EASO & WONCA Europe for World Obesity Day Europe 2024: Latest Updates in Obesity Medicines

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Hello everybody and thank you for joining us in this World Obesity Day Yaso Wonka Europe webinar 2024. Today is a very important day because we are celebrating, as I mentioned, the World Obesity Day and it's very important to have in mind that obesity is a progressive chronic relapsing disease which is caused by a very complex network of factors such as genetic, physiologic, biological, psychosocial and of environment but also obesity is a highly stigmatized disease and its stigmatization comes from the oversimplification of obesity as a disease and during many decades was considered a free election of lifestyle and we asked our patients to use their willpower in order to manage the disease. So obesity stigma manifests through social stereotypes at several levels including in schools, at working place and in healthcare settings.

So we structured this webinar in order to explain obesity as a chronic relapsing disease that needs a treatment, a specific treatment according to its causes and biology and also to remove stigmatization. So this webinar was structured in two parts. The first part is about the patient voice and new developments in obesity pharmacotherapy that I will co-chair together with Professor Slomo Vinkel from the Wonka Europe.

I'm Andrea Ciuddin, the Yaso co-chair of the Obesity Management Working Group and I'm also endocrinologist based in Barcelona, Spain. And the second part will be about delivering obesity management and pharmacotherapy guidelines that will be co-chaired by Professor Dickel from Yaso and Professor Slomo Vinkel. So between these two parts we'll have about five minutes break and then we'll come with some details during the break.

Moving to the first part, it's structured in two parts, in two talks. The first one is the patient journey that will be presented by Andrew Healing which is Director of Communication at the European Coalition for People Living with Obesity, ECPO. The second part will be introduced by my co-chair and then we'll have about 10 minutes of Q&A and discussion with the audience.

Please use the Q&A function available in the Zoom. Professor Slomo, please introduce yourself and nice co-chairing this session with you. Thank you, thank you Andrea.

Okay, so dear friends, Wonka Europe is the association of family doctors of European region and we have more than 50 member organizations from 46 countries and more than 100,000 members. One of the goals of Wonka Europe is to strengthen the development of quality work and patient safety and we are committed to cooperate with other scientific organizations and to introduce to our members state-of-the-art updates on topics that are relevant to our daily working as family doctors and general practitioners all around Europe. In this webinar that is held in conjunction with the ISO, we are delighted to continue our series of webinars on relevant clinical topics and scientific updates.

In recent years, highly potent medications have been introduced and the arena of effective pharmacological ways to cope with obesity has been changed dramatically. For example, in my country, in Israel, we are facing a substantial reduction in the rate of bariatric surgery, which reflects the move to pharmacological treatment. It doesn't mean that the overweight and obesity pandemic is behind us.

It is also clear that medications cannot replace education, healthy lifestyle, physical activity and balanced diet. But the landscape of obesity management has been changed and family doctors and general practitioners should have a key role in this revolution. We will learn more other topics today about the ways to choose the appropriate treatment and how to avoid stigmatizing our obese patients.

I want to wish to wish the many participants of this event a fruitful evening and I hope to meet you all again in our future symposium. Thank you. Thank you very much for this introduction.

The European Association for the Study of Obesity promotes person-first language and non-stigmatizing images in all related written and verbal communication. It also actively works to reduce weight bias and weight-based discrimination. So, we thought that the best talk to start this webinar on the World Obesity Day is about the patient journey.

So, Andrew Healing, which is the communication director of ECPO, will explain us lived experience of receiving obesity management impact of latest developments in obesity medication on his and people living with obesity journey challenges that they face. So, Andrew, please, when you are ready, the floor is yours. Thank you, Andrea.

So, as the introduction says, my name is Andrew Healing. I am the director of communications at ECPO and to give you the lived patient experience, I wanted to go way back in time and kind of give you an idea of what it was like for me from a young age, at school age, essentially. So, when I was at primary school, that's when I started to gain weight.

I remember at the time being taken into the nurse's office. My parents were there. I was placed onto a set of scales and I remember the nurse having to push about with levers and sliders to get my weight.

I kind of felt singled out from an early age. None of my other peers were going through this. It was just myself that felt as if I was getting pulled to the side and it was a classic case of I need to eat less and to move more.

That continued all the way through my primary school, so my lower school days, into the secondary school area. That continued. I was later referred to a dietician who was there to try and support me with my eating habits to get my weight under control.

These were sessions that I had to attend on a regular basis. So, it was every couple of weeks I was taken out of school. I had to go to a medical centre and basically speak to a dietician and go through everything that I'd kind of ate for the day.

Myself and I'm sure a lot of other people who are living with obesity can testify to the fact that you don't go through everything that you're eating. You miss points out. You don't give a full understanding of what was there.

So, week after week, I was left feeling as if I was a failure, as if the steps that were putting in place or being put in place for me to follow weren't working because I wasn't working with the process that was there, as they kind of thought. Going through high school in general wasn't the best of times. As somebody who was living with overweight and obesity, I was bullied quite a lot through my teenage years, not only by pupils or peers my age but also with teachers who were the ones who you were supposed to be able to trust when you were at that kind of age.

I remember being in a PE lesson in school and I would always select activities that were off the radar that I could stand away and do. So, I chose to do a gym workout session at this point somewhere where I thought I would be safe, only to be bullied by the teacher that was taking that class and he advised somebody who was standing next to me to watch out the way of the earthquake as I was jumping up and down to warm up. That was something that pushed me towards doing something at that time.

So, I went to my family doctor, a GP who I had seen for a number of years to discuss issues that I had. There were regular appointments with her and we discussed ways of working and what I could do. That worked for a period of time, everything was going okay, my weight stabilised and things were looking good.

It wasn't until slightly later on that things started to change again. Unfortunately, I wasn't able to sustain the steps that were put in place. So, there was a time where I was at an appointment with my GP again who approached the subject of my weight in quite a sympathetic way.

It wasn't being blamed for why I was there, it was more of a concern that she could tell that something wasn't right with the way that I was acting and she asked me to open up to her and I was able to go into the point of it being my weight that was an issue. So, from there, I was referred into a new service that was being created within my health board area. It was a weight management service.

The weight management service was split into a group session. So, there was a group of up to 12 of you who had to sit around a room and discuss the issues that you had. My group that I was in was separated based on the emotional eating factor.

So, it was more of a psychological session than what it would be for a kind of dietetic and food-based system that was there. I went through tier one, didn't really stop gaining weight. So, I didn't think the process was working for me and I dropped out of the group.

There wasn't anything that was keeping me there. My weight continued to gain, continued to be an issue and it was another visit to my family doctor, again, where the conversation came up around my weight and things that could be done to help and support me. She offered referring me back to the weight management service, but at this point, I was really apprehensive.

I felt really guilty at the fact that I had decided to pull out of the sessions before. I felt as if it was my fault. I didn't really deserve to be put back into a place that somebody else could have taken.

It wasn't until that time that I was reassured that there is evidence there that says at the time that it can take multiple sessions, multiple attempts of attending the group sessions before you actually gain from it. So, based on that, I decided to go back on to the service. I started again from the first tier of the weight management service, followed everything that was there, the psychological advice that was there around my emotional and binge eating.

I took that on board and although I wasn't losing a great deal of weight, I was able to maintain the weight that I was currently at. I used the techniques that were there to basically help me get over the emotional and the psychological eating element. I made my way through the different sections.

There was three different tiers in total. There was the psychological tier to begin with. You then went on to a pharmacotherapy type tier.

At the time when this was happening, the medications that were there were very, very limited and the side effects that were with those medications were very severe. Not only did I have the listed side effects with the medication, it also irritated my bowel so I couldn't sustain the medication that was there. Therefore, I moved on to the third tier, which was an extremely low calorie diet.

