My name is Reshmi Srinath endocrinologist from the School of Medicine at Mount Sinai in New York I'm here to present the first part of today's annual year in review talking about obesity and nutrition So first no disclosures today or financial conflicts of interest I'd like to recap a little bit last year. Dr. Agarwal actually gave a wonderful year in view talk and Some of the themes that emerged were one we really were impacted by COVID We talked about the impact of acute illness how this contributed to undernutrition and also the role of obesity how obesity actually contributed to greater Complications particularly looking at risk of ventilatory support mortality cardio metabolic Outcomes so again a lot of focus on COVID in the pandemic There was also discussion of the dietary guidelines that were brought out from 2020 to 2025 And these really emphasize the role of limiting processed food intake Focusing on plant-based diets and the idea of an 85-15 role and rule This again suggesting that 85% of your calorie should be taken in for the appropriate food groups and the other 15% to be used for other uses so sort of for you to to play with Other themes of last year's talk we talked about plant-based diets their role in cardio metabolic and mortality and the role of fruit and vegetable intake Today here are some of the themes that I will be discussing so first talking about again obesity in a pandemic how it's impacted all Of us to the growing role of telehealth how this has really contributed to our ability to improve obesity care Three talking about screening and the role of specific dietary patterns And lastly some updates in endobariatrics and legislation So a lot of studies have been done in outside populations outside the u.s. Really looking at the changes in eating behavior This was a study released in early 2022 Looking at intake of sugar-sweetened excuse me desserts and sugar-sweetened beverages We know that kovat 19 has created a lot of disruption in our lives both work school businesses And this was a study where they utilized a survey that was released in the spring and summer of 2020 So this is early on this was done in adults over the age of 18 It was utilizing an online market research panel, and they captured an n of three thousand nine hundred and sixteen adults Their outcomes were looking at the consumption of unhealthy snacks and desserts and sugar-sweetened beverages And these are some general results which I've sort of listed out here But as you can see majority of them did indicate they were in eating Somewhat more unhealthy and drinking more sugar-sweetened beverages as you can see really and I'll present the data in the next slide That younger adults those were lower income and Particularly racial and ethnic minorities had greater intake of these unhealthy snacks and beverages, so this is really crucial for how we approach care And limitations obviously this is a cross-sectional study, and it was utilizing a survey So here I sort of highlight I don't know if I have a pointer But um you can see sort of highlighted in red so they use the reference group of over 65 And what we can see here is that again all of the younger age spans had greater intake of unhealthy snacks and desserts They also use males as a reference and they found that females had some greater intake When you look at race and ethnicity we can see that black non-hispanics Had greater intake of unhealthy foods and looking at income annual income under 35,000 was associated with greater intake and they used a reference of having a Income of over a hundred thousand as their reference there In terms of sugar-sweetened beverages again looking at the younger age groups having greater intake of sugar-sweetened beverages We know again looking at racial minorities and in different ethnicities Comparing those to the white non-hispanics had greater intake and also here you can see some influence on Education so those who had lower education had greater intake of sugar-sweetened beverages And again the income So I think the key points here are that many of us changed our eating patterns during the pandemic and it predominantly affected certain Populations here within the US again taking into account. This was a survey. It was very early on But it did capture some important data I'm gonna shift now towards looking at telehealth So a lot of us now are doing both in-person and end video visits or e-consults or any form of telehealth This is actually a study done Presented in obesity. It was retrospective. So it was done Utilizing a comparison group So those who were taken pre COVID and those who were establishing care during COVID and I should clarify the early part of the pandemic Here there was an end of 245 and they utilized three groups so they had those who were completing in-person visits only those who had a hybrid of both in-person and Telehealth visits and those who were purely video visits and you can see here in table one So average median age was around in the mid low. I should say mid 50s or 49 or so majority of them were female Average weight was around with a BMI of around 35 Again, predominantly Caucasian or white and many of them actually had been on metformin prior to establishing care Here we can see their weight loss outcomes So across the board again comparing our three cohorts in-person hybrid and video there actually was really no significant Difference across the three groups So this seems to suggest and again the top chart shows greater than 5% weight loss and then greater than 10% weight loss And again, there is no significant differences across the three groups And what that seems to suggest is that maybe you know, we know that majority of us were more sedentary with the pandemic But maybe we were more focused on weight loss when the pandemic started it's hard to say this is really gonna need more Interpretation more further studies, but I think it brings about the idea that you know, really having good care is is really important This is another study again looking at the idea of telehealth and looking at a behavioral intervention pre and post COVID This is also done in adults BMI 28 to 40 and here they had three cohorts. The first one was pre-COVID pandemic 2018-2019 The second cohort was 2019 to late December 2019 and the third cohort was basically 2020 So early onset through mid pandemic And this was a behavioral intervention where they had a 12-week acute intervention where they were using weekly Group visits with an RD and then they had a maintenance phase of 27 weeks where they had monthly visits in addition Subjects were encouraged to follow a calorie-restricted diet. They were encouraged to engage in moderate physical activity at least 150 minutes per week and they were both supported through telemessaging and video and these weekly or monthly visits This is table one and again, I'll emphasize what I've sort of pointed out with the arrows again predominantly female in their population Average BMI was around 34 and again predominantly Caucasian I think this is sort of a theme in many of the studies that We seem to be capturing more females and males in majority of these studies But what