, but unfortunately, we're kind of in this, then is it the chicken or the egg? Which one actually contributed to the pancreatitis? And unfortunately, we just don't have enough data yet to say it is safe to continue a GLP-1, assuming that it's cholecystis, unfortunately. And so again, this field is primed for more research in this area, but at this time, I would hold the GLP-1. Yeah, I found some people, actually, when they're going through weight loss options with patients, like they'll have like a pre-intervention ultrasound and they'll kind of restratify them based on that, assuming that they're gonna lose weight. And we know that patients who lose weight tend to also develop more stones in their gallbladder. So that's something to just always counsel them on. But thank you, Dr. Phan. So our next question is, what is your suggested strategy for anti-obesity medication or special care with GOP1 agonist in obesity patients with depression or major depressive disorder? I can take that one. So, you know, it's really important to have a comprehensive approach to weight management. And so, I mean, we've been using these agents for diabetes management for almost 20 years. The first GLP-1 agonist was introduced in 2005, Exenatide, which was Bietta, twice a day for management of blood sugars. And so, I mean, only in the last two years or so has a lot of this come out about depression and suicidality. And while I think it's really, really important to assess that, you know, we don't know what, again, like it's like chicken or the egg, right? And so that's exactly why it's really important to make sure that we have a comprehensive approach to weight management. It's really important to make sure to get patients in with a psychologist and, you know, make sure that they're addressing these issues before potentially starting treatment. And I think if it is severe depression, then I would give it pause, right? Like for Terzapatide, for example, for Zepfound now for, you know, for FDA approved for weight management, this is now part of, you know, like safety data where if someone has suicidality and severe depression, you might wanna, you know, take a second look as to whether this might be the right fit for that patient. And of course, if that develops while on the medication, then I would recommend stopping it, but I would 100% if someone has a history of depression, please have them assessed by therapist or psychiatrist first prior to starting any agents. And I think a comprehensive practice usually will employ, you know, whether it's like the psychologist already, you know, et cetera, to evaluate the patient. Thank you so much. Okay, so I have a bunch of other questions for y'all. And this question specifically for both of you, as you're doing your weight loss consultations with these patients who are walking into your door, they're hearing all these, you know, things about GLPs, but they're also hearing about bariatric endoscopy and basically surgery as well. So, you know, what is your general approach when a patient walks in through your door and asks, you know, should they start medications first or should they undergo an endoscopic weight loss procedure? Or are you sitting there saying, you know, we kind of have to, you know, have an individual approach to this and depending on their desired goals. So, I mean, what is your, both of your approaches to a patient like this? From my end, I don't do procedures. So I would 100% look at the lifestyle portion of it and potentially consider weight management. Typically, I almost, you know, do a stair-step approach. And, you know, with lifestyle alone, if it's, again, every patient is so different. So if someone is, you know, I don't wanna make too many exaggerations here, but let's say if someone eats fast food every single day, well, no amount of GLP-1 is gonna fix that until they fix, you know, the way that they're eating, for example, or, you know, the way that they're approaching their dietary pattern. Same thing, like, you know, if they're not necessarily improving as much on medical weight loss therapy, that's when we start to consider procedural therapy. And I'll let you take it from here. Yeah, I think it's really important that obesity is very different from kind of other disease processes that we're typically used to, especially from procedural standpoint. So when they come into my clinic, my clinic is not just the procedural standpoint, it's with my surgeon and my clinical medicine cohort, right? So we're all together to make sure that there is a big market and there is a big need for GLP-1. But there are, again, patients who will not respond or may need both. So for, I'll give you an example. So I have a patient who BMI of 50 that needs a hip repair because she has, because she can't move, right? She can't, they don't wanna do surgery because she has a big hernia. So she needs to lose around 30% body weight. This is not achievable to a degree with ESG alone. I'm a big fan of it, but this is where together in combination with my clinical medicine physician, we'll initiate her together with an AOM and an ESG in order to get her to this weight loss goal because there's a specific endpoint. And so each patient is very different. And when we're doing kind of a bariatric endoscopy practice, I think most of us cannot stress that it has to be in combination with our surgeons and with our medicine colleagues and endocrinologists to really give this holistic care to individual patients. Awesome, thank you so much. So, you know, say, so Dr. Naran, say like someone comes in to