It was more of a kind of eating less that was there to see if it would kind of kickstart your weight loss. But as we know, that doesn't work. There's only so long that you can maintain such a drastic diet change before you're unable to sustain that and the weight started to gain again.

On this occasion, I was able to complete the sessions that were there. I passed into T4 and I then had surgery where a gastric band was fitted. At that time, I started to lose weight.

I had a very good weight loss with that. I lost 14 stone in total with the gastric band surgery that took place. From the service that was there, I was considered as a success.

I had lost more than 50% of my excess body weight. I was ticking all the right boxes with what I was doing. Everything was great.

Following the surgery, I had two years post-op care. That resulted in monthly appointments where I would go, I would see the service, I would see a dietician, I would be weighed, I would be held accountable for what had happened for that month. Unfortunately, after that two-year period, I was then discharged from the service.

I was classed as a success and I was just left to go on my own. That is where I found that I started to have issues. The weight started to come back and there was nobody to be held accountable to.

It was easy to regain the weight that I had been so successful at losing. It was one of my clinicians who I was still seeing who referred me back on to the weight management service. Unfortunately, they weren't really geared up at that time for somebody who had had the weight loss surgery and who was then regaining.

As a result of that, I was placed back at the start of the weight management service. I was back on tier one. It was very much focused on the same areas as what I had covered before.

I was basically just attending these sessions, gaining nothing from it. However, due to the COVID pandemic, these sessions were cancelled. I was left again to go on my own.

There was nothing there. There was no phone call. There was nothing to check on progress.

Unfortunately, that resulted in further gaining of weight, quite an extreme gaining of weight during the lockdowns that ensued. It wasn't until last year that I had been made aware of further pharmaceutical therapies that were available. They were being released on the NHS, which is the overriding health board for ourselves.

Unfortunately, it's not simple to be able to get that. You have to go through the same weight management processes before that's prescribed. I had no option but to go down the private route.

I made a private appointment with a doctor and I was prescribed one of the medications that are out there. I've done really successfully well on the medications. I was able to lose five stone for the period that I was on them and taking them.

Unfortunately, having to pay for them privately did have a price and I wasn't able to sustain at that time. I had to stop them. That has resulted in a slight weight gain again, but I haven't lost the complete amount that I had managed to get off at that time.

Myself, along with many other people who I talk to and communicate in the patient advocacy area are very much in a similar position where we are looking to see what is available and we will be continuing to try our best on our journey. That's where I'm at just now. Thank you very much for taking the time to listen.

Thank you very much, Andrew, for this beautiful presentation. We'll answer questions in the end during the Q&A session. Thank you.

And now I will introduce Professor Dr. Nick Feiner. His affiliation is that he is an honorary clinical professor at the National Centre for Cardiovascular Prevention and Outcome in UCL, Institute of Cardiovascular Science in London, UK. His B.O. is very, very rich and I could simply summarise it, because we are short of time, that he had more than 200 peer-reviewed papers and more than 23 book chapters along his history.

Dr. Nick, the stage is yours. Shlomo, thank you very much for the introduction and I will just do my best to get the right screen share. Right.

So this is really a very exciting time now, I think, for those of us who have been in the field trying to help people living with obesity to have a more successful and an easier course through their clinical care. We've moved on from, if you like, in obesity treatment, the era of leech bloodletting that persisted for so many years. These are my conflicts of interest.

So I'm going to start off by just really emphasising the point that the effective and, if you like, appropriate care for people living with obesity involves what's now often called medical nutrition therapy. Used to be dietary therapy, but it's more complex than that perhaps now. The issue of physical activity, exercise and reducing sedentariness.

And then the medical treatments of obesity, which may include pharmacotherapy, behavioural therapy, surgery or combinations of those. But all medical therapy should and must include medical nutrition therapy and physical activity approaches. And indeed, all of the data that I will show you on pharmacotherapy in clinical trials, all of these were holistic, comprehensive interventions that were offered to the participants.

Now, we know that greater weight loss leads to greater resolution of the complications of obesity, and it's therefore appropriate that we strive for treatments that will produce greater weight loss, but perhaps even more importantly, can lead to the sustaining of weight that has been lost. If we go back 10 years, pharmacotherapy with lifestyle modification could result in something like four, five, maybe eight, even 10% weight loss at one year. These were, if you like, figures placebo subtracted.

Effective, but probably not effective for many or indeed most of the people who are living with obesity. These were some of the pharmacotherapies that were available at that time. Orlistat, the lipase inhibitor, bupropion naltrexone, a centrally acting combination, and liraglutide, which was at an obesity dose of three milligrams daily, a GLP-1 agonist.

And you can see here that the other way of looking at the success of these medications is by the numbers of people achieving a five, 10 or 15% weight loss. And you'll see that it was a small minority who could lose more than 10 or 15%. And with these medications, there was really nobody who could achieve more than 20 or 25% weight loss.

Now we've moved on and now in 2024, we have medications which will push this efficacy in terms of weight loss further towards the results seen with surgical procedures. And if I show you here now, adding in somaglutide 2.4 milligrams weekly, the obesity dose, and tizepatide 15, or even in some of the studies 20 milligrams weekly, you'll see that with these now something like a half to a third of patients are achieving more than 20% or even more than 25% weight loss. This really is a revolution in weight loss efficacy of these medications.

What's the future going to hold? Well, I think that it's very, we can be optimistic that the combination of these drugs, perhaps with new drugs, is going to lead to even greater weight losses achievable. But I want to make the point that we probably now need to move away from these anthropometric centric outcomes, the loss of weight, the loss of body mass index, changes in waist circumference. And we really ought to be focusing more on the complications, risk reductions, complication improvements, or better still, particularly as drugs increase in efficacy on proper clinical outcomes, mortality, myocardial infarction, stroke, and really importantly, patient reported outcomes, such as quality of life.

Now, I'm going to take a few minutes just to talk about the control of energy balance and body weight, because really, this is central to our understanding of why pharmacotherapy has improved in terms of its efficacy so much over the last decade. We know that food that is ingested goes into the gastrointestinal tract. And from the stomach, our hunger hormone ghrelin is suppressed by food intake.

Gastric distention will also lead to signals of satiety. The stimulation of the pancreas from ingested nutrients results in a number of hormones being secreted, obviously insulin, but also interestingly now a focus on amylin and glucagon. And as food enters the small intestine, we then see the release of hormones, such as GLP-1, gastric inhibitory peptide, polypeptide YY, oxintamodulin, and cholecystokinin.

A second component in the control of energy balance is of course adipose tissue, which itself secretes hormones such as leptin, adiponectin, and this newer one on the block, fibroblast growth factor 21. But we also are beginning to explore how white adipose tissue, essentially a storage tissue, can be converted through beiging and browning into adipose tissue that is thermogenic or wastes or spends energy. We then move on really to the heart of the system that controls energy balance.

We have the hypothalamus where there is, if you like, the homeostatic control of energy balance, but we've learned over the last few years that the brainstem also is a very important site that sends signals into the cortical areas, such as the nucleus accumbens, hippocampus, thalamus, and into things like the prefrontal region, which themselves then connect with the motor cortex, leading to actual behaviors. Now, what these areas do is reflect this complexity of what are the components of energy balance. We have concepts such as fullness in the stomach.

We have potential unwanted effects such as diarrhea and constipation from some of the release of these hormones in the small intestine. I've talked about energy storage and thermogenesis in adipose tissue. In the hypothalamus, where satiety and hunger are sensed and relayed.

The brainstem also does this, but is also probably responsible when stimulated for some of the unwanted effects such as nausea, nausea, and vomiting. But then we get into the complex issues in the cortical regions, reward processing, learning memory, executive control, decision-making, food representation, as well as obviously factors such as smell, sight, auditory, taste of food. All of these are part of the physiology of energy balance.