I can show you is that on the left we have sort of a graph of all the participants Looking at weight change and in black is highlighted those who were seen in the COVID cohorts and in Or I should say whitish gray are those who are seen pre-COVID and interestingly The patients who were seen in the COVID cohort actually had greater weight loss So at week 12, which was the acute phase of this behavioral intervention The pre-COVID cohort had only lost 3.87. That should be kilograms not milligrams And versus the COVID cohort had lost around 8.79 kilograms After that maintenance phase again, the COVID cohort maintained greater weight loss So this is also demonstrated on in the graph on the right so you can see sort of that downward trend that continued Over the 12 weeks of that initial acute phase of this intervention Oops What I wanted to point out here also is that this points to this idea that there was potentially greater adherence greater interest greater Motivation in those patients who are seeking care during the early onset of the COVID pandemic and we should also mention that there was really no difference noted in physical activity, but Patients who were seen during COVID had I should say during the early part of the pandemic did report greater sedentary time That data was not fully captured, but it is something to take note of Next I'm going to sort of jump to screening and I know this is a bit of a whirlwind But this is a sort of a study looking again talking about BMI cutoffs We know that Asians, South Asians, other ethnicities have greater risk of obesity cardio metabolic disease at different BMI cutoffs So while we use a BMI of 30 or higher to define obesity We know that this number can be different in other populations This was a study using electronic medical records in primary care clinics in England They captured an N of 1,472,819 adults These were healthy individuals without diabetes and what they were looking at was the outcome was incident type 2 diabetes Over approximately six to seven years of follow-up They chose this really again knowing that we look at a threshold of BMI of 30 and trying to capture this outcome interestingly over time approximately 6.6% of the total population developed diabetes And that's important to note because that may be different from a US population or a different population from a different country And what's presented here in this graph is the appropriate BMI thresholds, so this was a multi-generational study across multiple different ethnicities And what they found was that using a threshold BMI over 30 in Caucasians They found that a BMI of 23.9 in South Asians, a BMI of 28.1 in blacks, 26.9 in Chinese, and 26.6 in Arab populations So again reinforcing this idea that BMI thresholds are different in non-Caucasian populations and Increasing our role and really focusing in addressing obesity outcomes I'm gonna jump now to another huge study that just came out in the last few months. This was in the New England Journal Talking about the role of intermittent fasting so many of us cancel our patients They're following caloric restriction, and they ask us what about this thing called intermittent fasting does it work is it effective can I do it? So this is a study done And it looked at 139 healthy individuals BMI 20 to 40 and these were randomized to either intermittent fasting with caloric restriction or Just intermittent fasting or what we call time restriction for 12 months those who are on the calorie restricted component did restrict their calories to 1200 to 1500 calories per day for women and Approximately 1500 to 1800 calories, and you can see sort of the spread of their calorie intake over time And it's important to note the time interval that they used this was from 8 a.m.. To 1600 which is 4 p.m. So again, that's that's really key in this study And what they found and this is demonstrated in the table up and and the graph here is that there really was no significant Difference in weight over 12 months between the two groups as you can see In the bottom actually that illustrates really the the key is those who lost more than 5% more than 10% and more than 15% Really no significant difference There was no significant difference in body fat mass Lean mass visceral fat or subcutaneous fat and this was obtained with body composition Excuse me with dexa They also looked at blood glucose insulin and home IR and lipids and they found no change so again reinforcing this idea Or at least the importance of intermittent fasting is it really? The key is by itself, or do you need to combine this with a caloric restriction? I think this really points to the fact that you need you need both But what they do note is that again. This was a population who was relatively healthy. They didn't have diabetes They didn't have heart disease so this may not reflect our population that we're seeing They were also restricted as I said to really this Tight window most of us are still working at 4 o'clock in the afternoon So to stop eating at 4 o'clock we would have this huge window of time in the evening where we wouldn't be able to eat So that really it's hard to apply to some some of us They did not capture any data on physical activity so that really can affect us as we know just hearing from the wonderful lecture earlier That physical activity can affect energy expenditure and and can impact their weight loss outcomes And we have no data on energy expenditure so could their energy expenditure have shifted over time with these various diets That's possible, and we just don't know so I think this is a key study Obviously was published in New England Journal, but I think more data and more studies are needed combining not just the diet But looking at physical activity looking energy expenditure capturing body composition and capturing these metabolic outcomes And seeing how beneficial they are This is another study looking again looking at diets, so this was using the look-ahead trial Again, we know that some of us say breakfast is good for you Some of us say it's okay to skip breakfast many of our patients want to do want to do whatever we tell them to do And so this was a study looking at Utilizing look-ahead study where as many of us know this was over 3,000 subjects who are randomized to an intensive lifestyle intervention Versus standard diabetes care and that intensive lifestyle intervention included targeting 1,200 to 1,800 calories a day engaging in at least 175 minutes of moderate physical activity per week and Targeting a weight-loss goal of 7% or more and what they looked at was breakfast consumption and their weight-loss outcomes So what they found was that eating breakfast was associated with greater weight loss over four years And what you can see here is on the left is the standard group and on the right is intensive lifestyle intervention and those highlighted in Darkish black are those who were never or occasionally eating breakfast those in the middle and the gray are those who were Most days of the week eating breakfast and those in the right who are eating breakfast every day And as you can see that those on the right who are eating breakfast every