The 2025 EASO Algorithm for the Management of Obesity

Comments & Resources

Key Takeaways
The 2025 EASO Algorithm builds on the EASO Framework for the Diagnosis, Staging and Management of Obesity in Adults, which defines obesity as an adiposity-based chronic disease (ABCD) requiring structured assessment and multidisciplinary care. The Framework establishes how obesity should be diagnosed and staged, while the Algorithm provides guidance for the pharmacological management of obesity and its complications. Together, they support clinicians in moving beyond BMI-only definitions toward complication-based staging and personalised care. Speakers emphasised that obesity management should prioritise improvements in patient health, function and quality of life, rather than weight reduction alone.

Framework and Disease Staging

The EASO Framework highlights that obesity diagnosis requires assessment of adiposity alongside clinical complications and functional impact. BMI alone does not adequately reflect adipose distribution or disease severity.

Diagnosis and staging consider:

• Adiposity assessment using anthropometric indicators
• Cardiometabolic, mechanical and psychological complications
• Functional limitations and disease progression

This approach aligns obesity care with other chronic diseases by linking disease stage and complication burden to the intensity of treatment required.

Clinical Decision-Making and Personalised Care

The 2025 Algorithm for the Pharmacological Management of Obesity translates disease staging into a structured pathway to guide the use of obesity management medications based on individual patient profiles and complications. Pharmacotherapy is intended to be used as part of comprehensive obesity management within a multidisciplinary care pathway, alongside behavioural interventions, nutrition, exercise training, psychological support and, where appropriate, surgical procedures.

Implementation in Practice

Applying the Framework and Algorithm in practice requires recognition of disease stage, complication profile and agreed treatment goals. Multidisciplinary collaboration and shared decision-making are central to supporting personalised, long-term obesity care.

Future Directions and Next Steps

• Incorporate complication-based staging into routine clinical assessment
• Evaluate outcomes beyond BMI, including metabolic health, function and quality of life
• Use the Algorithm to support more structured and personalised decisions on obesity management medications within multidisciplinary care pathways

Resources

EASO Framework for the Diagnosis, Staging and Management of Obesity in Adults – Nature Medicine

• Nature Medicine publication: https://doi.org/10.1038/s41591-024-03095-3 
• Summary information
• Infographic

2025 EASO Algorithm for the Management of Obesity and Complications

• Nature Medicine publication: https://doi.org/10.1038/s41591-025-03765-w
• Summary information
• Infographic

Summaries are AI-generated from meeting transcripts.

Transcripts are auto generated, if you spot an error, please email enquiries@easo.org

Speaker 1 • 00:01
Hello everyone. Good morning, good afternoon, wherever you are across Europe and the world. It’s a real pleasure to be chairing this webinar today, which is this month’s YASO Collaborating Centers for Obesity Management webinar. And it’s entitled the 2025 YASO Algorithm for the Management of Obesity. So what we’re going to be doing, first of all, is take you through the framework, the YASO framework, which really focuses more on the diagnosis of obesity. And that will be presented by Professor Dekker from Tel Aviv. And then we’re going to be moving on to presenting the actual algorithm itself. And this will be done by Dr. Andrea Sudin. She’s the co-chair of the obesity management working group for YASO. So just a few bits before we get started, just to inform everybody that this webinar is being recorded and it will be uploaded to the ASO video archive soon after the session. Like I said, these are monthly webinars and they’re really the purpose is to share knowledge and expertise across the ASO comms. Those are the centers of obesity management network to really enhance obesity management and patient care across Europe and beyond. and we encourage attendees to share the webinars with colleagues as well. We will also ask you to get involved with Q&A. So we’re going to be speaking for about 30, 35 minutes altogether. And then there’ll be a chance to ask lots of questions. So please do get involved ’cause that’s always the best part of the session. And at the end, we will ask you to complete a feedback questionnaire which will really help us to improve these webinars going forward and take your feedback back. Finally, I’d like to just remind everybody about the European Congress of Abizid, the Eco-Congress that’s taking place in Istanbul in Turkey between the 12th and 15th of May, 2026, and we hope to see as many of you there. And of course we will be presenting the 2026 updated algorithm version of today, so we hope to see you there. I think it’s going to be really, really exciting. And just to remind you that late break in abstracts and early registrations are open until the 27th of February, 2026. So without further ado, I’d like to introduce our first speaker who probably needs no introduction ’cause he’s well-known in this space, a professor, Draud Dicke, who is a professor of internal medicine from the University of Tel Aviv. He’s also the co-chair of the Collaborative Incentives for obesity management for EASO. And he’s going to take us through the first part of the talk touching upon the framework. Joel, over to you.