And what happens is that there is a sequence by which these are signaled predominantly through the brainstem and the hypothalamus into these higher cortical areas, leading to changes in behavior, reflecting physical activity and food intake. So forgive me for that very brief overview, but it's important because control of energy balance is not simple. That's why there are increasing numbers of what are called druggable targets to try and modify this physiology.

I'll start with two rare conditions in which pharmacotherapy has really made a huge advance. Now, leptin deficiency due to mutations in the leptin gene are very, very rare. But the proof of principle here is that if you give leptin replacement to these individuals, you essentially cure them of their obesity and their disordered eating and the other complications of leptin deficiency.

If you study what's happening when you give these children leptin, there are changes in how they detect the salience and rewarding value of food, particularly if they're not eating, they will decrease their attention to food and the rewarding value of food. There are changes which reflect the functional connectivity of the hypothalamus to feeding related areas. And there are actions on neural circuits to diminish food intake.

But at the same time, they diminish the perception of food reward while enhancing response to satiety signals when children like this eat. So this is complex, but it shows you how just this one hormone leptin can have this panoply of effects on eating behaviour. And here you see an example of a child who has been cured by replacing leptin.

Now, slightly less rare, but still rare are mutations in the melanocortin gene and in the melanocortin receptor gene. And now set melanotide is available as a melanocortin agonist indicated for adults and children with Bardet-Biedl syndrome, POMC deficiency, even leptin receptor deficiency. And while slightly less dramatic the effects perhaps than with leptin replacement, there are significant impact on some of these on the weight and some of the complications in these individuals with these mutations, resulting in significant loss of weight and significant reductions in their reported hunger scores.

Okay, so let's now move on to the sort of anti-obesity medications that we would be using in terms of, if you like, these non-single gene mutations. I've mentioned ornistatin, altrexone, bupropion, noraglutide, and fentamintoparamate already, but I'm going to focus on the newer drugs, somaglutide and tizepatide. Somaglutide is a GLP-1 agonist originally developed for treating type 2 diabetes, but at this higher weekly injectable dose of 2.4 milligrams has been evaluated for the control of obesity.

Tizepatide is a dual agonist. It stimulates both GLP-1 and GIP receptors and has also been developed both for diabetes and for the treatment of obesity. I'm going to deal with these a little bit, each one by one.

On this slide, I'll just focus now on the most common adverse events that you see with this treatment, which are predominantly gastrointestinal for both of these drugs, which are in general well tolerated and tend to diminish with time, but in some patients they are severe enough to mean that they do not wish to continue treatment. These side effects can be minimized by very slow and gradual dose escalation and in clinical trials this has often taken three or four months. So as I've mentioned, one is a pure GLP-1 agonist, the other combines GIP activity.

What are the differences? Well, GLP-1 stimulation results in reduction in fat in the liver. The effects on fibrosis are slightly more equivocal. GLP-1 increases satiety.

It can increase nausea. It decreases food intake and this has been shown to be due to the satiety effect, not the nausea. GLP-1 increases insulin secretion.

It decreases glucagon secretion. There is a decrease in gastric emptying, although this doesn't persist with continued treatment. Importantly, GLP-1 receptors are very widespread and we know that GLP-1 receptors in the cardiovascular system result in cardiovascular protection, improved cardiac output and GLP-1 stimulation decreases endothelial dysfunction that is seen with the chronic inflammation of increased adiposity.

GIP has very many similar effects but it differs in that it increases glucagon secretion. So if you're giving both GLP-1 and GIP, you need to balance the glucagon effect so that you don't, if you like, produce hyperglycemia. GIP also decreases gastric acid secretion and it improves insulin sensitivity and lipid storage.

So let's focus first on semaglutide. This, on my schema, is where semaglutide is working. It's given by subcutaneous injection, although there is an oral form available already for treating type 2 diabetes and in development for the treatment of obesity, but not yet available.

Its predominant site of action is on the hypothalamus and on the brain stem. Within the hypothalamus, it increases satiety signals through the POMC-CART system and it inhibits the hunger pathways through the NPY system. But we know that semaglutide also gets into the nucleus of the tractus solitarius in the hindbrain and that this hindbrain activity directly leads to stimulation of areas in the cortex involved with executive control, decision-making, and food representation.

Of course, there are also effects on the pancreas to increase meal-related insulin secretion, its anti-diabetes effect, and also there is an increase in fullness and the unwanted effects on the GI tract of diarrhea and or constipation. So these were the pivotal clinical trials of semaglutide, the STEP trials, and you'll see here that on the first three trials on the left, at one year, the weight losses achieved were in the region of 17 or 18 percent compared to placebo weight losses where they had the same supportive therapy but a placebo for semaglutide of around 3 percent, 4 percent, 5 percent. On the right, STEP 2 is the diabetes trial where semaglutide was given to people living with obesity and type 2 diabetes and in common with all treatments that have been given for treating obesity and type 2 diabetes, weight loss is attenuated but still significantly greater than achieved with diet and behavioral therapy.

If we look at the number of subjects achieving a greater than 15 percent weight loss, these are really why this has been so exciting. In those without type 2 diabetes, more than half of people treated were able to achieve a greater than 15 percent weight loss, something we had not seen before with older drugs. And here is STEP 5, a two-year trial showing that the weight loss is maintained, providing of course that therapy is maintained.

Drugs don't work when you don't take them. These drugs do not cure the physiology, they, if you like, adapt the physiology or they stimulate the physiology back towards a normalization of body weight. So when you stop these drugs, there is a tendency for weight to be regained.

But again, in this trial, you'll see that at two years, more than a third of patients were achieving a greater than 20 percent weight loss. Now the importance I've mentioned of non-weight related outcomes is shown here from the trials looking at cardiovascular effects of semaglutide. The SELECT trial was a cardiovascular outcome trial that exposed over 17,000 subjects to either semaglutide or placebo over a mean duration of follow-up of about three and a half years.

There was a 20 percent reduction in the relative risk of having a major cardiovascular event in those who received semaglutide compared to placebo. In other words, the treatment of semaglutide not only produced weight loss, but it reduced the number of people having a heart attack or cardiovascular mortality. There's been a trial of semaglutide in patients with the specific obesity related heart failure with preserved ejection fracture.

And in this study, there were improvements in the ejection fraction. There were big reductions in symptoms and physical limitations, improvements in exercise capacity and greater weight loss. And a trial in patients with chronic kidney disease and type 2 diabetes was stopped early because the trial monitoring committee found that the reduction in the risk of renal and cardiovascular mortality had been proven early in the trial.

These results have not yet been presented. This is only a headline press release. Now, what about other benefits? A number of the studies in the STEP programme looked at weight related quality of life.

And essentially, what you can see is whether you use a standard weight quality of life questionnaire, the IWCOL, whether you use the more general SF36 or a specific control of eating questionnaire, the use of semaglutide improved all of these parameters. Another important issue, particularly with the amount of weight loss that we're now seeing with these drugs is that the reduction in body fat was greater than with semaglutide than with placebo, and that this was not leading to disproportionate losses of lean body mass. Although I think that that is still a question that needs further exploration.

And you may hear more about that later. Now, one of the other issues that has been raised is whether or not the use of these drugs, either directly or indirectly, through the very large changes in body weight, and we've seen this with the impact of bariatric surgery, might be increasing depression or suicidal ideation. There is a very large study, a post-prescription study, looking at semaglutide versus non-GLP-1 receptor agonist anti-obesity medications.

The study was replicated in people with type 2 diabetes, and this actually found that there was a lower risk for incident and recurrent suicidal ideation in those treated with semaglutide. And the US Food and Drug Administration, who've been looking into the issue of suicidal actions of people on either anti-obesity medications or type 2 diabetes medications, have said that their preliminary evaluation does not suggest a causal link. So I'll move briefly on to tizepatide.

