As current understandings of obesity (ie, a chronic disease requiring long-term management) are adopted across the world, screening and treatment can no longer follow a one-size-fits-all approach. Listen in as 3 global experts in obesity medicine highlight the emerging evidence from recent conferences that are changing real-world practice today. Learn how the latest findings apply to specific patient populations and why healthcare professionals should individualize treatment based on patient preferences and relevant risk factors.
As current understandings of obesity (ie, a chronic disease requiring long-term management) are adopted across the world, screening and treatment can no longer follow a one-size-fits-all approach. Listen in as 3 global experts in obesity medicine highlight the emerging evidence from recent conferences that are changing real-world practice today. Learn how the latest findings apply to specific patient populations across the United States, Europe, and Asia as well as why healthcare professionals should individualize treatment based on patient preferences and relevant risk factors.
Presenters:
Stephano Del Prato, MD
Professor Emeritus of Endocrinology
University of Pisa
Pisa, Italy
Soo Lim, MD, PhD
Professor of Medicine
Department of Internal Medicine
Seoul National University College of Medicine and Seoul National University Bundang Hospital
Seoul, South Korea
Donna H. Ryan, MD
Professor Emerita
Pennington Biomedical Research Center
Louisiana State University
New Orleans, Louisiana
Link to full program:
https://bit.ly/4pwFhEo
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This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Speaker: We are recording. Get started when you are ready.
Dr. Donna Ryan (Pennington Biomedical Research Center): Welcome, everyone. I am Dr. Donna Ryan, and I am Professor Emerita at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. That is a research division of Louisiana State University.
I am so fortunate today to be here with two of my colleagues from around the world. I have Dr. Soo Lim from Seoul, South Korea. Soo, tell us about yourself and tell us about your university.
Dr. Soo Lim (Seoul National University College of Medicine): Thank you, Donna. It is a great pleasure to join you and Professor Del Prado. I am Soo Lim, Professor of Medicine at Seoul National University College of Medicine in South Korea. My clinical and research work focuses on obesity and type 2 diabetes.
Dr. Ryan: Excellent. Stefano Del Prato, my colleague from Pisa, Italy. Professor Del Prado, tell us about yourself.
Dr. Stefano Del Prato (University of Pisa): Yes. Thank you very much, Donna. It is also a great pleasure for me to be able to join you here in this discussion. I am a Diabetologist. I am currently a Professor Emeritus at the University of Pisa, where I have been the chief of the local diabetes unit, and I have been working for 40-plus years on type 2 diabetes, pathophysiology of the disease and the current treatment and possibly future treatment as well. Related to that, of course, dealing with type 2 diabetes, also some work in obesity.
Dr. Ryan: The amazing thing that is happening is that our diabetes organizations have embraced obesity and they are giving a run for the money to our obesity organizations. There is just so much research that is coming out of our diabetes organizations. Would you agree?
Dr. Del Prato: Yes, definitely. We have been predicating years and years over the past decades that obesity was a main cause and a main driving force for the increase in the prevalence and the epidemiology of diabetes. Yet we had very limited weapons to really fight it.
Actually, if you remember, I am old enough and some of you may also remember, that when we were treating people with type 2 diabetes, we were concerned because the treatment that we had at that time was a treatment that often was associated with body weight increase. It has been really struggling over the years to try to find something.
We are going through a revolution now and we are talking more and more about obesity because, fortunately, we do have now more powerful and more appropriate form of treatment for this condition, including obesity as a disease by itself and associated type 2 diabetes and all the other comorbidities that often are associated with obesity.
Dr. Ryan: Absolutely. One of the most amazing things that is happening is the amount of information that is coming about and the pace of discovery. It is really difficult to keep up.
This year I attended the European Congress of Obesity and also the American Diabetes Association, which was in my hometown, New Orleans, this year. It is really amazing the amount of information that is coming out in these meetings. It is truly astounding.
The amazing thing about it is that I am getting questions from patients about these medications. It is a very popular topic, not just with scientists and physicians, but also with patients.
Do you see the same thing in Korea, Soo? Are your patients interested in these medications that are coming out?
Dr. Lim: Yes. Before deep diving into that issue. Previously, many Asian ethnic group developed diabetes like the insulin-dependent type, but now more than two thirds of my patients are based on insulin resistance. We are now following where our trend is almost like the Western population. They are very interested in new agents like semaglutide or tirzepatide.
The problem is that sometimes even people who are not indicated for those medications come to my office practice and ask for them. That is really fascinating drug, but we are now very careful to choosing the right patient.
Dr. Ryan: Yes, same thing in the US. There is a lot of interest on TikTok and social media that is not really appropriate sometimes.
Look, I really want to focus our conversation today around what has been going on in these new developments in obesity. I am going to ask you both a question. That question is, what do you think have been the most practice-changing developments in obesity management that have occurred in the last 12 months? I am going to start with you, Stefano, and then we will move over to Soo Lim.
Dr. Del Prato: Yes, Donna, I alluded to it in my prior statement. The major breakthrough or the major thing that really interested me is the fact that we are recognizing more and more obesity as a disease, as a condition that is a disease per se. In the past, obesity was mainly considered the result of misbehaving of people and not following the diet, no physical activity, and so on and so forth.