day clearly had greater Significant change in weight as well as weight loss and they also had a significant change in weight As well as weight loss outcomes in the intensive lifestyle group versus in the standard group. There was really no significant change The question was what is mediating this difference and so they then looked at physical activity and they found that across the group that physical activity actually was Increased in those who were doing this intensive lifestyle intervention. So here on the left you have the entire cohort So again looking at never or occasionally eating breakfast most days eating breakfast or every day eating breakfast as you can see Those who were every day eating breakfast definitely engaged in more physical activity And then looking at year four Over the entire study again, those randomized to intensive lifestyle intervention were engaging more physical activity so the question is whether that impacted the outcomes in the look ahead study and Affected their weight loss. So again utilizing this idea that both food intake matters, but exercise plays a role as well Similarly on another span of looking at diets a lot of last year we were focused on plant-based diets mediterranean diets and this was a study looking at the mediterranean diet and Thinking about what else can the mediterranean diet do? We know it affects us both in terms of cardiometabolic outcomes affecting potentially mortality cardiovascular outcomes But can it also play a role in mental health? This was a study earlier presented this year in nutrients So they looked at the NHANES study they captured over 11,000 Participants and they captured a 24-hour diet recall where they assessed their adherence to a mediterranean diet pattern And this was using an alternate mediterranean diet score Which was a point scale from 0 to 9 then they looked at depression and this was using the PHQ-9 Which is scoring them from 0 to 27 points. Their population was approximately 50-50 female average age about 46 predominantly white or caucasian And what's key to note here is that so quartile 3 and quartile 4 highlighted in red are those who are More adherent to a mediterranean diet and what they found was that those who are more adherent to a mediterranean diet had Approximately 40% lower odds of depression. So the data's presented a little bit backwards They're saying you know 0.6 or 60% greater odds of depression. You can also say Lower odds of depression with greater adherence What they also know is they then looked at controlling for lifestyle factors So they looked at smoking their physical activity their alcohol use and they found that this Significance actually was attenuated by some of these lifestyle behaviors. So again the idea that Mediterranean diets not only can improve cardiometabolic health, but potentially Potentially can be associated with lower risk of depression. So a key a key factor there I'm gonna jump now again to another topic. So I know we're having a lecture on Endo bariatrics later in this conference, but I wanted to just mention briefly as this is a year in review that One was this removal of I should say withdrawal of the aspirin cysts So for many of us this was a procedure done Endoscopically where there is a catheter insert into the abdomen and where patients were instructed 20 to 30 minutes after a meal to Open the catheter, you know To basically remove or expel the food contents and this was to be done every meal And early February of this year Aspire bariatrics actually withdrew their product And so I think this is a key point to note and I'm not gonna talk more about endo bariatrics So I know there's a great lecture coming up later this weekend. I Also just want to hint about nutrition and legislation so Every ten years or so the FDA and and legislation talk about nutrition and so coming up this year, there is a child nutrition reauthorization, so this is a Key legislation that looks at nutrition programs. So this is affecting school lunches This is affecting the breakfasts that are being served in public schools Food services. This is affecting WIC as well as fresh fruit and vegetables and farm-to-school grants So this is something that's going to potentially be discussed and hopefully have some positive outcomes later this year But I wanted to mention this as well And as many of us are familiar with the Treat and Reduce Obesity Act This was brought up last year again introduced into the Congress of the hundred and seventeenth Congress in March I was curious to see what were the outcomes. It sounds like it was passed on to the subcommittee on health I'm not aware of any further Input or any further discussion, but this is something that many of us are very partial to and really it's going to impact not only how we treat how we Appropriately screen patients for obesity and it's going to affect the The coverage for intensive behavioral therapy and we can potentially utilize not just physicians but nutritionists and other Types of health care workers. So I bring this up just because it's a key point of legislation Last but not least. I just want to mention World Obesity Day. So this came up in March earlier this year Again across the world we talk about world obesity and the idea that all of us play a role and all of us are doing some good work in helping our patients take care of them and Reducing the risk of diabetes. So with that I'm going to end. I think I have hit like the 20-minute mark And I'm gonna stop there. I'm gonna pass it on to dr Argwell, I think what we'll do is we'll convey questions at the end But again, just a sort of whirlwind talk about obesity the pandemic really the growing role of telehealth I think which is really gonna or has changed the way we care for our patients We talked about screening different dietary patterns, particularly looking intermittent fasting Mediterranean diet And then also talking about some changes in legislation that hopefully will come about the next few years Okay Thank you Thank You, dr. Srinath for a wonderful talk So my next next 30 minutes or so is my presentation on the year-end review for obesity and nutrition I'll mainly cover the topics related to medications and bariatric surgery I have no disclosures but I'm going to discuss some medications which are in phase 2 and phase 3 trials and have not been approved by FDA for weight loss This is the recap of my present of my outline of my presentation I'm going to talk briefly about some of the activities that DSA and obesity and nutrition has done last year and Followed by some discussion about anti-obesity medications. We had a wonderful plenary session by dr. Garvey So we already have a very strong foundation in medications so I'll briefly go over that and then some articles related to bariatrics and Endo bariatrics and in the end a little bit about RDS and obesity and nutrition so a quick recap of 2021 and 2022 ACE is ACE understands the importance of obesity as a chronic disease and the importance of addressing it So there were two initiatives that were done by ACE among other things one of them was the ACE initiative to study the Attitudes perception and practices of