This is a newer compound. There is much less clinical experience than with semaglutide, or that's growing very rapidly. And some of the, if you like, secondary outcomes from their pivotal trials have not yet been fully reported.

So I'm going to deal with this briefly, except to say that apart from the weight loss, many of the reductions in risk factors and so on are very similar to semaglutide and other GLP-1 agonists. There is a large cardiovascular outcome trial underway with tizepatide. It has not yet reported.

So here is tizepatide, its action, and it's very similar, the GLP-1 effects to what I showed you for semaglutide. But the JIP agonist has these effects directly on adipose tissue. Although I think these are not yet well characterized, certainly in human studies.

These are the four pivotal studies, the SEMANT trials, very similar in design to the STEP trials. And what you can see here is that the drug appears to be certainly more efficacious in terms of the amount of weight loss that was seen at one year. You're looking here at between 20 and 25% mean weight losses in SEMANT 1 and 3, 15 to 16% weight losses in those with obesity and diabetes.

And in a weight loss maintenance study where there was an active lead-in, something like a 26% weight loss at two years. So it does appear, although these are not, obviously not head-to-head comparisons, it does appear that tizepatide results in greater weight loss. And a head-to-head trial will be reporting, I think, before long.

So that's where we are at the moment. We have these two new GLP-1 agonists, one a sole agonist, one a co-agonist with JIP. But what we have in the future is this very rich looking development for pharmacotherapy.

The ones that I've put in bold here are drugs which have completed phase one trials and are in phase two trials, or in some cases, even in phase three trials. We have oral GLP-1 receptor agonists. We have combinations with amylin, agrisema, which in its phase two trials exceeded the weight losses with semaglutide alone.

We have GLP-1 glucagon dual agonists, and we even have triagonists. And retatratide just reported extraordinary results in terms of weight loss. There are some other primarily centrally acting drugs in development, but I think what is also interesting is the growth now in interest in the potential for increasing lean body mass by directly impacting on targets such as the methylactamine 2 receptor with demagrimab, purchased now by Eli Lilly, and direct effects on adipose tissue.

So my conclusions are that there is and there will be a growing need for effective pharmacotherapy. And you've heard of the long story from Adrian and how if we had pharmacotherapy that could be used earlier on in the life history of people with obesity, we might prevent many of the difficulties that they face during their life. There are different modes of action and greater weight loss, and this means we're going to be in the position as we are for other chronic diseases like hypertension and diabetes of choosing the right drug for the right patient at the right time.

We're going to learn new strategies for how to use them, single agent, combination, and so on. You'll hear more about that from the guidelines, I believe. I believe we're going to have to change our treatment targets from the current ones, which are really still set in an era where drugs were modestly effective.

5 and 10% weight targets have been smashed. We need to think of weight loss targets higher than that. And if we're going to have stopping rules for people where we judge that the drug hasn't worked, that's going to be difficult because will a 10% weight loss still be regarded as a reason for stopping just because the drug in many people can achieve a 20% weight loss.

But above all, we're going to have to get better acceptance of pharmacotherapy, the need for long-term treatment, and reimbursement. So thank you very much. And with that, I'm going to just say that understanding the factors that drive food consumption, the physiology of obesity, and how energy is spent will allow a deeper understanding and perhaps acceptance of body weight regulation and its abnormalities and how this can be influenced by obesity treatment.

Thank you very much. Thank you. And then now we will move to a few questions that were asked by the audience.

And the first question is related to family medicine, but I will ask you, Andrew. As a family doctor, should I convince my patients to lose weight ever though he or she might feel good in his or her body? Wouldn't it be psychologically ruining for patients' self-esteem and so for psychological wellness? So from my point of view and a number of people that I have spoken to, it's very much a case of not telling somebody that they have to do something because that would be the wrong approach. But having that conversation, asking to have that conversation more importantly than anything.

So as a patient going in to see a GP, if a GP was worried about my weight, if they think that that was causing complications for another illness, I would look for them to ask me if it's okay to speak about my weight, not just going in and saying, your weight's an issue, you need to do something about it. Thank you. Nick, can you? I mean, I absolutely agree, but I think it's something as doctors, we have to learn how to do because I think we tend to be, you know, finger wagging.

We tend to think that we know best. And the reality is particularly, I think, you know, for people living with obesity, they have a life experience and therefore they know what they want, what they're looking for. Our role as a doctor is to be, if you like, their facilitator.

In this regard, there's another interesting question from the audience. And due to the increasing popularity of the body positive movement, do you think that in the future we'll have to change terms like additional weight or obesity, just to help removing stigmatisation? What do you think? Both of you, maybe. I mean, I think it is, it is very difficult, you know, there is no doubt that there is stigma linked to the word obesity.

On the other hand, it is an official international classification of disease, disease names. So I think just renaming something every few years, because it has attracted stigma, is not the right way to go about it. We need to actively reduce the stigma that comes from a lack of understanding about what the disease of obesity is.

Changing the name doesn't do that. Thank you. However, in fatty liver, they did it twice in three years.

Yeah, I mean, we'll see if it sticks or not. Andrew, how do you feel about this? Yeah, so for me, I think it's very much a case of listening to what people are saying. There's been many different terms and terminology that has been changed in the obesity landscape that's there.

So I wouldn't say that it's something that we would never want to do. But from my point of view, from somebody who is a member of a patient organisation, it would be very much a case of listening to our members to see what they think is appropriate. That's what we do now and we will continue to do so.

Thank you. OK, so now let's move to more clinical questions. So I will ask you, Nick, and of course, Andrew, if you know the answers, you can join also.

First of all, what is the place of the role of GLP-1 in patients after post-sleeves, which means after bariatric surgery? And the second is about patients with autonomic neuropathy. Yeah. So we know that bariatric surgery is highly effective, but the degree of weight loss, the degree of disease resolution can vary.

And where clinically it is judged that the impact of bariatric surgery has not been as effective as one had hoped for, it might have been. There are now a number of studies that show adding in a GLP-1 receptor agonist can enhance weight loss and enhance the resolution of risk factors and complications. What's interesting is, and I don't know that we really know this yet, is one of the reasons that the sleeve or even the gastric bypass hasn't been as effective as had been hoped for, because the changes in the gut hormones have not been, if you like, affected as much as we might see in good responders, to use that term.

That may be the case, but there's no doubt that it is becoming a very valuable, if you like, second step after surgery. In terms of autonomic neuropathy, I don't know that I can answer that question. You know, there is this delayed gastric emptying and there has been some concern that anaesthesia induction in patients who are on a GLP-1, that the delayed gastric emptying could cause complications of anaesthesia.

So that it's recommended that, you know, that the GLP-1 should be stopped before any general anaesthetic. The impact on gastric emptying remains, I think, somewhat controversial. Certainly the studies that have been done with loraglodide and somaglotide show there is a reduction, but it's quite transient.

So I think that's the best I can do to answer that. Thank you. We have a lot of questions in the Q&A session.

We have only three minutes left of this first part, but remember that we have another Q&A session in the second part. So please stay with us for the discussion. There are a couple of questions related to the treatment and maybe one of the most important for Nick is, can we predict who will respond to any particular drug? This is the one million question.

Well, my answer to that is no, not yet. There's a lot of work going on. Trying to find, obviously, clinical phenotyping predictors, which are modest in what they can show, they relate to gender, age, duration, but they're quite modest.

To looking at more, if you like, biomarkers, genetics, biochemistry, and so on. There's work going on, but my own feeling is that unless one had a really powerful blood test to do to predict, the reality is, like for hypertension, we give our medication, we assess the response, and based on that response, we decide whether we're giving the right treatment or not. I think it's going to be like that for quite a long time to come.