Speaker 2 • 02:54
– Thank you, Barbara. I hope you see my presentation. And it’s really honored to present the first part of the new framework of obesity diagnosis, staging and management. So here are my disclosures, and I don’t have any disclosure regarding this talk. So we are very well know that BMI is not really defining very well obesity disease due to the fact that it’s not localized the fat or the adipose tissue and it’s not really implying what is the function of the adipose tissue. And this is the reason that we really worked very hard on this new IASO framework. I want to take you at least in two parts of this journey, and then Andrea will keep on this journey on the treatment. So let’s start with the first stage or first step of the diagnosis. So we’re really believing that to define obesity, we need much more than just BMI, as I alluded before. So we divided into the framework or the definition into two parts, the entrepreneurial part and the clinical part. Of course, BMI above 30, we still think that it’s really defined obesity, but we add another part in which BMI between 25 and 30 and waist to height ratio above 0.5 is another anthropometric measurement that defined obesity as long as there is another clinical complication of obesity. So you need three criteria, BMI 25 to 30, waist to height ratio above 0.5, and another clinical, meaning medical function or mental criteria according to defined obesity. So why did we choose waist to height ratio as the anthropometric measurement? If you compare waist to height ratio to BMI in order to really predict visceral adipose tissues, waist to height ratio is much better than BMI defining visceral adipose tissue. And if you want to predict 10 years risk of atherosclerotic cardiovascular disease, still waist to height ratio is much better predictor than BMI. So we thought that waist to height ratio is a better predictor of adipose tissue function. That’s why we suggested waist to height ratio as the anthropometric measurement and not just BMI. Why we choose the area of overweight. In the past, we used to look on overweight as an healthy stage, but in this paper that we published very recently, you can clearly see that in many countries, in many registry, those who are in the part of overweight, 60% of them had at least one obesity complication that relate to their obesity disease, meaning that over it in some parts are really obesity disease. Now we want to validate the IASO framework and we took the enhanced cohort, more than 44,000 patients. And what we found there that if you look and put the IASO criteria on this cohort, we found that nearly 19% of them fulfilled the criteria of obesity in the range of overweight. Okay. Nearly 60% of the overweight cohort had diabetes meditus. Nearly 80% had hypertension. And again, 60% of the overweight between 25 and 30 fulfilled the criteria of obesity due to the fact that they had obesity complication that we really mentioned before. So in this work, we really validated this criteria on the cohort of the enhanced. In addition to the fulfillment of the criteria, we also found that the new framework really defined patients that have 50% higher risk of mortality compared to patients with normal weight without comorbidities. Again, so these criteria, those cohorts that fulfill the criteria of the newbies by YASO had 50% higher risk of mortality and we have to really find those patients and define them as people living with obesity. Just to highlight this point, I just want to bring another paper that we published very recently. We took more than 1 million adolescents in the age of 17, and we followed them for five years in order to see what happens and which health status they will have five years later, according to the BMI in the age of 17. And what we found in boys and in girls, that according to the BMI in the age of 17, you can see five years later, the risk of developing obesity complications. And I want to really emphasize the fact that if we took those boys and girls that lived And with overweight in the age of 70, they still have 21% and 27% to develop five years later obesity complications, obesity-related complications, meaning again that this area of overweight between 25 to 30 is not in healthy status if you have the other two criteria. So we have to find those patients that are fulfilling the criteria of YAS definition of obesity. If we look on the complication that those adolescents really present five years later, we can see that they have doubled risk for circulatory system, 24 risk of endocrinic and metabolic disease. And you can see all the risks in those patients that lived with obesity in the age of 17. Now this is our suggestion for the new definition of obesity. What about the targets? What are the targets that we should really treat those patients to? So in every other disease, we have very fixed data or fixed targets. In diabetes, we have hemoglobin A1c. In hypertension, we have blood pressure below 130 and 80. In this epidemic, we have LDL targets. In obesity, we have percentage targets. So Luca Busetto and his colleague really wanted to define a fixed targets, not percentage targets. And they did a remarkable work on more than 45,000 UK adults. And they really showed us that the level below those targets are much healthier than those targets. So meaning if you have lower waist to height ratio than 0.53, the risk to develop metabolic and other complication is much lower than above 0.53. And again, the risk to develop obesity-related complication above 27 is much higher than lower. So those are the new targets that they suggested. And if we look on the graphs, the area under the curve for type 2 diabetes, atherosclerotic cardiovascular disease, you clearly see that the waist to height ratio is much more predictive than BMI. But if we look on the osteoarthritis, the heaviness disease, BMI is much more predictive than waist to height ratio. And if you look on the hypertension, it’s the same because hypertension is a unique complication that it’s relate to the heaviness disease and also to the metabolic disease. So now we have a suggestion for new targets. So let’s validate them. So in the study of the Sermont 5 they really compared trizepatide to semaglutide, you clearly see that trizepatide bring much more weight loss than semaglutide. But Karl LaRue wanted to take this study and to validate the new targets and to see what will happen. And what he showed us that if you look on the percentage of patients that reach those targets below 27, below Oestrohydr ratio 0.53, and below both criteria, you can see the percentage of patients that reach those targets with trizepatide and semaglutide. But if you look on the cardiometabolic complication, again, you can see that those patients that reach those targets nearly completely normalize the targets or the complications. Now, in order to reach those targets, the patients needed to lose 32% of their baseline weight. Another presentation by Carla Rue took other study, the step up study, which use, which compare semaglutide 2.4 to semaglutide 7.2 the weight loss. And I want to draw your attention to the achievement of those targets. Now, this column, this column and this column are those subgroups that reach the targets of below 27 and below waist to height ratio of 0.53. And again, you can clearly see that those who reach those targets nearly completely normalize the risk factors or the cardiometabolic risk factors. So in these two studies, Carla Rue really validated that those targets are really very important. The only issue is that again, in this study, they had to lose nearly 32% of their baseline weight, which is a very high percentage of weight loss. but those who reach this weight loss really reach the targets. So now we have the definition and we have the targets. Very recently we sent for publication the paper that we really try to see what is the cutoff point for mortality. What I showed you, the cutoff point for complication, Luca Busetto work really found the cutoff point for obesity-related complication. We wanted to really validate the cutoff point for mortality. And again, we used the enhanced cohort and really tested on the enhanced cohort what are the waist to height ratio cutoff point for mortality. And what we found is that the 0.5 is too low. It’s not significantly predict mortality in those patients. And the cutoff point that we found for mortality is 0.58. Again, if you look on sex, age, and ethnicity, it’s different numbers. And what we will have to do in the future is to really see how we find the cutoff point according to sex and ethnic groups. So what I showed you is that in the journey of the IASA framework, we have a new definition, we have a new set of personalized targets, and now I think we will move to the new algorithm of treatment. And I want to ask my dear co-host, Professor Andrea Tzudin, to really present this part of the new framework. Thank you very much.