endocrinologists in managing obesity It was a survey study and it gave us interesting insight into the patterns of practice among endocrinologists and as a clinician, I'm always interested in understanding how clinicians manage obesity and what are some of the barriers towards managing obesity and what was found in this study was What was found was that in this study some of the barriers that the endocrinologist highlighted were the cost, the lack of insurance coverage for evidence-based medications, poor patient engagement, and also having problems with access to healthy foods, and role of social determinants of health, so those were some of the barriers that we endocrinologists and clinicians had to deal with. One of the interesting findings, which we have observed across different disciplines is that weight loss medications and and bariatric surgery is underutilized. It is not frequently recommended for obesity management and it is not being utilized to its fullest and some of the papers that I have selected for this review emphasize on the importance of considering these options for obesity management. The second initiative that I want to share is that ACE created an obesity and nutrition annual conference. This year we had the inaugural conference that was in Tucson, Arizona. It was very well received. This was the first face-to-face conference we had in two years and the focus was obesity bias, role of social determinants of health in managing obesity. So ACE has taken this initiative about addressing this and having a dedicated conference every year to focus on that aspect and also nutrition. Moving on to obesity and mortality. So obesity is a chronic disease. It's a relapsing progressive disease and it should be managed accordingly. When it comes to obesity, we know from that it leads to several different cancers. It can contribute to more than 100 diseases. So this recent study, what they did was they created a program, a micro simulation that mimics the national representation of U.S. adult population based on the data from BRFSS and what they found was that excess weight was responsible for about 1,300 excess deaths per day. That's about half a million per year. So this is the data analysis from what happens with obesity. The life expectancy is reduced by 2.4 years and then the relative excess mortality was much higher for women as compared to men, almost double. So those were some of the findings that how obesity contributes to mortality and that's why it's very important that we address obesity with the same passion as we do other diseases. Moving on to anti-obesity medicines, as alluded earlier, that they are underutilized. There is a lot of hesitancy in using weight loss medicines for management of obesity. So to start with, now there are newer drugs. There's a lot of weight loss with some newer drugs that are out there. But we should also remember that there's older drugs that have been there for a long time. We know about them. Maybe the weight loss may not be as impressive, but then these drugs, their treatment has to be individualized. Much of the care is dictated by insurance coverage. So we have to keep in mind all the medications available to us. Sometimes we have to use two or three agents in managing obesity. Sometimes we have to use medications after pediatric surgery. So having that whole panel available to us. So this was a meta-analysis done on pentramine and topramate that looked at six randomized control trials. There was a lot of heterogeneity, but overall there was a relatively acceptable safety and tolerability profile of pentramine and topramate combination. The weight loss with this combination was approximately eight kilos at 56 weeks. The analysis found that when the medication is continued beyond that, there may not be much more weight loss. And again, the response may vary. Some patients may continue to lose more weight. But overall, beyond 56 weeks, the weight loss was not that impressive and may have stabilized. But we do see weight maintenance when we look at it at 108 weeks. So with the combination therapy, about eight kilos of weight loss. Now if you look at the differences with the dose, the weight loss can vary from three to eight kilos. And about 5% of the patients who take this combination can lose up to 15% or more weight. So that's about that. As far as the side effects go, dyskinesia, paresthesia, and dry mouth were the most common ones. It has been shown in these studies that pentramine and topramate can reduce waist circumference, blood pressure, blood sugar, and lipid levels. So it's a good drug. And in certain patients, maybe this is our only option. Moving on to the next study, which looked at about 143 trials that had more than 50,000 participants. And what they looked at was trying to figure out the high to moderate certainty evidence. And they found that pentramine, topramate, and GLP-1 receptor agonist were among the most effective agents in reducing obesity. In post hoc analysis, because the way the data was run, semi-glutide was added towards the end. They found that it was very effective, both for more than 5% weight loss and the person body weight change. So and it has a similar risk profile compared to other drugs that were studied. So in this network analysis, if you see the authors characterize this, just an easy infographic to understand, that the ones with the dark green is more beneficial than the standard lifestyle change. And on the other side, the orange is for the harm outcomes, possible adverse effects. So if you see pentramine and topramate and GLP-1 receptor agonist stand out, they have the best outcomes when compared to lifestyle alone. And on the other side of the spectrum, naltreoxia and buprenorphine, and to a certain extent pentramine and topramate can have more side effects and adverse effects. So that is the spectrum. And when we prescribe these medicines or we discuss about these medicines, it is important to inform the patients to have a shared decision making when we are trying to select the medicine that would work best for the patient. Moving on to the next study, which is an excellent study that was recently published. So oftentimes when we are prescribing these medicines, yes, we get weight loss patients too well, but what happens after some time? There's weight regain. And it's a huge challenge to manage this weight regain, this problem of weight regain. So what this study did, every participant had to go through an eight weeks of low calorie diet. And after eight weeks, they were randomized to four groups for a year. And the groups included exercise with placebo, lirigutide with usual activity, lirigutide with exercise, so that's the combination, or placebo with usual activity. So these are the four subgroups that they did after the low calorie meal plan. So in this study, if you look at the first graph here, you will see the most effective one was exercise with lirigutide. That had the most effective weight loss over 52 weeks. And the second one that looks at the change in body fat percent. So on that body fat percent, the change with exercise and lirigutide was 3.9% in the percent body fat, compared to