Thank you. I'm not a doctor by degree, I don't know. I think that some of the questions we can move to the next part, because they are mainly clinical.

I don't think it's a question, rather a remark. How to stop ozempic history in the whole world? I think that there is no way to stop it. I think we agree.

I'll very quickly just say something. One is, it is indicated for treatment of obesity. It is not indicated to be misused as a cosmetic treatment for people who do not have obesity.

I can't stop the abuse, the manufacturers can't stop the abuse. Abuse occurs with many other drugs. The second thing is that once the hip replacement was invented, there were millions of people who were eligible, and the resources were not there to give them their hips.

Over the succeeding decades, we increased the resources to make hip replacements more available. That's what we need to do with pharmacotherapy for obesity, in my view. Yes, if I may comment, because it's a very burning question.

I think that we don't know what is the effect of GLP-1 replacement in a very healthy person. We can hypothesize that if you give such a high level of GLP-1 in a healthy system, you can cause damage, or you can change the setup of hunger and satiety. I think if we will find such a study or proof that if you give such a high amount of GLP-1 to a perfectly healthy system, you may harm the patient.

Then we can stop this misuse of GLP-1 in healthy persons. Thank you. I think that for the interest of time, we have to move to the break.

We'll have five minutes break, and then, as Professor Vinker told, we'll try to address the rest of the questions in the second part, because they are more related to drugs. So, see you after the five minutes break, and please try to use these five minutes to quickly answer a survey that you soon have on screen, the code. It's a short survey just to the assessment of healthcare professional perceptions and approaches to obesity in clinical settings, and see you after the break.

Thank you. Okay, so I hope that you enjoyed the break, and all of you filled the questionnaire with the link that we gave you, and now we are moving to the next part of our session, and it's my pleasure to introduce to you my good friend, Professor Dor Vinker, that will share this part with me and will give the first lecture. So, Professor Vinker is the Chair of EASO Collaborating Centers for Obesity Management, COMS Network, and Lead of COO for Adult Patients with Obesity Base at the Hasharon Hospital, Rabin Medical Center in Israel.

He is the Chair of the EASO COMS Network, leads a comprehensive care facility for adult patients with obesity at his hospital, Hasharon, Rabin Medical Center in Israel, and is the Head of Internal Medicine Department at the Obesity Clinic, and is also an Associate Professor of Internal Medicine at the Tel Aviv Medical School, University of Tel Aviv in Israel. So, Dr. Vinker, the stage is yours. Thank you, Professor Vinker.

Just before I will start my talk, I will a few words on EASO. EASO is the leading voice of obesity science, medicine, and community in Europe. So, we represent scientists, obesity specialists, physicians, healthcare practitioners, and public health practitioners.

We established in 1986, and EASO is the Federation of Professional Membership Association from 36 countries. So, my talk will bring a few cases that I treated and try to really learn from them. So, this is my disclosures.

And I want to ask ourselves, how do you optimize or how we optimize patient care? So, I will start with the first patient, Noah. She's 27 years old. Her BMI is 35.

And she had a gunshot wound three years ago. And she went through a highly selective vagotomy. And since then, she really gained 21 kilos.

Her obesity risk factors are carbohydrate craving, sleep disturbances, which is very understandable, stress, and she's taking metoprolol due to very rapid heartbeat. Now, before I will start to show you how we treated her, I want to just go briefly on the mechanisms that Professor Finner showed us before. And we clearly see that all these hormones that comes from the adipose tissue and from the gut, really activate the satiety nucleus and inhibit NPY-agglutinated hunger nucleus.

But we also see that the vagal nerve has effect on the nucleus solitary struct and the arapostrema. And if we look on this cartoon, we can clearly see the effect of the vagus nerve beyond all the satiety from the adipose tissue and GLP-1 and gurlin. Now, if we look on people with obesity, we see that in the baseline, people with obesity, when we compare them to lean patients, they have lower GLP-1, PYY, and higher gurlin.

And this is a physiological malfunction in people with obesity that caused them to be more hungry alongside. People with obesity, when you show them food cues and you make fMRI, functional MRI, you can see enhancement in the amygdala and insula comparing to lean patients. And people with obesity have metabolic adaptation when they are losing weight.

All these mechanisms cause weight gain or very difficult difficulty to lose weight. Now, if we go back to Noah, we can see that she took metoprolol and we know that beta blockers can cause weight gain. So we stopped metoprolol.

Then we gave her a Mediterranean low-carbohydrate diet, which is the best diet in the Mediterranean. We advised her to do three hours per week for physical activity, and we treat her with biofeedback to improve her sleep disturbances. She already had psychological treatment due to the post-traumatic stress disorder.

Now, if we want to treat her pharmacologically, we look into these studies that tried to phenotype the treatment of obesity. And I think this is a very interesting and important first step to try phenotyping the treatment of people with obesity. And in this study, Acosta divided people with obesity to four groups.

The first group is emotional hunger. And for this, they advised us to treat with naltrexone bupropion. The second group is hungry brain.

And for this group, they advised us to treat with phentermine and topiramate. The third group is hungry gut. And for this, they advised us to treat with GLP-1, in this case, the raglutite.

And the fourth group is slow burners. And for this group, they advised us to treat with phentermine. And they showed in their study that if you phenotyping the patient, according to this system, you can enhance the weight loss through the phenotyping of the treatment.

Now, if you recall, Noah went to highly selective vagotomy, means that the cues and the signals from her stomach to the brain, to the nucleus, through the vagal nerve is damaged. And we thought that if we will give her the raglutite 3.0 milligram, we can replace partially the GLP-1 activation in the nucleus oratory tract due to the activation of the vagal nerve. So we started to treat her with liraglutite 3.0 milligram.

And indeed, after one and a half year, she lost 70 kilogram, nearly all the 21 kilogram she gained. Now, as we saw very, very frequently, after one and a half years, she came back and she said the same sentence that I'm hearing all the time, the drug stopped work, meaning I gained seven kilogram and the craving for carbohydrate coming back. So this sentence is very, very frustrating because we have to deal with patients that succeeded to lose weight.

And now under the same circumstances with physical activity, with diet, with liraglutite, they are gaining weight. So let's see if the drug really stopped working. So for this, I will show the scale IBT study in which they compare intensive behavior treatment, 21 counseling visits, combining liraglutite with IBT and make multi-component, meaning combining diet, liraglutite, and IBT.

And we can see that the multi-component and the IBT liraglutite was comparable in the end of the year. Now, sub-study of this study is very interesting because when they compared three groups related to the hunger and craving frequency, we can clearly see that liraglutite and IBT was much more effective than other groups reducing hunger and craving. But this effect was diminished after 26 weeks and after nearly 40 weeks, meaning that after 26 weeks, all the groups had the same craving frequency.

And after nearly 40 weeks, all the group had the same hunger cue. Now let's do some exercise and put the weight loss results on this graph. And now we can see that when the craving frequency was equal, they stopped losing weight, but still the drug worked because it's prevent the weight gain, meaning the first part of the first function of the drug, of the GLP-1 is causing weight loss, but the more important part is keeping the weight off, meaning maintain the weight loss.

Now, it's very interesting why if you have the same craving as the beginning or as the placebo, you still maintain the weight loss. And this is a question that we don't know yet. Now, if we combine liraglutite with physical activity, we still maintain the weight loss.

And in this study, they lost by lifestyle around 12%. And then they had placebo, physical activity, very intense physical activity, liraglutite and combination of liraglutite and physical activity. And we can clearly see the combination of liraglutite and physical activity make maintenance very, very effective and even enhance the weight loss nearly 16%.