Speaker 1 • 16:27
Thank you very much, Dror, for that thought-stimulating introduction. And it is my real pleasure then to invite Dr. Andrea Studin, who is an endocrinologist from Spain, to take us through the 2025 algorithm. Andrea.

Speaker 3 • 16:46
Thank you. Thank you, Barbara, and thank you, Dror, for this beautiful presentation that opens the floor to the pharmacological treatment of obesity. So let me just start. You see the presentation, right?

Speaker 1 • 17:06
Yes, we do.

Speaker 3 • 17:07
Okay. So these are my conflicts of interest. As I always say, there are a lot of conflicts and actually none. Dror explained to you about an important change in the paradigm of definition of obesity that is an adipose-based disease. I always like to start my talks with this paper published in Lancet last year, actually during the obesity day on the 4th of March, speaking about the global, regional, and national prevalence of adult overrated obesity with forecast to 2050. So the point is that you all know that obesity is already very prevalent worldwide, but the provision is that in many geographical areas around the globe, the prevalence will significantly increase. And to me, this paper is like the ghost of future. You all may know the Charles Dickens novel, “Christmas Carol.” This is the ghost of the future. if we don’t change our ways, the way we are doing things and the way we are managing obesity in the present, this will be the future that we’ll have 25 years from now. So it’s really time to make a change. So what we wanted to do with this new algorithm for the pharmacological treatment of obesity actually was not to repeat the history, but to create history because it’s really time to change our ways. And let’s not forget that there is still a lot of shadow in the obesity management. This is a very, we are speaking about a very vulnerable population. Patients in people living with obesity were very stigmatized. They are very vulnerable. They are still very stigmatized in many places around the globe. So, and even in Europe. So first, the first step to properly manage and treat obesity is to understand the disease and proof that we understand the disease is that we are using the people first language. So please let’s use proper language when we speak and refer to patients living with obesity. Because what we have to do before is the first step to treat obesity as a chronic disease is to connect, reconnect with our patients. You all know the movie “Avatar” And the meaning of I see you means that I see who you really are and understand what’s happening to you. And this goes beyond the BMI. And this is our main message. Dror explained you the framework for the diagnosis, staging and management of obesity in adults. And you saw from the data that he presented that waist to height ratio, which is like a surrogate of visceral adiposity, which actually is the dysfunctional adipose tissue, is mainly related to metabolic alterations like type 2 diabetes, hypertension, and cardiovascular risk, while BMI, which is more like a body volume parameter, was related to mechanical complications. So this confirms a previous paper and work from IASCO that was speaking about two main phenotypes of obesity based on adiposity, the fat mass disease, which is mainly associated with mechanical complications like neostar tritis or sleep apnea, and sick fat disease, which is mainly associated with metabolic complications like with endocrine and immune responses with alterations like type 2 diabetes, heart failure, cardiovascular disease, and so on. So based on this basis, we tried to build the first algorithm for the pharmacological therapy of obesity. But before going into the detail of the algorithm, I would like to highlight that the algorithm that I will explain is not a guideline for the whole obesity management, but it’s just a guideline to fill a gap in the obesity management, because you all know that the obesity management starts with recommendations on healthy lifestyle. Then this means nutrition and physical exercise. We have a lot of guidelines on nutrition. We have guidelines on physical exercise, and these are two examples. Then patients can undergo bariatric surgery or pharmacotherapy. and this is the normal scheme of obesity management guideline. We have guidelines on bariatric surgery, which technique we can choose according to patient’s BMI normally and presence of complications, but there was no real guideline on how to choose among the drugs that are available currently for the management of obesity in Europe. So this was the purpose of this guideline. we do not recommend to start with drugs. This is not, I repeat, a global obesity management guideline, but comes to fill this gap here. So we published the methodology of the building of this first algorithm for the pharmacological treatment of obesity in Obesity Facts last year in July. When we described in detail the methodology, the panel was formed by several experts, endocrinologists, epidemiologists, the internees, clinical scientists, biologists, methodologists. And we are divided into the panel of experts that we voted and formulated the recommendation. And then we had an evidence review team that collected and analyzed all the available evidence, but they did not participate in defining the clinical questions, nor selecting the outcomes or formulating the recommendations. So they only managed the data. So we based this algorithm on the obesity management medication approved in Europe, like Orlistat, Naltrexone, Bupropion, Topiramate, Phentermine, Liraglutide, three milligrams per day, Semaglutide, 2.4 milligrams per week, 10 and 15 milligrams per week. A MEDLINE and InBase search was performed up to 21st of January, 2025. No clinical trial that’s what published and available after this date was included in the algorithm in the analysis. And we only used in the analysis the randomized clinical trials that enrolled patients either with BMI above 27 and at least one obesity related complication of patients with obesity defined by BMI above 30. And we compared different obesity management medication either versus placebo or no therapy