exercise and lirigutide alone, which was 1.7 and 1.9. So almost double when we used the drug and exercise together, when we used them separately. And you can see after the low calorie phase ended, this gray box, and you can see the trend, placebo is coming back up, the other three are coming down, they're still down, and the best one is exercise and lirigutide. The other important thing that was found was that there was more weight loss, about 15% from baseline, when it was observed with the combination group than just with 10% with the exercise group. So we had a great session on exercise, there was emphasis on lifestyle with exercise, behavioral therapy, and exercise, so that combination is helpful. Why this study is important is because it suggests and it encourages a multi-modal approach to weight management, moderate to vigorous intensity exercise programs with lirigutide treatment after diet-induced weight loss were more effective in improving weight maintenance compared to just having either exercise or medications. So that is one of the take-home messages for our patients when we make recommendations. Now this is a summary slide of STEP trials for semiglutide, and they will be covered in several different sessions. Some of these were covered last year in the year-end review, but I want to give you a quick review so we can talk about the other STEP trials that came out this year. So STEP2 was the only trial that had patients with type 2 diabetes, the others were without type 2 diabetes, they had obesity or overweight with other comorbidities. In the first study, STEP1, it was semiglutide 2.4 versus placebo. In other studies there was combination, either different doses or with intensive behavioral therapy. And in STEP4, which is an interesting study, they initially gave semiglutide for 20 weeks and then randomized them to either semiglutide or placebo and to see what happens. So notably, if you see the weight loss in these groups, there was significant weight. 68 to 86% of the participants lost more than 5% weight. That is a remarkable thing for participants to lose. If we just looked at another drug earlier, the percentage of patients losing 5% body weight was much less. So if we prescribe this, the likelihood of success is much higher. The other thing that comes to, when we look at this data, is that the mean weight loss ranges from 9% to 16% in these trials. And in STEP4 trial, where after 20 weeks we stopped the medicine or we continued placebo versus semiglutide, from week 20 to week 68, there was a 7.9% additional weight loss in participants who continued the medicine versus participants who were on placebo who actually gained weight. That's a 6.9% gain. If you look at the difference, that's a lot. Why this is important is oftentimes when weight loss medications are addressed or people are more critical about these medicines, it's like, okay, they are forever. We prescribe blood pressure medicines, we prescribe diabetes medicines, and we are okay for them to be taken for lifelong. So this obesity is a chronic disease. If we stop therapy, then there will be weight regain. But there are medications which are safer, which we can continue longer. So this, after STEP4, this is an interesting segue into the extension. This just came out, STEP1 trial extension. So what they did was, when this first study ended at 68 weeks, they continued to observe a small cohort of patients who now do not have any lifestyle interventions. They can do it on their own, but not being followed for lifestyle interventions or recommended. And they observed this group. And what they found was there was some weight regain, but it was still less than their baseline. So if the medication is stopped, the semiglutide, placebo, everything was stopped, the study showed there will be weight regain, and that's why it's important to continue this drug. So this study reinforces the need for continued treatment to maintain weight loss and cardiometabolic benefits. Because what happened was, when the patient started to regain weight, there was also loss of those cardiometabolic benefits. So STEP4 trial and STEP1 trial extension both emphasize on the importance of continuing these medications long-term, so we can see continued benefit with these medications. Moving on to STEP6 trial. So this trial came out this year. So this was a study that was done in South Korea and Japan. There were adults age 18 in South Korea, more than 20 and above in Japan. And basically the distribution was semiglutide 2.4, 1.7, or placebo. And what this found was, if you see the difference, there was 13.2% weight loss with semiglutide 2.4 compared to 2% in placebo. About 83% of the participants who were on this medication in the study, 2.4 milligrams, lost greater than 5% of the body weight. There were GI disorders, more GI complaints in participants who were on semiglutide, and that was about 60% versus 30% in placebo group. So that was there, and we have seen that in other trials too. As far as the adverse events goes, it was about 3% in semiglutide 2.4 compared to 1% in placebo group. So this study makes it clear that this medication can be used in East Asian population, and it's a promising drug for weight management. Moving on to STEP8 trial, that's the next trial that was done for randomized controlled trial for people with obesity without diabetes. The participants were randomized to receive either semiglutide, liriglutide, or placebo, and there was dose titration done. So the mean weight loss, it's a comparison of semiglutide and liriglutide, and if you see there with semiglutide, the weight loss was about 15%, with liriglutide about 6.4%, and placebo around 2%. And for all person, 10%, 15%, and 20% weight loss range, semiglutide did better than liriglutide. So that's a comparison. As far as discontinuation of the drug because of adverse effects, actually there were more participants who discontinued with liriglutide. Probably it's a daily dose, more nausea, more GI discomfort compared to semiglutide. As far as GI effects goes, both groups had significant GI effects, adverse effects, maybe nausea, some abdominal discomfort, which ranges from 82 to 84%. So clearly semiglutide is more effective, but again, insurance dictates what medications we prescribe, so there are some limitations. Liriglutide is good, and that's the comparison of those two drugs in step eight. This is the meta-analysis that came out, I think, last week or the week before. There are actually two meta-analyses, I've only included one. One goes over the GI side effects of semiglutide, and the other one, just as a group, GLP-1, receptor agonist, and the concern with gallbladder issues. So 76 randomized controlled trials were included in this study. And in this study, they looked at the effect, the biliary disorders, the gallbladder problems with this GLP-1 receptor agonist, and there was increased risk of gallbladder disease, biliary disease. Spatially, they found that when this was used in higher doses for longer periods of time, and in patients for weight loss rather than diabetes. So when we are prescribing it for obesity, we use the higher dose, we prescribe it for a