So we can maintain the weight loss by combination of lifestyle, physical activity, changing diet and GLP-1 analog. So we have to convey the message that the drug didn't stop working. It's now changed the works and maintain the weight loss.

Now we can see the same results in the step five. Now it's two year study with semaglutite 2.4 milligram. Again, very impressive weight loss and maintaining the weight loss as long as you take the medication.

And in this study, they also measure the craving around the two years. And we can see that if you measure the control of craving, it's still there after two years. If you measure the craving for savoury, it's still there after two years.

But if you measure the craving for sweets, it's diminished after two years. And this may lead to reduction of the mood effect, meaning that people, mainly women coming to us and say the drug stopped working, maybe they are relating to the feeling of craving of sweets, but the drug is still working. Again, if we look on the measurement of hunger and fullness, we can see the effect of the semaglutite.

Here it's until the first year, but after the first year, it's comparable with the placebo reduction of hunger and stabilization and increased fullness and stabilization. Now we do the same exercise and we put the weight loss effect. We clearly see the same phenomena.

When you have diminished the fullness feeling, you reduce the weight loss, but you maintain the weight loss. So if we want to say now the drug has two components, the first component is weight loss, but the more important component, the only thing that can maintain the weight loss is using the drug with lifestyle. So we have to convey the message is that the patients must keep on taking the medication because now the medication can prevent the weight gain.

So we have to review the history of the patient. We have to encourage physical activity and to do physical examination. We have to really see the social situation of the patient.

We have to discuss with them on the targets and what they are prefer, what their preference, if they want to have a operation, bariatric surgery or medication or just lifestyle. And we have to set a goal. The second cases I want to relate on the issue of obesity in the elderly.

So we have four cases. The first one is elderly woman, age 68 with BMI 31 and type 2 diabetes. The second one is elderly man, 72 years old, BMI 33 and osteoarthritis.

The third one is elderly man, age 80, BMI 32 and mild hypertension. And the fourth is elderly woman, 70 years old, BMI 35, low back pain and sleep apnea. So now we see in this huge study coming from the UK that the relation between mortality and obesity is diminished when you become older.

If you look on the line, on the curve of 80 years and above, in BMI 30, the risk is one. So there is an increased risk of mortality if you are 80 years old and your BMI is 30. So we have to think a little bit differently in this area of ages.

What we know is that in the elderly ages, we can clearly see that there is sarcopenic obesity, meaning that especially men reducing the muscle and especially women increasing the fat. And this leads to sarcopenic obesity, meaning obesity around the visceral adipose tissue, increasing the visceral adipose tissue and losing fat-free mass. And this is very, very bothersome.

And this is very dangerous for those elderly obese patients. And we can see that again in the elderly obesity, in the elderly, there is reduction in muscle mass, there is increase in fat mass that leads to increased risk of fracture and increased risk of cardiometabolic risk. And very recently, we published this ESPEN-ESO consensus statement on sarcopenic obesity definition.

We have to screen for this. If the BMI is above 30 and there is suspicion of sarcopenia, then we have to have a diagnosis that is based on two steps. The first step is measuring the muscle function.

And the second step is measuring the body composition. And then we have stage one, stage two. Stage one is no complication.

And stage two is the presence of sarcopenic obesity with complication. Now, we know that this sarcopenic obesity in the elderly can really increase the basic activity of daily living danger. And in the other hand, we can clearly see that if we can lead to a weight loss of 7.5% in those elderly, we can prevent nearly 30% of knee replacement surgery, meaning that weight loss in those elderly obese patients can really improve their health.

Now, there isn't many studies that examine the effect of pharmacotherapy on elderly obesity. One of the important one is from Perna that really took women, the type two diabetic women, and the duration of diabetes between three to seven years, BMI of 32, mean age of 68. They were treated by metformin and liraglutide, and with diet between 1,800 kilocalories to 2,500 kilocalories per day.

And what they showed us are very important results. They showed us that treating those women with the liraglutide can reduce body weight, but didn't reduce considerably fat-free mass, meaning that reducing the weight of those women did not lead to sarcopenia. Another issue is that if you measure the level of GLP-1 in elderly obese, and this study showed this, if you measure it in a part of six years, so you can see that the baseline GLP-1 is lower in these obese patients, as I showed you before, but after six years, it's even lower, meaning as you become older and older, your GLP-1 level is reducing.

Now the GLP-1 is very important for muscle health, and in this study from animal, we can see that if you take a mouse leg and you denervated it, and you denervated it after you gave liraglutide to the muscle, so liraglutide can really preserve the muscle function and muscle anatomy. So this is the control, this is the denervation on the muscle of the mouse, and this is the muscle with liraglutide and denervation. So liraglutide or GLP-1 can really protect the muscle from denervation or from harm, and even from steroids-induced myopathy, they showed us that GLP-1 can really protect.

So in order to really see if semaglutide 2.4 milligram have difference in weight loss according to age and have a different fat-free mass loss than fat mass, we measure in this subgroup analysis the effect of weight loss according to age and the effect on fat mass and fat-free mass, and what we showed in this abstract that the weight loss is comparable according to the age and there wasn't difference between below 40, between 40 to 60, and above 60 regarding the weight loss. When we measure the fat mass and the fat-free mass according to below 50 and above 50, we showed that above 50 the ratio between fat mass loss and fat-free mass loss was still a positive ratio, meaning that people above the age of 50 that were treated by semaglutide 2.4 milligram lost much more fat than fat-free mass, and I think these results can really demonstrate that treating GLP-1 in the age above 50 is really profitable and really reducing more fat than fat-free mass. Regarding the side effects, there wasn't difference between the ages.

Now if we want to really summarize the algorithm, here is one of algorithm that was put in the literature by Asaf Book, and they advise us to treat first in physical exercise and enrich the diet with protein, and if we don't reach the target of weight loss, then we can add GLP-1 to the lifestyle changes, and if we don't reach the target of weight loss in those age group, then we can offer a metabolic barotrauma surgery to these elderly obese patients. So if we look on the targets of treating obesity, so we have weight loss as the first target, we have maintenance of the weight loss as the second target, and the third target is the prevention of treating the disease. So this is, I think, the algorithm that we are going from one to three in the younger group, but I want to suggest that in the elderly group, we have to do it opposite.

We have to look what are the risk factors and then go to the target of weight loss, and I want to finish with this suggestion of treating those case studies. So in the case, the first case, the elderly woman, age 68 years, BMI 31 with type 2 diabetes, of course we have to offer her lifestyle modification with GLP-1 receptor analog or Olestat. The second case, in the elderly man, 70 years old, BMI 33 and osteoarthritis, we can offer them lifestyle modification with GLP-1 analog, and we are very eager to see the results of step nine that will show us what will happen in the treatment of osteoarthritis with GLP-1.

The third case is the elderly man, age 80 years old, 32 BMI, mild hypertension. So he's 80 years old, BMI of 30, 32. I think in this case, we can treat him with lifestyle modification.

I don't see the reason to reduce his weight more. Now in the fourth case, the elderly woman, age 74, BMI 35 with low back pain, sleep apnea. Again, we can offer her lifestyle modification with GLP-1 because we know that GLP-1 can improve sleep apnea.

And I want to finish the talk by summarize that treatment strategy should be really multidisciplinary and we should treat people with obesity in multidisciplinary centers to offer them all the options to treat obesity. Thank you very much. Thank you, Dror, and because we are running out of time, we will move directly to our last speaker.

And I hope that we will have some time at the end for some questions from the audience. So I would like to introduce the next speaker. And she's the chair of MoCA Special Interest Group on Noncommunicable Diseases, a professor in family medicine at the Universitat Catholica San Antonio and general practitioner in Murcia, Spain.