on top to lifestyle intervention or active comparators with in this clinical trials head. We included randomized clinical trials with a duration of at least 48 weeks. Okay, so the decision to exclude non-randomized clinical trials was made due to methodological concerns with observational studies. So we only included randomized clinical trials with a longer duration. The panel of experts agreed to use the grading of recommendations, assessment, development, and evaluation, which is the grade methodology, formulated clinical questions using the PICO framework, identify several outcomes that we classify as critical, important, or less important after several internal discussions. So, for mixed systematic reviews, network meta-analysis were performed to rank the effectiveness and safety of the obesity management medication considered in the PLACEN guidelines for critical outcomes. The recommendations were formulated exclusively based on results of meta-analysis of either placebo-controlled randomized clinical trials or head-to-head randomized clinical trials. So the complete results of the systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults, you can find all the analysis here in this paper published in Nature Medicine. And in the same issue, the algorithm paper was published simultaneously. And this is a way for you to better understand where the recommendations from the figure that I will present came from. So you have here available all the results. So this is the framework for the pharmacological treatment of obesity and its complications from IASO that was published in Nature Medicine in October last year. And I will go step-by-step through this algorithm. As I mentioned before, this algorithm was based on this main concept of obesity that has no complications at present, which is the fat mass disease, let’s say, sorry, it has no complications when the patient is evaluated. And the goal to treat is that fat mass accumulation has to be treated to prevent dysfunction in non-adipose organs. Before going into more detail to the algorithm, it’s important to highlight that this is the first algorithm for the pharmacological management of obesity that is not based only on weight loss as a unique goal or objective for the treatment. And this is another important message that goals for the management of obesity have to be personalized and have to be adapted according to the condition of the patient. and not always the main goal have to be losing a certain amount of weight. We’ll see that we can have other goals. So if the patient has no complications, we want to prevent that this fat mass provokes dysfunction in non-adipose organs. And then the primary endpoint, the main objective is the total body weight loss. So these were the drugs that had significant impact on the total body weight loss listed by author in our analysis. It’s important to know that to highlight again that no clinical trial published after 21st of January was included in this analysis. Then if we go into the block of patients that have complications related to obesity, the goal to treat is to reverse dysfunction in non-adipose organs. this is the main goal. And if the patient has a fat mass disease and mainly has met mechanical complications like Neostar arthritis, by the date when we had our cutoff in time, only tirsepatide had, sorry, this is the sleep apnea, only tirsepatide had the clinical trial published showing significant results on the sleep apnea. And in the case of semaglutide, fentanyl, methopyramid, liraglutide, naltrexone, buprenorphine, and Olistat, they had no data available on sleep apnea. If the patient has a knee osteoarthritis, the drugs that had finished the clinical trials were semaglutide and liraglutide, and only semaglutide had a significant positive result in knee osteoarthritis, while the results from the clinical trials with liraglutide had no significance on this pathology. Okay, so regarding the primary outcomes in the sick fat disease, in the metabolic complications related to obesity, in the case of prediabetes, the primary endpoint was normal glycemia restoration and the drugs that had finished the clinical trials and showed significant positive results on these outcomes were with tirsepatide, semaglutide, liraglutide, and dorlistat being tirsepatide and semaglutide equal in their effect on this on normal glycemia restoration. In the case of type 2 diabetes, the primary outcome, the main goal is diabetes remission. Tirsepatide and semaglutide were the first ones with similar results on this outcome. Then liraglutide and naltrezone propropion also had positive significant results, but to a less lower impact than dermatic hepatitis and semaglutide. In patients with cardiovascular disease, the primary end point was the composite outcome, the base, and only semaglutide and naltrexone propropion had the clinical trials on this outcome, but both showed protective effect, but semaglutide effect was higher. You all know the results of the select trial showing a 20% reduction in this primary outcome. When it comes to heart failure, the main outcome was hospitalization for heart failure and the sepatide and semaglutide were the only drugs that had the clinical trials that fulfilled the criteria for the inclusion in the algorithm, both showing a positive significant effect in reducing the hospitalization for heart failure and they were equal in this effect. Regarding the MASH-LD, the metabolic fatty liver disease, the main outcome was the MASH remission. And I insist that we included the clinical trials published by the 31 of January. So the essence trial that was the phase three of semaglutide in MASH was not included in this algorithm. And from the clinical trials that were analyzed in this first algorithm, the excepatide and semaglutide were those that showed the positive effect and the excepatide came first in this analysis. Now we are preparing the second, the update of the algorithm of pharmacological treatment of obesity. And we will update the analysis with the clinical trials that fulfill the same inclusion criteria published after the 31 of January, 2025. – Thanks very much.