longer time. So this is something that we have to discuss with our patients. And if you see, there's some gallbladder disease, cholelithiasis, cholecystitis, biliary disease, some cholecystectomies, so those are the main ones. And if you look on the other side of the panel, looking at different GLP-1 receptor agonists and the effect with the gallbladder disease, you can see oral semiglutide did better than subcutaneous semiglutide. Lidoglutide had more issues with the gallbladder disease and disorder. So this is something to consider and keep in mind and educate our patients. If they have symptoms, they can seek medical attention in a timely manner. Moving on to the next drug, craglinotide. This was discussed this morning, so I'll be very brief. Amylin is a pancreatic beta cell hormone. It increases satiety, it slows gastric emptying. So this medication is a long-acting amylin analog, works similar to that. It reduces food intake and reduces body weight. And you can see it acts in the gastric delaying, but also it helps with the homeostatic and hedonic brain regions. So this is the newer medication, again, right now in trials. In phase one trial, a randomized placebo-controlled phase one trial of adults between age 18 to 55, BMI 27 to 39, otherwise healthy, were enrolled in this trial with having once weekly subcutaneous craglinotide or matched placebo in combination with semiglutide. So that was the distribution. And if you see on here, on this side, there are different doses of craglinotide. And the last one is pooled placebo with semiglutide. So we have just had looked at all the step trials and how effective they were, how good step eight showed semiglutide was. So in this, we have used that with this drug or placebo. And if you see here, with all the different doses, you can see from 8 to 17% weight loss. The most weight loss was with the dose of 1.2 and 2.4 milligrams. And this was without lifestyle changes. So most trials have intensive behavioral therapy or lifestyle changes. In this trial, they were looking at phase one trial more for the safety of the medication. So the weight loss ranged from 8 to 17%. That was somewhere there. And on the other side here, you can see the combination of craglinotide 4.5 with semiglutide and matched placebo with semiglutide. So that was the most effective medicine so far. And now we have this combination, which has a potential for about 15% weight loss compared to 8% with the other drug. So this opens the potential for these two drugs have a different mechanism of action. So if we can combine that, use combination therapy, and we know that our patients who have obesity need multiple therapies, multiple modalities to manage their weight. So that would be an excellent combination therapy for our patients with obesity. So the second study is a phase two trial, randomized double-blind trial. Phase two at 57 sites. And adults with BMI at least 30 or 27 with hypertension or dyslipidemia. There were different doses of the craglinotide and once a week litigatide, once daily litigatide or placebo. The primary endpoint was change in body weight from baseline to 26 weeks. So this is the data. And if you see here, the weight loss with different doses. So this is 4.5 milligrams, the highest dose. And the weight loss is around 10%. It ranges from 6 to 10% based on dose. And the weight loss at 26 weeks was 8.4 with litigatide. So this is, and if you see here, about 87% of the participants were able to lose 5% or more. 53% lost more than 10% of their body weight. So this study that was done for 26 weeks had more weight loss with this drug compared to many of the trials that have been done for 52 to 54 weeks for different, for medications like naltrexone, buprenone, orlistat, and for litigatide. So this is more weight loss in 26 weeks and has the potential to be used as combination therapy once we have some more trial data. Moving on to the next medicine, terzapetide. These are all tongue twisters for me. So GLP-1 and GIP-1 agonist, dual agonist, it helps with controlling the appetite, decreasing food intake. That's one. It increases insulin secretion and also helps with reducing gastric emptying, increasing satiety. So those are the mechanisms for this drug to work. This is a summary slide of SURPASS trials, 1 to 5, and these trials were not done for weight loss. The primary objective of these studies was to study people with type 2 diabetes. But their secondary endpoint in these trials were weight loss. One of them was how mean reduction in body weight from baseline, and the other one was percentage of those who achieved weight loss more than 5, 10, or 15 percent. So we are just looking at the secondary outcome data. So if you see based on the doses here in this column, the weight loss was ranging, was quite impressive with this. The average weight loss was 5 to 12 kilos based on the dose. Approximately 75 to 80 percent lost more than 5 percent of their body weight with 15 milligram dose. 25 to 69 percent lost more than 10 percent, and 27 to 43 percent lost more than 20 percent of their body weight with the higher dose of 15 milligram. So this is consistently we are seeing large percentage of participants losing 10, 15, 20 percent of body weight, which is very impressive. The adverse effect profile was similar to many of the other medications that we currently prescribe. So this is the data from SIRPRESS, and this is the first study that just came out last week, SIRMOUNT1, and it's yet to be published. It's just some initial data that has been released. So this is the first time this has been studied as a dedicated trial. The SIRMOUNT series is for weight loss, for obesity. To study dedicated for obesity, the participants were randomized to 5, 10, and 15 milligrams versus placebo as an adjunct to lifestyle changes in adults without type 2 diabetes who have obesity or overweight with at least one comorbidity. And what is impressive is 63 percent of the participants achieved at least 20 percent weight loss with 15 milligram dose. And as a reference point, when many times we have sleeve gastrectomy, endoscopic procedures, and the weight loss could be more than 20 percent, but many times it's more like 15, 18 percent. So now we have a drug that can potentially, 63 percent of the participants lost more than 20 percent of their body weight, 89 percent and 96 percent of the participants achieved at least 5 percent weight loss. So 96 percent with 10 and 15 milligram dose lost more than 5 percent of their body weight. So this accounts for the second generation of weight loss medicines that Dr. Garvey was referring this morning. As far as the adverse effect goes, most common was GI adverse effects. Nausea was the most common one, which was much higher, about 30 percent in the drug arm versus 10 percent in the placebo arm. And the discontinuation rate was double in the drug arm, about 4 to 7 percent compared to about 2 percent in placebo. So that was the difference in the treatment discontinuation, 4.7 percent. So moving on to the next part of this talk is metabolic and bariatric surgery and endobariatrics. And the papers that I have selected is more from a clinician standpoint, so