your office and, you know, they've been on these incontinence medications, you started them and they're doing great. And now they've reached their target goal. Do you stop it? Do you down titrate those medications? What do you do? How do you set those expectations with them so they can still have the benefit and success of losing the weight on the medication? Where do you, you know, what's your approach to that? Yeah, this is, you know, such a popular question with this because I think there's a lot of, you know, perception that, oh, you know, I'll just take this for a few months, get back, get to my desired weight, and then, you know, we're good to go. And unfortunately, that doesn't work that way. And so, you know, when we spoke about the physiology of weight gain and loss, what these medications are doing is that they're suppressing the hunger hormone. And so if we take off the medication, well, here goes the hunger hormone, and it goes all the way up, and people's hunger often returns. And if we look at the SIRMEL-4 data with terzepatide, you know, you saw this curve where people who were on terzepatide at 36 weeks had lost, you know, a significant amount of weight, and then they were split into placebo versus the terzepatide treatment group. Well, the placebo group, off of the terzepatide regained most of that weight. And so there are studies currently ongoing to determine if one of these agents is going to allow for either weight maintenance or, you know, prevention of weight regain, concrete data, except for that terzepatide study right now. And so part of it is also setting expectations, but again, like, let's say someone's been dealing with obesity for the last 30 years. Well, treating you for a year or two on a patient isn't gonna fix the last 30 years. This is a chronic disease. And, you know, we don't bat an eye to taking medication for hypertension or hyperlipidemia or diabetes long-term. This is the same thing. And if we do, we're not gonna necessarily have as many issues long-term with cardiovascular risks like hypertension, hyperlipidemia, et cetera. So I look at this as a long-term agent, and we don't have data right now about down titration, at least not that much. Yeah, I think there's a, you know, there's still a lot more to be studied and learned about for these medications and how we're supposed to kind of incorporate them into kind of even our endobariotic practice. But, you know, Dr. Phan, so, you know, when you're performing ESGs or TAURIs or on these patients, are you starting anti-obesity medications on all of these patients? Are you starting them at the same time? What's your, what's kind of like your protocol? Do you start them one month after or six months? I think there's like a lot of different approaches, but what do you, you know, what's your approach to that? So I think a lot of patients come to a bariatric endoscopy practice in varying parts of their therapy so far, right? So I would say a good proportion of my patients are actually on an AOM, and they haven't achieved the weight loss that they want, and then we want to start ESG. So typically when I have a patient that's already on a GLP-1 and an ESG, I'll get them to their achieved target weight, which is at the six-month, nine-month mark, and I'll actually start to try to down-trait, down-titrate their GLP-1 one step at a time, super slowly. Do we have data for this yet? No, do we have studies that are looking at this? Yes, but you know, this is what I do in my practice, because I think, you know, the ESG really kind of may help you sustain some of that weight loss, just like really intense exercise may help you sustain some of that weight regain that will happen with your AOM. But if patients, again, some of my patients need to lose a significant amount of weight, say for transplant purposes, and surgery is not an option, and again, I think surgery is a fantastic option, but if they're not gonna get there, or they can't get surgery, then I do start them at the same time. I want to get them to their goals quickly at six months in order to get to a secondary endpoint, and I'll do, I'll start them together when there's a clinical endpoint that I need to meet for some reason, some sort of surgery, some sort of transplant, something like that, that I really need to get them there at six months to 12 months. Awesome, I love that. So, you know, on the topic of GLP-1s and endoscopy and doing these procedures, you know, there's been a lot of talk in the last six to eight months about, you know, the timing of stopping these medications before endoscopy, and there is a discord between the GI societies and the American Study of Anesthesiology, and, you know, I think, you know, the AJA did come out with their own statement, their clinical practice update stating that, you know, patients were taking GLPs solely for weight loss and can be identified beforehand, and adjusted medication could be withheld before endoscopy with likely little harm, but again, like, you know, how are we approaching these conversations with patients and also our anesthesiology colleagues, especially since now there's, you know, a lot of our patients are on these medications. Oh, sorry, it's up to me. Um, so it's true, so I think, you know, I think within the next year, we're gonna see a lot of data coming out about what we do with these medications and for upper endoscopies and colonoscopies in particular. I do first want to address kind of a question that is kind of similar to this by, I think, Dr. Bardwaj, that said, are there any specific colon preps that we should