Speaker 1 • 32:24
And just to point out that this version that Drew has put up does actually have, well, semaglutide included in mash, but the actual original nature one did not for the reasons that Andrea explained, but that will get updated in the new version. Okay, fantastic. That’s great. So thank you very much both. So there’s lots of questions coming through. which is great. I’m going to, I guess I’ll start off with, gosh, there’s quite a few questions here. Let’s see. Okay, let me go first to Dror. I mean, I think there’s a question that says, how are obesity phenotypes considered under the framework? Dror, do you want to comment on that?

Speaker 2 • 33:12
– Well, I really don’t know how to answer that because I don’t understand the question, meaning that, what do you mean obesity phenotype? Meaning the phenotypes according to Costa, Professor Costa.

Speaker 1 • 33:25
– Yes, I guess people talk about different phenotypes and I guess are we clever enough at the moment to try and distinguish between these? Is there any evidence to support that?

Speaker 2 • 33:35
– So we had the decision to go to phenotype the treatment according to the complication. Professor Costa is phenotyping patients according to the machinery of weight gain, meaning hungry brain, hungry intestine, slow burning, and et cetera. And I think in the area of the GLP-1, GIP, GLP-1 amylin, the issue of the machinery of weight gain is really not so important because I see everyone is losing weight, even though if they are, most of them, even though they are slow burners. So I think that the phenotyping is less important than the complication. And I think we should really direct the treatment according to the complication because we have now much more evidence that the treatment is going beyond weight loss in the select and in the essence. And so we know that the molecular, the GLP-1 or the GLP-1-GIP is affecting the disease. In GLP-1 is the inflammation, the GLP-1-GIP is the fat mass, the disease, and not just the phenotype. So I think we should really stick with the complication direction, not just to the phenotype. This is my personality.