I'm looking at something, talking to my patient in the clinic, what are some of the relevant papers. And there are many that are excellent, but we can only cover a few. So as in the previous talk, Dr. Srinath alluded to how COVID-19 has affected how we manage obesity and any disease, how different it has affected how we provide patient care. So when it comes to bariatric surgery, there was a 12 percent reduction in cases since COVID-19, because most of the procedures could not be done. The participants who actually received surgery, they were younger, healthier, probably high risk group didn't want to have surgery, or the healthcare teams felt it would not be fit for them to get surgery at this time. And sleeve gastrectomy was the predominant procedure, which has been for several years. So we see about 74 percent of the procedures were sleeves versus Roux-en-Y. And this was a reduction overall in the bariatric surgery. So when we look at bariatric surgery, we know very well it can improve outcomes with diabetes. It reduces the cardiovascular risk factors. But what about cardiovascular disease? Do we have data to say that there is reduction in cardiovascular disease? So this meta-analysis looked at 39 studies and compared bariatric surgery patients with non-surgical controls and was trying to see the effect on these following all-cause and cardiovascular mortality and heart disease. So what it found, this meta-analysis, was there is beneficial effect in all-cause mortality and cardiovascular mortality. There is reduced incidence of heart failure, MI, and stroke in patients who have bariatric surgery compared to controls. But there was no significant improvement in atrial fibrillation. So there is benefit in cardiovascular risk factors, there's benefit in cardiovascular disease when we take into consideration bariatric surgery. What about stroke? What do we know about stroke? Yes, cardiovascular health improves. So in this study, they looked at about 70,000 patients who had metabolic and bariatric surgery and compared with eligible controls. And they found at one year, the risk of having ischemic stroke was 0.6% compared to 1.2% in controls and the benefit persisted even at five years. So with bariatric surgery, there was reduced risk of stroke following weight loss from the surgery compared to patients who did not receive work controls for this study. Moving on to the next study, oftentimes we see patients in clinic who have excess weight and they cannot get their orthopedic procedure, whether it's hip replacement, knee replacement, the procedure is delayed or canceled, or they are advised to lose weight and come back when their BMI is at a certain point. So this study looks at this clinically relevant question that we encounter frequently in our clinics, is what happens if we do bariatric surgery before total knee arthroplasty? Would it change anything? So when they look at this, they took about, I think, 80 patients, 82 patients were enrolled in this study, and then they looked at, they randomized them into 41 patients had bariatric surgery and 41 other patients have usual weight management advice. And what they found was at the end, there was a six-point difference in the BMI in patients who received bariatric surgery. And the other thing was that the outcomes of TKA, of total knee arthroplasty, were much better in patients who had bariatric surgery, had lost weight. And also that there were fewer patients requiring the knee arthroplasty because with bariatric surgery they had less pain and they could go without surgery. So there was definite improvement and fewer participants required TKA after weight loss. So that is something relevant, rather than our patients being in pain, unable to ambulate, having depression from inactivity, recommending bariatric surgery in certain cases to lose weight to be eligible for or have better outcomes from the surgery, TKA surgery. This next study looks at type patients with type 1 diabetes. So we have a lot of data on bariatric surgery and type 2 diabetes, but we have limited data in type 1 patients. So this study looks at about patients who have type 1 diabetes and their insulin requirement and requirement for medications post-bariatric surgery. And there was a significant improvement in insulin doses from about 120 units to 60 units two years post-operatively, and they required fewer medications for controlling, managing their diabetes and other diseases. So this is important because oftentimes we entertain the idea of bariatric surgery in type 2, but with increasing obesity, several of our patients with type 1 also struggle with obesity. So this could be an option and they would require less insulin, less medications post-surgery. This next study is about patients with type 2 diabetes, and I will spend a little bit more time on this. This is interesting data. They looked at about 170,000 participants who had bariatric surgery. So these patients, they looked at what was the effect on their longevity and also life expectancy. So it was six years more longer than if they had received bariatric or metabolic surgery compared to usual care. So that was one of the findings. The other finding was when they did the subgroup analysis, they looked at people with diabetes and people without diabetes, and they found that their mean life expectancy was nine years longer in people with diabetes who had bariatric surgery compared to people in subgroup analysis who did not have diabetes, the life expectancy increased by about five years. So this is important because there was more benefit in people with diabetes nine years. So that is something to consider making this recommendation to our patients who have type 2 diabetes and obesity. The other finding was, and this was in the 10-year time frame, if we look at the number needed to treat, it would be about eight for people with diabetes and about 30 for people without diabetes to change these outcomes. So this is something to take into consideration and recommend this to our patients when necessary because it can improve life expectancy and has a greater impact in patients with diabetes. So when we make this recommendation about diabetes and getting cured or going into remission with bariatric surgery, we often encounter this problem of relapse, that after a few years being in remission, the diabetes is there, there is relapse. And for this study, the post-operative relapse of type 2 diabetes was defined as reintroduction of diabetes medications. So patients who had complete diabetes remission at two years post-surgery were the only ones included. So if they went into relapse sooner, then they were not included in this analysis. So they looked at what were some of the factors. Can we predict who would have a relapse of type 2 diabetes? Because then we can counsel them differently. And if they are going for surgery just for remission of type 2 diabetes, then there's a cohort where there is a higher risk of relapse. And what this study found was that people who have longer duration of type 2 diabetes, who have less well-controlled A1C prior to surgery, who require insulin, who have less significant post-operative