consider with GLP-1s? So, for GLP-1s, what we should consider with GLP-1s? So, for that in particular, we don't know, right? There's already kind of controversy as in clear liquid diet versus low residue diet with kind of weak data, but suggesting that low residue diet is equivalent in terms of being able to see everything and kind of similar ADRs as clear liquid diet, but we don't know this specifically in patients with GLP-1. And so, again, I think this has, this, if anything, can spawn more research in order to understand what we do specifically on these patients. But I would say that, you know, data is, it will be coming out that the type of GLP-1, how long we were on GLP-1, how long that it's held may not be as important as their underlying diabetic status. And that may be kind of a big driving force for if patients are going to have delayed gastric emptying, that's clinically meaningful. And I think that we're going to see that, you know, the delayed gastric emptying, it's important, but it may be overplayed kind of in the universal setting of clinically relevant, you know, amounts of retained food, aspiration events, things like that. Those are all important, but it's within what we typically see for patients with diabetic gastroparesis, but we don't hold everything. And from my standpoint, if a patient comes to me asking, you know, when they should hold their GLP-1 prior to, you know, a GI procedure or any other procedure, like in the last, gosh, decade, aside from the last year of a lot of hoopla around this, I've just held it a week before. And let's say if their procedure's on Wednesday and their last dose was last Wednesday, I'd still have them take that. It's more within that five-day range than I would say, okay, take it after your procedure. So from like a clinical standpoint or anecdotal standpoint, I've found that that's honestly worked fine and I haven't had any issues, you know, happen after that. Yeah, I do presume that it's probably going to be some sort of a stratification and some like algorithm that we're going to end up putting these patients in just to kind of figure out the timing of this. But thank you so much for both of you for answering that question. So we have another question. So for choosing anti-obesity medications to combine with bariatric endoscopy, is there any particular group of patients you would suggest other anti-obesity medications apart from GLP-1 agonists? So we're looking at medications like fentamine, Contrave, things like that. What is your general approach? Yeah, so I think- No, sorry, I use fentamine and Kissimmee a lot. And so given like the national shortages that we've had, we've had to sort of like get creative with this. And so I clinically don't see too much weight success with Contrave, but often like a combination of fentamine and topiramate, it might help take the edge off a little bit, but it's certainly not to the degree, well. So I completely agree. So I think Kissimmee and Contrave really got, I think in some patients who undergo a bariatric endoscopy procedure, they feel full quickly, but they still have this like urge to eat. And I think fentamine is really good, again, as a short-term agent to kind of help them through that initial time after doing like an ESG or a balloon therapy. And so that's where I'll kind of reach for fentamine, again, as a short-acting agent, less than 12 weeks, as they're starting to get these cravings under control. But I agree with you. I think Kissimmee and Contrave, we've had to use them with insurance issues as well as national shortages. And I think what we don't know is what happens to patients when we start GLP-1s, come off GLP-1s, start GLP-1s, come off GLP-1s, how that affects underlying metabolism as well as ability to achieve a goal weight loss. And I will say for fentamine, I often don't use the highest dose. I'll usually do La Myra, eight milligrams, and have patients start with four milligrams, like a half tablet, you know, just to kind of get them started. And so I actually never use full fentamine for patients. That's awesome. All right, so let's see if we have other questions. Okay. That sounds like a good one. Do you mind if we actually, maybe, yeah, let's ask the IBD question and then the poorly diabetes with gastroparesis question. I think that's a really good clinically relevant one. Yeah. Okay, so as these drugs might confer benefits on non-metabolic disorders, do you recommend GLP-1 receptor agonists as an adjunct in the arsenal of drugs against IBD, specifically in patients with obesity? I don't know if you can go ahead. Oh, so, you know, from an IBD standpoint, I usually will be okay starting patients on GLP-1s as long as their symptoms are in control. So obviously in the middle of the flare, or if they don't have necessarily controlled IBD, I won't start it. But if, you know, if their disease is stable and they're doing well, and they're dealing with weight gain, I think patients have done quite well on GLP-1s. I'm not sure what your experience is. Obviously, you see a lot more than I do. I think I agree. I mean, we know that IBD also confers cardiovascular risk and with kind of these newer agents and having that, you know, 20% MACE data is really important. Again, having a flare or having inconsistent bowel movements or an elevated inflammatory markers, you would probably hold off until there's quite a bit of stability. So in my mind, when I started GLP-1s, I want at least six months of stability of something, right? Kind of bowel movements are really good. Same goes for IBD being pretty well