Speaker 1 • 35:18
– Thank you very much. And to some extent, you know, when we use medications, we still don’t have any evidence to suggest that certain people respond better than others. You know, at the outset, we sort of have to try and but it does sound that there was a generally good response on the whole for some of the newer increting therapies. Excellent. So I think there was a comment about children and whether some of the I guess the criteria apply to children you know this for the definition of obesity and I guess we’re not pediatric endocrinologists so I’m assuming that these we should stick to just

Speaker 2 • 35:55
adults only. But we have to we have to add here that there is a committee in the Yaso that working on a new framework for definition for the adolescents. So we will have a new framework for adolescents just you have to wait and I think we will publish it in Istanbul. So in a set in a

Speaker 1 • 36:16
dedicated session for adolescents. Fantastic that’s great. Andrei there’s a question that comes up about thyroid cancer and whether that is something that you take into consideration when you start these medications. Do you want to clarify a little bit about whether that’s an issue when we prescribe?

Speaker 3 • 36:40
Can you, I’m listening with interruptions, can you repeat please?

Speaker 1 • 36:46
Okay, so if a patient has thyroid cancer at the outset, is this a contraindication to to prescribing, for example?

Speaker 3 • 36:56
– Well, this is something that it’s written in the label of many of the increasing drugs, but actually in the clinical practice, there was no confirmation regarding the increase of risk of thyroid cancer and so on. So actually in the clinical practice, this is not a real concern for us. I don’t know what you think Barbara and Dror, but at least at my side, this is not a real contraindication.

Speaker 2 • 37:27
– No, only medullary thyroid cancer.

Speaker 3 • 37:30
– Yeah, the medullary, yeah, but other types of cancer, no.

Speaker 2 • 37:33
– No, absolutely, I agree.

Speaker 1 • 37:36
– Absolutely, okay. But going back to Dror, there’s a comment in the chat about phenotype. It says, “COSTA covered 85% of all patients “living with obesity in the study. “Phenotype is relevant, especially for looking for genetic obesity and also other phenotype like emotional eaters. I think there seems to be some, I don’t know whether you want to respond to that.

Speaker 2 • 38:01
– I absolutely agree. So there is red flag for monogenic obesity that I use a lot. If I really suspect in monogenic obesity or other, but if you look on the studies, let’s take the Sermon 5 that compare semaglutide to trisepatide, only 7% could not take GLP-1 or only 7% did not really react to GLP-1, 7 to 10%, meaning that 90% of patients that we are treating them with this combination are really reacting and losing weight. So I think this issue of phenotyping according to the pathophysiology is important, but in daily life, we will treat them with semaglutide or trisepatide. Saying that, I totally agree that if we have red flag for monogenic obesity and I have patients that did not lose weight with GLP-1 or could not really tolerate GLP-1, so then we have to really see what are the phenotype, what are the red flags and really did those patients made differently. So phenotype is important, but in real life we will give them GLP-1 or GLP and GIP. Thank you very much, Ror. And there is a question in the chat

Speaker 1 • 39:27
which refers to the Karl LaRue analysis, you know, in terms of remission. And I guess the question the anonymous speaker, a person who’s asking the question says they find patients still have significant residual risk even when a maximum GLP-1, for example, ACR is still raised. So the question is, you mentioned that large volumes of people had comprehensive risk factor resolution with GLP-1. They’re asking, was this in patient with no type 2 diabetes rather than in patients with type 2 diabetes? Can you comment?

Speaker 2 • 40:07
– Yeah, so the two presentation were the first one on the Sermont 5, which was not non-type 2 diabetic patient. And the second one was on the Step Up, again, non-type 2 diabetic patient, meaning patient living with obesity only. And of course there is residual risk. It’s not really a miracle medication, but he just proved, he is Professor Busetto, approved or validate the targets. So we have now targets that we have to validate them more, but on these two studies, those targets really showed us that those patients who reach those targets have much, much, much less risk to develop other cardiometabolic disease. And in some case, normalize, like normalize the glucose level, normalize the HDL levels, And so those targets are real. My problem is that to reach those targets, we have to lose 32% of weight. So it’s a huge reduction and it’s very difficult. And the second thing is that I think we should relate to the ethnic issue and the sex issue, because as I showed you in our submission, it’s totally different between men and women, like everything, and also according to ethnic origins. So we will have to develop this, to learn this, to study this, but this is the first step, and a very important first step.