weight loss, which is understandable, and women, they tend to have a higher chance of relapse of type 2 diabetes after bariatric surgery compared to people who do not have these factors that come into play. So day-to-day when we are seeing our patients, if they ask us about surgery, bariatric surgery, these are some factors that come into play. Certainly every patient is different, their outcome may be different, but these are some factors that come into play. The next point is about sleeve gastrectomy versus Roux-en-Y. When I see patients in clinic, they ask me which one is better, what should I do, and they will definitely have that discussion with their surgeon, but they do want to know from their clinician what would be a good option. So this retrospective study looked at about close to 95,000 patients, 60% had sleeve gastrectomy and 40% had Roux-en-Y, and they found that the cumulative incidence of mortality and complication is much less in sleeve gastrectomy. That seems great. So there is less re-intervention, less re-operation, but there is a higher chance of revision surgery. So that is something because there is a drift towards sleeve gastrectomy, but we have to keep in mind that people who have sleeve may require more revision in 5 to 10 years. And there's another study that has just come out that is looking at at least 15-year follow-up. So the problem is short-term we don't see these issues, but if we follow these patients long-term, we would see the impact, what is different between sleeve and Roux-en-Y. So this study looked at weight loss, remission of associated medical problems, conversion to Roux-en-Y, and quality of life. So they followed these patients for 15 years, and what they found was half of those patients who had sleeve gastrectomy required Roux-en-Y, and this is something we are seeing in practice We have had these patients who had sleeve 5 years, 10 years ago, coming back with severe GERD or some of them require Roux-en-Y because their weight has plateaued. So this is when they are counseling your patients, this is one of the things to keep in mind. Yes, there is less complication with surgical intervention, but there is a higher risk for conversion, for re-operations. And then looking at the people who were converted to Roux-en-Y, the weight loss was about 33 percent versus not converted, so not much of a difference here. And the cost, the overall associated medical problems, the quality of life was similar. The important thing is that they do require that, that cohort of sleeve gastrectomy does require higher revision surgery. The next study looks at endoscopic sleeve gastroplasty, because we have been talking about sleeve gastrectomy. So how about if we do this endoscopically, less invasive procedure, and this study looked at that, doing that, and 90 percent of the patients who had endoscopic gastroplasty were able to have more than 5 percent weight loss, so it's minimally invasive. The adverse reaction was about, adverse event was about 1 percent. No one had severe or fatal adverse effect. And 6 percent required repeat endoscopic sleeve gastroplasty. Maybe they didn't have enough restriction, so they required, and 1 percent required laparoscopic sleeve gastrectomy. So this is also an important modality. If we are recommending sleeve gastrectomy, we could consider endoscopic sleeve gastroplasty, because it's minimally invasive, and the results are good. This is the last study that I have to discuss that's about the adjustable intragastric balloons. So there's a lot of advances in endoscopic procedures, endobariatrics, and this study looked at about an open-label randomized control trial, looked at the mean endpoint of total weight loss, and what this found was that about 17 percent of the participants could not tolerate, because of GIFX, yes, the balloon had to be removed. But for the other patients who received this balloon, their weight loss was significant, and it was, and they did require adjustment, upward adjustment. So based on their response, many of these patients ended up requiring adjustment to their balloons. But after adjustment, you can see there is more weight loss. And when they looked at the data, six months after the balloon was removed, 74 percent of the participants still had greater than 40 percent weight loss maintenance. So even after six months, longer term, we see the effect of weight loss. So this is a procedure we could consider for bridging. Not everybody can directly go to Roux-en-Y. They may have multiple medical conditions, or they may bridge to lose some weight and then go to the next procedure. So that is something to take into consideration. And in my closing remarks, I want to express my gratitude to Ace's team and Ace's family. We have done a lot of projects together. I would like to invite people to join the DSN Obesity and Nutrition. We do a lot of things for education. We also have projects for our trainees, fellows, and residents. This is available for participation. You can participate in educational projects. You can lead educational projects. There's a lot Ace is doing with obesity and nutrition. So you are welcome to join. And if you have questions, I'm available after the presentation. These are some of the projects in the pipeline that Ace is coming up with their guidelines for obesity management. And Obesity Algorithm is working on a consensus statement for obesity bias. And we have our annual meeting planned for next year. Hope to see you there. Thank you so much. If anybody has any questions. Yes. Maybe it's a... Yeah. I'm Matthew from Savannah, Georgia. I have a quick question. I have a question about weight loss. What accounts for the difference between the weight loss that we see with the GLP-1RAs between people with diabetes and people without diabetes? Why is there that difference? Because it seems pretty significant. In the population that I have taken care of, I feel like there's not that much of a difference. But I believe there's a component of insulin resistance, there may be some lifestyle changes or lifestyle choices that may be there with type 2 diabetes. There's also genetic predisposition. So those factors come into play. But the results in both cohorts are significantly good. And of course, with the type 2 diabetes, if they lose weight, they also benefit from a better control of their diabetes. So their microvascular and macrovascular complications are addressed too. So we see more bang for our buck in the patients with diabetes, but the response is good even in patients without diabetes. Absolutely. Thank you. Thank you. Olga Kaloff, Los Angeles. Great lectures. I appreciate it. Thank you. I appreciate hearing them. Question. If anything's been looked at, at some of the newer ways of addressing obesity and weight loss. Some of these apps that are coming out, like Noom, the way they approach it is not so much dietary, but more like psychological. Is there any way to address that? 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presentation

Dr. Reshmi Srinath

obesity

nutrition

COVID-19

telehealth

weight loss

Mediterranean diet

intermittent fasting

bariatric surgery

research initiatives