She has been a dedicated family physician since 2005, specializing in diabetes management. She contributes significantly to diabetes research as a member of several groups focused on primary care and diabetes management. With over 50 communications presented at national and international congresses, including three awards and numerous publications in the STEAM journal, she is recognized for her expertise and contribution in the field of family medicine and diabetes management.

The stage is yours. Thank you. Thank you very much for the presentation.

And it's a pleasure for me just to share with my colleagues this Obesity World Day learning. I was taking my notes because it's very important just for us as primary care physicians have clinical guidelines, simple tools just to use pharmacotherapies for obesity management. So here is the picture of the World Obesity Atlas 2023 report.

And here we have the data. I showed you the data from Spain, a Mediterranean country, Mediterranean food. And here you can see in the left side of the slide, the projected trends in prevalence of obesity for from 2020 to 2035.

And as you can see here, it is going to increase in men, women, boys and girls. And the prevention for obesity, the prevalence for obesity in 2035 in Spain is going to be 37% in this year. So we have a problem.

We have to give solutions for our patients, for our patients, because it is going to increase the prevalence of obesity is going to increase the prevalence of overweight. And it's going to increase the health care cost, the premature death and all the issues associated. So family doctors will play a crucial role in managing obesity and improving the health and well-being of the patient with obesity.

So clinical guidelines for the use of pharmacotherapies in obesity offer valuable strategies for us as family doctors to manage obesity. These guidelines typically encompass evidence-based recommendations for the prescription and monitoring of medications. But I think we have many guidelines, but we need simple tools.

We need to be simple, maybe with the collaboration of family physicians and be practical for medical, for primary care management. So the first question I would ask to me is just what do we need from a guideline? And I think we need just the assessment for patient assessment. So before prescribing pharmacotherapy, we need a comprehensive assessment for the patient, medical history, comorbidities and all that is important for the assessment for the patient.

We need to have the very, very, very, very keep in mind the treatment goals and establish these goals with the patients, not only the target in weight loss, but also in other metabolic parameters and reduce the comorbidities. It's important also that we address the selection of the pharmacotherapy and also when combine this therapy. Very important the monitoring and follow-up.

We need also formation and information education in lifestyle modification. It's very important just to educate the patients and give them support. And of course, we need a multidisciplinary approach, consider involving a multidisciplinary team, including the physicians, psychologists, exercise specialists to provide this comprehensive care for patients with obesity.

So I think I am very ambitious, but that is the eight points I need from a guideline. Here, I present you the guidelines we have now. Until now, I'm not talking about all these guidelines, but it's very important just to keep in mind from others.

We have these guidelines in clinical management of obesity. We have also specific guidelines in pharmacological management of obesity. And we have also in adults obesity-related complications and comorbidities.

And we are going to talk, I am going to talk at the end of my presentation about one comorbidity that impacts a lot in obesity, such as diabetes. And we have also guidelines in obesity and bariatric surgery. So the first guideline I would like to comment is this one, is the National Institute for Health and Care Excellence, the UK guidelines, the UK guidelines, obesity identification, assessment and management in adults.

It's a very valuable guideline with the recommendation that give us recommendations on principles of care, identifying and assessing overweight, obesity and central adiposity. Of course, assessment, lifestyle, behavioural, dietary and pharmacological interventions give us also some points about physical activity and also bariatric surgery. This guideline gives us this table with the medication that have approved at that moment in 2015 with the, sorry, 2023, with the starting criteria and stopping criteria for early start, liraglutide 3mg and semaglutide 2.4mg, when to start and when to stop these medications.

The next guideline I would like to comment is our guideline, our European Association for the Study of Obesity, guideline 2015, with the recommendation in definition and classification of obesity, clinical evaluation of obesity, comprehensive management and plan for obesity and with specific components of treatment in nutrition and diet, physical activity, psychological support, pharmacological treatment, bariatric and metabolic surgery and treatment of complications. That is very important. This guideline gives us this important table with the BMI and also the waist circumference and comorbidities and when to treat only with lifestyle intervention and when to treat with lifestyle intervention and also with drugs, as you can see here in the table.

I find this algorithm very useful because in the first step the ESO give us the, we have to do, determine, determine degree of overweight and obesity after we must assess our patients about comorbidities, lifestyle, eating behaviour, ETC. We must set goals and finally we should manage obesity for these patients and it's a step algorithm for assessment and treatment of our patients and it's very useful, yes, they manage with loss, with nutrition, physical activity, cognitive behavioural therapy and when to treat with the medication available at this 2015. Give us also the summary of recommendation in nutrition and dieting, physical activity, cognitive behavioural therapy and when to treat with pharmacological treatment.

It is said that it's recommended for patients with BMI more than 30 or BMI more than 27 with an obesity related disease and the efficacy pharmacotherapy should be evaluated after the three months and we have to continue monitoring our patients. The next guideline I would like to comment is this one, is the European Practical and Patient-Centred Guidelines for Adult Obesity Management in Primary Care 2019 with the recommendations in communications in adult obesity management, clinical evaluation, obesity treatment and comprehensive adult obesity management in general practice that is very useful for us as primary care physicians and I find this overview very, very interesting because it divides the two situations into two situations if the patient comes to our consultations to treat body weight issue what we have to do and if the patient comes to our clinic for another issue the first step we have to do is ask the patient for permission to speak about weight and of course avoid any stigmatisation so it's very important just to treat if the patient comes to treat the body weight but it's very important also just to have this in mind because there are many patients at least in my clinic here in Spain in Cartagena Murcia Spain where I have my clinic the patient usually comes for another issue and I have to ask if we can we can speak about the weight. So they have also this guideline give us important points to ensure successful treatment for obesity with the recommendation avoiding stigmatisation using motivational interviewing that is now a little bit discussed, improving knowledge, adherence to treatment, motivation to change and quality of life, investigating psychological aspect and I'm going to the last point here treatment could be considered a successful success if a patient with obesity has changed lifestyle in the long term, improved body composition, decreased comorbidities or still metabolically healthy.

So that is very important it's not we are not talking about just the weight loss we are talking more than that and also the European practical and patient centre guidelines give us key practical message for the management of adult obesity with this recommendation in discuss the patient the patient's personal situation, the degree of motivation, evaluate the patient understanding and identify the potential barriers that they have to achieve the goals and all these points that are very very interesting. So the other guideline I use like to comment is this one the endocrine society European society of endocrinology and also the obesity society 2015 in pharmacological management of obesity and endocrine society clinical practice guideline that give us recommendations in care of the patient with overweight or obesity, alternative drugs at that moment in 2015 and off-label drugs not recommended. So the first recommendation they give is diet exercise and behavioural motivation should be included in all obesity management approach for BMI more than 25.

Patients who have a history of being unstable to successful lose and maintain weight on whom mid-level indication are candidates for weight loss medications and finally they say that to promote long-term weight maintenance suggest the use of weight loss medications for that patients with a BMI more than 30 or BMI more than 27 and one more than one associated comorbidity. It's very interesting in this guideline when to start therapy considerations for complications and when to discontinuing therapy and very important just to avoid therapeutic inertia and reassess and evaluate every three months to all our patients. This table is from the guideline from this guideline with the drug the advance of this advance of the drugs approved at that moment in 2015 that Fentanylmine, Fentanylmine, Topiramide, Longcarcerine, Orlistat, Naltrexone, Ropion and Liraglutide three milligrams.