Speaker 1 • 41:50
– Fantastic, thank you very much. There’s a question from Dr. Satish, who’s asking, why is CKD not added to the sick fat disease category? Andrea, do you want to comment on that? I mean, I think it’s because ultimately we don’t have any trials with 48 weeks duration with an endpoint of CKD for the treatment of obesity. I mean, so I think Andrea was quite clear and sometimes people ask why do we not have hypertension there? Again, hypertension is not a primary endpoint and again, mental health, depression, anxiety, other diseases, asthma, for example, there are trials going on in lots of different disease areas And I think it’s because we’re being quite strict with regards to the criteria and it has to be a primary endpoint. And hopefully we will see evidence for CKD, which of course is there for patients with type 2 diabetes, for the treatment of diabetes, but here we’re really focusing on obesity. So Andrea, there’s a question about when we diagnose obesity, we’d use the mechanical, mental and functional complications and when we follow up our patients, we see the results in metabolic and sometimes functional complications. Is there any data for psychological complications to insert them in the algorithm? Again, I probably should have answered that for you, go on.

Speaker 3 • 43:15
– I heard Andrea, but I don’t know what you said, sorry.

Speaker 1 • 43:20
– So the question is about, do we have data? – I can’t listen. – You can’t hear me. Can everybody else hear me?

Speaker 4 • 43:27
– Yes. – Yeah.

Speaker 1 • 43:29
We’re asking about psychological complications and why are they not in the algorithm? If you can’t hear me, then I will, I might have to put it in the chat, but essentially, you know, they’ve not been followed up in a sort of randomized clinical trial fashion and that’s why they’re not there, but they’re, they’re, they’re sort of real world data or or post hoc data that suggests that a lot of, I guess, complications, anxiety, depression, there does not seem to be certainly a worsening of these complications. And if anything, the data suggests there are improvements on the whole. And like I said, when we looked at large post hoc analysis, but this has not been, like I said, studied in a randomized fashion, and therefore it’s not reported here. Again, if there’s future trials, by all means, they will be included in the algorithm. So let me go back to draw then and regarding height and weight ratio, is there any variation for different ethnicities, given that Asian populations have shorter heights compared to European populations? Draw.

Speaker 2 • 44:39
We will have to, we will really have to look into it. instance, so our first publication really took at the end, Haynes, and we used 0.5. And then when we look on the mortality, the 0.5 were too low and not significant. And we look into the ethnic issue and the sex issue. And I think the waist to height ratio is much higher. And we will have to paper, very nice paper of the nice paper. And then there is a range, it’s not just point five, it’s a range. And they really say that I’m not sure this is the right and the fixed number. So we will have to find which is the fixed number, you know, I’m still in the age that diabetes was defined 140 milligram. And The same with blood pressure. We defined it 140 above 90 and now it’s 130 above 80. If you live in the States for diabetes, it’s 120 to 80. So it’s a moving area and we will have to find which are the real evidence for the true cutoff point. We start for 0.5. I’m sure we will change the 0.5 and we will see what are the true numbers. For instance, I saw a question there. When we look on the first paper on the enhanced, so two thirds of the overweight really fulfilled the criteria of FUJASO, meaning that like 58% of the cohort from the enhanced were defined as people living with obesity, which is of course very high. But then when we took the 0.58 cutoff point for mortality, only 10% from the overweight cohort had fulfilled the criteria. So I think we will have to look into it and to really find what are the true numbers and to really start to define obesity a little bit different, not just by BMI, but other anthropometric measurement and the medical component of obesity.

Speaker 1 • 47:12
– Thanks, Dror. And actually a question for me, because as we see, we, yes, we define obesity with this BMI of 25 and above, you know, between 25 and 30 using a waist to height ratio of over 0.5 plus one complication, but we’ve seen cutoff points of 0.53. And then you’ve talked about a cutoff point of 0.58 in terms of increased mortality. I mean, what should we do as clinicians? We should cut off, do we stick to the 0.5? ‘Cause there’s quite a lot of, it’s not confusion, but clearly we’re moving beyond BMI, but what should we be doing practically now?

Speaker 2 • 47:51
– So what we found again in the study that those patients that had BMI between 25 to 30 and had obesity-related complication, 99% of them had waist to height ratio more than 0.5, meaning that those patients with BMI 25 to 30 with obesity-related complication, they have obesity. Okay, and we wouldn’t need the waist to height ratio to really declare them or find them or define them as people living with obesity because people who have sleep apnea between and have BMI of 25, I think 30, So they are living with obesity or people with prediabetes or people with osteoarthritis or people with every other obesity complication. So I think we will have to find the right number but if you have a patient between 25 and 30 and obesity related complication, they are living with obesity.