controlled, right? I think six months is a, you know, it's a shoot in the dark timeline that I use, but I think it at least confers enough chronicity where the risk benefit ratio tends to lean more towards safety, I think at this point, but we just don't have the data in general. We just don't have the data yet, but I think time is important. Definitely. So just to move along, another question, can you start GLP-1 in patients with poorly controlled type 2 diabetes and possibly gastroparesis to control diabetes? Yeah, I would rule out the gastroparesis diagnosis first. And so, you know, I think that's where, you know, some of the propaganda around gastroparesis suddenly being a long-term side effect of these medications has come about. And I think it's because people aren't being screened appropriately. And again, we've had 20 years almost of use in the diabetic population of these agents, and it's only sort of come to light in the last year or two, you know, with this whole gastroparesis occurrence. And so those patients should not be good candidates, you know, for GLP-1. The other is that if otherwise things are well controlled, you know, their gastric emptying study looks okay, you know, it may be a mild disease, then they may be okay. Worst thing is they try it, they feel bad for a few days, heaven forbid, and then you stop the medication. So it's not something that will cause permanent effects, not that I love to do something like that, but, you know, even in our population without any gastroparesis history, if they don't feel good on it, we stop. And so at the end of the day, it is elective medication, but I do think it's important if they have symptoms of gastroparesis that we rule that out first, and then think about starting it. Yeah, okay. I don't know, are we going over time? Do we still have some more time for other questions? I'll take that as a yes. Okay, so we can go all night and talk about this, guys. Like, there's so much to talk about. So do interruptions of GLP-1 decrease metabolism, or increase the likelihood of resistance of the medication? Now, this is an interesting question. The plateau effect, I think that's what this person is referring to. I think different people respond in different ways. And I think we've seen it a lot during these shortages where people may have been doing really well, for example, on Wagovi, and then, you know, of course, they couldn't get refills of their medication. And so I've seen, unfortunately, patients regain a lot of the weight that they initially lost and had a lot of success with. And then restarting it has been a bit of a rocky road as well, right? Because again, like the shortages and all of that. And so some people do fine when they get back on and, you know, restart like a consistent lifestyle, and others may not respond as well. And there are ongoing studies, again, looking at hyper and hypo responders, but this on-off, on-off is really prohibitive to, you know, success with long-term therapy. Yeah. Agreed. I'm just told I can go as long as I want. So that'd be great. All right. So just respecting everyone's time. So let's see what else we have here. Is there a specific combination of DOP-1 agonist and endoscopic procedure that you prefer in patients who need significant weight loss in a short period of time for surgery and or transplant? Like, are you focusing more on one type of increment versus another? I think some of it, the easy answer is going to be supply and what the insurance is going to cover. But in general, again, I want to think that ESG is going to achieve around, say, conservatively 12%, national 15% around the six-month mark, right? So if I need to achieve only 20% to 25%, Smaglutide is really good. Laraglitide is really good for that. Again, it's what my goal clinical need is. So for my patient that needs 20%, 25% as quickly as possible for surgery, then maybe I'll try to go for Terzapatide just to get an enhanced kind of response. But you don't want to do that on every patient because not every patient needs that. And so it really is what is our end goal. Yeah. All right. So I'll put out one more question, and then I think we'll conclude the webinar. Thank you both for answering all these questions. So do we know of any other ESG devices in development besides EndoMina and OverStitch that are expected to achieve higher weight loss? So I think Rabindra Watson, who I think is on here, suggests EndoZip is another one that is coming up. You know, not all of these have more exaggerated weight loss results, but significantly higher than ESG currently. I think, you know, there's robotic systems coming out. There's magnetic systems that are coming out. So we're in a big kind of boom of devices that are coming out here. And as we start to combine these with medical therapy, we really are starting to get to kind of surgical weight loss levels. So I would say in the next five years, I'm sure that more devices are going to come out. And we may actually be more sustained, but also we'll have great results. But again, so far, the ESG is kind of the most commonly used. Yeah. Well, thanks again for everyone for joining. And Dr. Narang, Dr. Phan, you guys are awesome. And obviously, if you guys have any further questions, feel free to email any of the leadership, ASGE, ABE. And hopefully, we can talk about it during our next one. Thank you. Thank you. Thanks for having us.

obesity

GLP-1 agonists

weight management

diabetes control

semaglutide

terzepatide

lifestyle changes

bariatric endoscopy procedures

intragastric balloons

sleeve gastrectomy