Now I am moving to the American Association of Clinical Endocrinologists and American College of Endocrinology and I am going to move to the two latest guidelines that I would like to comment in the the chapter of comorbidities and this guideline is addressing bias weight stigma in medical care of patients with obesity and clinical practice guidelines for type 2 diabetes management. In this guideline 2023 the key recommendations is obesity as a chronic disease emergence of new adiposity based chronic disease diagnosis reducing weight bias and stigma that is I think is very clear in the new guidelines the impact of weight bias and stigma on patient with obesity and mitigation strategies is very important just to treat ABCD as a chronic disease model as we we treat all the chronic disease all the chronic diseases and it's very important diagnosing adiposity based chronic disease and give our patient evident based treatment recommendations. Here we have this important this I think I think is very useful this table with the with the medications hemagglutide, liraglutide, fentermine, topiramate, lantrexone, the combination with naltrexone, propion, orlistat or fentermine, the class in class weight loss, the potency in weight loss, the mechanism of action, delivery system, the starting dose, also the treatment dose, the potential side effects, cautions and contraindications and also is important just we have here also the access for the patients or the cost of medication or the systems national systems.

In this consensus this consensus give us also the recommendations in addressing stigma and bias the complication centric model for the care of person with overweight or obesity and also the recommendations in considered pharmacotherapy for weight loss when lifestyle measures alone are inadequate to achieve weight loss in those with ABCD. The FDA approved agents shown to have efficacy to achieve weight loss goals that impact prediabetes including hemagglutide 2.4, liraglutide 3 milligrams and fentermine, topiramide extended release and the final point they gave us is weight loss medication should be considered to help individuals with a BMI of 27 to 30 and type 2 diabetes or at least one ABCD complication and as well as all individuals with a BMI more than 30. So we have many patients in this in this case and we have to address to our patient just to help them to treat and manage obesity.

This is the last guideline I would like to comment and that is the people of diabetes I say that this American Diabetes Association the standard of care 2023 and here this guideline is very is very useful we have many chapters with the prevention and strategy just to prevention or the light type to diabetes and their comorbidities the with therapeutics approach that can reduce complications mitigate cardiovascular risk and improve health outcomes. They gave us this table when to treat with diet physical activity and behavioral therapy in all patients with diabetes more than 25 BMI and we must treat with pharmacotherapy at those patients with type 2 diabetes and BMI more than 27. Here is the main algorithm for the use of lowering medications in the management of type 2 diabetes here is is the algorithm for treating type 2 diabetes and as you can see here in the algorithm there is a special a special box just to achieve and maintain off weight management goals and it is said here that general lifestyle advice with medical nutrition therapy eating patterns physical activity and also intensive evidence based structure weight management program consider medication for weight loss and consider metabolic surgery and when we choose for treat patients with type 2 diabetes where where in which our main goal is just to reduce or maintain the weight here we have the recommendations with medications in efficacy for weight loss very high semaglutide or trisepatide high dulaglutide and liraglutide intermediate GLP another GLP receptor agonist not the least above and also a GLT2 inhibitors.

In in this guideline the American Diabetes Association have many chapters but it have in a specific chapter in on obesity and weight management for prevention and treatment of type 2 diabetes in the in the last in the last update in 2024 this year and here we have the recommendations use pens a person-centered non-use non-judgmental language and avoid the the stigma for for the in the language for treat people with obesity and we have I have put here the the this box with the with our recommendations in people with type 2 diabetes and overweight or obesity weight management should represent a primary goal of treatment along with glycemic management and people with diabetes and overweight or obesity may benefit from from any magnitude of weight loss weight loss of three to seven percent of white lines of baseline improves glycemic and other intermediate cardiovascular risk factors so for a American Diabetes Association is very important to treat overweight and obesity in type 2 diabetes as is said in the guideline. Finally we have the medication in the ADA standard of care in diabetes short-term treatment medication less than 12 weeks here we have fentanyl we have also long-term treatment with Orlistat fentanyl the combination of fentanyl with topiramide with topiramide rupropion also liraglutide and semaglutide antisepatide in the last update in 2024 but it's very I I'm not going further in the common side effects and the and the mechanism that is said before by the professor Finner. So summary of the recommendation in the guidelines here I put this table with a measure of obesity diet or lifestyle and pharmacotherapy when it's indicated and I think we can find very common points in all the guidelines that I have commented.

And finally in summary we as primary care physicians we play a key role in management of obesity we have many guidelines I bring here a little bit but it is clear that we need this guideline with multidisciplinary approach with a multidisciplinary team where mainly with the collaboration with another specialities but also with the collaboration with primary care physician because we need practical recommendations for pharmacological management of obesity. Thank you very much. Thank you very much Anna and we are very short of time so I will see I think that we'll ask one or two questions from the audience and then we will make a short round of take-home messages for all our lecturers so let's start with.

I see there is a question here Anna for you so do you have any simple guidelines for primary care physician in Spain? Okay we have no very simple but we have a guidelines today we have presented zero guidelines that is signed by 14 societies involving all the multidisciplinary approach endocrinologists, primary care societies all sign this guideline I have another opportunity it's not it's not a simple tool because it's very huge with nearly 200 pages but I think it's very useful more than we have also some recommendation but I feel that we need more education for our patient and we need also more education to our colleagues just to address obesity and treat that specifically in our clinics. Absolutely agree I just want to comment that we are trying to go out of the BMI meaning that we have to find a way to treat the patient not according the BMI but according to the complication like the ADA ASD meaning that we know that we have the select now so people with obesity that have cardiovascular disease according to the study of the select should be treated with semaglutide so we have to go to the point that we will treat the patient according to phenotyping them and according to the complication. Thank you and now a question to you Nick and to Duol there are several questions in the era of sarcopenia the need for a protein support problems with micronutrients with GLP-1 treatment so try to address those concerns.

So please Nick please. Well I just can say I mean of course we know that many people living with obesity have a poor quality diet and that's why medical nutrition support is indicated I think for everybody it's a matter not just of saying you know eat less it's a matter of improving the quality of the diet and that will hopefully address the issue of many of the micronutrients or even protein not deficiency but low protein intakes that you see in many people living with obesity I mean vitamin and nutritional deficiency are there at baseline. With surgery of course we expect to assess these at baseline and monitor them I think if we're moving into the era of pharmacotherapies producing 20-25% weight loss we'll have to consider the same approach for pharmacotherapy.

Absolutely that's what I want to say that we will have sarcopenia and we see sarcopenia now with this tremendous effect of the new pharmacotherapy that will lead to 20-25-30% weight loss this is the bariatric metabolic bariatric surgery area and we will have to really encourage people to use micronutrient and to use a protein and to measure the muscle quality and strength because this such amount of weight loss is really becoming very dangerous so we have to really adjust to such a huge amount of weight loss and really to do all our efforts to advise on micronutrients supplementation. And of course one of the challenges is that of course not all of the patients that we see who are living with obesity need a 20 or 25 weight loss and that's where I think guidelines are going to have to evolve to take it that's where the BMI will come into place if you like as to what dose or what the degree of weight loss is indicated you know we've been used to having such poor drugs that we've put our foot right down on the accelerator pedal to try and get the maximum effect we may not need to do that with the newer drugs. Yeah okay so I think that we are getting really near to the end of this webinar so one or two sentences of take-home messages from all of you so and we'll start with Anna you're the first on my screen.

My sentence is very clear we primary care physicians play a crucial role and we need simple tools we need a medical education to give to our patients and simple tools just using our consultations. Thank you and second next is Nick. So we're in a new era of effective and safe pharmacotherapies we all need to learn how to use them and we need to learn how to use them responsibly but we should be delighted and ecstatic that after all these years of positions we have got something to add to our armamentarium for helping our patients.

Thank you and Dror. I think obesity and obesity disease is a huge global problem to fight this huge global problem we have to really cooperate all the healthcare professionals and we have to have multidisciplinary team to treat patients with obesity chronically and for lifelong and for this we have to really combine all our forces in order to really tackle this huge epidemic. Okay so thank you all I think it was a very interesting webinar.

Please feel the evaluation form that we will put in. Okay so thank you and I hope that we will continue to cooperate not the next day obesity day but during the year as well. So good evening to everybody.

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