Speaker 1 • 48:55
– Great, yeah, absolutely. So again, just a reminder to look and we find, I guess there was another question in the chat, I’m not exactly sure where if we define obesity as we do with this new overweight category, you know, and waist to height ratio and so on and so forth, this is about two thirds of the population, pretty much. It does increase the prevalence significantly. You show that a further 18% from the enhanced cohort would also be captured. But it’s difficult to access treatment, of course, you know, for such a prevalent disease as you know, it’s certainly in the UK, it’s highly rationed within the NHS, you know, only those with BMIs of 40 plus four out of five complications can get the medication. Either of you would like to comment on this, you know, what is the solution going

Speaker 2 • 49:44
forward as we define more and more people with the disease? I think that the future will be that the medication will be much more cheaper, like the oral, the oral GLP1 will be surely will be much more cheaper. And if you look what happens in the States, the minute the oral GLP-1 was approved, so there is a rise in the using them because they’re much more cheap. So I think we will reach the point that we will have much more, much cheaper medication and we can use it exactly like any other disease, you know, like diabetes, like hypertension, like hyperlipidemia, or any other chronic disease. It’s very expensive in the beginning and then it becomes less and less expensive and we can treat much more people. But we have to really find the people that need the treatment. So first of all, we have to define the disease, we have to define the treatment and then push the stakeholders to really reduce the cost that we could really treat much more people.

Speaker 1 • 50:57
Okay, fantastic, thank you for that. And I think I completely agree that, you know, the landscape is going to change quite rapidly over the next few years. So hopefully we can reach more and more people suffering with or living with obesity. Now, unfortunately, I think Andrea is having some sound problems. So I think she won’t be able to contribute. We’ve got a few minutes left. But there’s a question. I mean, some people do not respond to GLP-1? Do we know why? And what are the options? I think, I mean, in terms of options, like I said, going, looking forward, apart from the medications already approved, of course, we do have other increting therapies, for example, amylin agonists, they’re not still, they’re not, they’re not yet approved for the treatment of obesity, but like I said, you know, there will be other targets, I guess, and of course, triple agonists as well, down the line that may be able to help us. But, Dror, any ideas to why some people don’t respond to GLP-1s?

Speaker 2 • 52:00
Yeah, so I think the reason is that those patients have some sort of monogenic obesity. I have people that we gave them semaglutide, rizepatide, they didn’t lose weight. I sent them to genetic profiling and we found some genetic problems. But I think that’s the reason that we need really treatment that are not GLP-1 based compound, like amylin, for instance, like maybe the glucagon compound with GLP-1 again, but we need treatment that are not GLP-1 based in order to really treat those patients who are not reacting to GLP-1 based compound or cannot tolerate. So there is patients that in the first or second dosage have terrible diarrhea, terrible vomiting, or terrible nausea, and they don’t want to take it anymore. So for those patients, it’s around 10%. We need non-GLP-1 based compound. And I hope we will have a million is the first step.

Speaker 1 • 53:16
– Thank you very much. Yeah. And I think we’re coming up to them, but I think there’s an important, there’s a comment to make. I mean, someone’s raised the fact that obviously weight loss medications can have impact on nutrition. Some patients eat so little, they become malnourished or actually have nutritional deficiencies. And I think-

Speaker 2 • 53:40
– I have a comment on this. This is very interesting. – Yes. – Well, first of all, it’s true. Some patients does not eat because they are so full. And for those patients, we have to reduce the dosage. We have to reduce for those. And a general comment, I don’t believe that only physician treat those patients. We have to use a multidisciplinary team in order to treat people living with obesity. Of course, the physician, of course, physical therapy, exercise specialist, of course, social workers, all this team should treat those patients. For those patients who are not eating, I really decrease the dosage. And of course, a very careful follow-up by the dietician. But a few weeks ago, there was a very interesting publication from Denmark and they measure the food consumption of, apparently in Denmark, they can measure the food consumption by up. And they showed that people who used semaglutide for one year will reduce the amount of calorie that they consume, but also change the institute of the food consumption, meaning they increase the protein, they reduce the simple carbohydrate, they reduce the industry food. Thank you, Dror. Yes, I think it’s really changing.

Speaker 1 • 55:15
The way they people eat. Yeah, absolutely. That’s a really important point. And I’m sorry to stop you there, just because we’ve come to the end of the but absolutely right that we need wraparound care, we shouldn’t just be using these medications, without the important nutrition, physical activity, support and wrap in a wraparound care of the multidisciplinary team. So with that, I’d like to thank everybody for your participation, for asking really interesting questions and apologies if we’ve not been able to answer all of them, but hopefully we we touched on most of them. I’d like to thank my two speakers, you know, Dror and Andrea, for their fantastic talks and I welcome you all to Istanbul in May for EcoConference and of course the updated algorithm for 2026. There will be a feedback form, thank you very much,

Speaker 4 • 56:04
and I wish you all a great day. Thank you. Thank you. Thank you. Thank you.