We are realizing that obesity is indeed a disease. The Lancet Commission really was instrumental to try to bring that up. You may agree with some of the statements that are in The Lancet Commission. You may agree with them. What everyone agrees that obesity is a condition per se, and it is because of that it requires formal diagnosis processes and formal treatment.
By the way, it is not just a medical issue. It is a medical issue, of course. For instance, in my country, in Italy, we have now a formal law that define obesity as a disease. Because of that, there are initial recognition and reimbursement for the treatment of obesity.
Dr. Ryan: I did not know that. Amazing. What do you think is the most practice-changing development in Korea, Soo Lim?
Dr. Lim: Yes. Now it is changing from weight reduction itself to the weight maintenance period. When you take a look at the ATTAIN-MAINTAINstudy, which was very important because it addressed what happens after successful weight loss. In that study, as you know, the patient who had previously received tirzepatide or semaglutide in SURMOUNT-5 was switched to oral orforglipron or placebo.
Orforglipron helped maintain a much larger proportion of prior weight reduction than placebo, about maybe 75% after tirzepatide and 79% after semaglutide.
The message is very clear to me: obesity requires long-term management, and oral therapy may become an important maintenance strategy because it can help us maintain our patient well because it is oral therapy and it must be way cheaper than injectable therapy. It does not need to cold chain, etc.. Now we are entering into oral medication.
Dr. Ryan: I am so glad you said that. It is a major problem in the United States. We have really good uptake of these medicines, but we really have a problem keeping people on them. About two thirds of the people who are prescribed semaglutide or tirzepatide in the United States have stopped it by 12 months. That is not good. These are chronic disease medications that need to be taken over the long-term.
I agree. The emergence of these oral medications and studies like ATTAIN-MAINTAIN that show how to transition from an injectable to an oral are going to help with that. It is so interesting to talk to my two colleagues from around the world because there are some real differences in the patient populations that we treat.
In the United States, we have really a major problem with severe obesity in terms of very high BMI. I do not think that exists in Korea, Soo Lim. It is a different population. Tell us a little bit about the obesity phenotype in Korea and how that that impacts your treatment?
Dr. Lim: Yes. That is very relevant to today's topic. In Asian patients, I mean the East Asian and South Asian both, I am particularly interested in therapies that reduce visceral fat and ectopic fat. Because for example, type 2 diabetes, the fatty liver, now known as the metabolic dysfunction steatotic liver disease, or other cardiovascular event often occurs at lower BMI compared to Western counterpart.
Therefore, the real clinical question is not only weight reduction, but whether we can reduce the visceral fat or liver fat or the intramuscular fat and improve insulin resistance and protect beta cell function. We may seem to be relatively not severely obese, but when we see our patient, they tend to have larger, greater visceral fat in their abdomen. Or as you may know, the prevalence of fatty liver previous term is quite prevalent, almost same as the Western population over 30%. So we have to focus on that part.
We strongly recommend to measure waist circumference in our clinic or sometimes body composition analysis when available. We try to find the excess fat itself, not just BMI.
Dr. Ryan: I think that focus on obesity being excess abnormal body fat, that concept is really worldwide. Stefano brought that up with The Lancet Commission and their focus on the true diagnosis of obesity, which is excess abnormal body fat, which is impairing health.
Stefano, are there issues that are regional in Europe? Is all Europe alike or are there differences in countries in what is going on with obesity management?
Dr. Del Prato: Yes. As you know, Europe is made by different countries with different regulations. Actually sometimes even within the same country, you have different regulation and different administrative processes for the treatment to be approved and actually reimbursed.
I have to say that by and large, I do not think there is any European country that currently is reimbursing treatment for obesity. While some of the drugs that we have been using for type 2 diabetes are also commonly used also for the treatment of obesity, the high dose semaglutide, for instance, or tirzepatide are currently reimbursed for type 2 diabetes, they are not for obesity.
Things may be changing. From a country to country, there are different processes going on. This is something that we need to look into the near future. What I think and I want to go back to what you started off with, Donna. We have been learning more about the obesity. We have been learning more about what is really the meaning of an excess adipose tissue and even more to have an excess of a sick adipose tissue, because that is important to make a distinction.
One thinks the total amount of adipose tissue and one thing is specific area of the adipose tissue, and to which extent the adipose tissue is working in a wrong manner and driving inflammation, for instance, and so on and so forth. What we probably be learning in the future, it will really have a better understanding not only of the obesity as a disease, but also as obesity as a heterogeneous condition, and to have a way to drive and to specifically more indicate treatment for different subgroups of people with obesity.
That is the process that I can see going on in Europe. The Lancet Commission alluded to that starting speaking about pre-obesity and then obesity and then clinical obesity and so on and so forth. We are just at the beginning. We are just at the dawn of it. Right?
It is reminiscent to me to what we have been discussing over years and years for type 2 diabetes. Initially it was just hyperglycemia and then realized that there is a lot of heterogeneity, and that heterogeneity needs to be factored in, in order to provide the best treatment to the best or the right or the most right person.
Dr. Ryan: One thing that I see happening when I attend our professional meetings is that there is always seems to be a symposium about body composition and the effects of weight loss on body composition, on fat mass and on lean mass. This seems to be something that is in the forefront of everyone's mind. It all relates to the heterogeneity of obesity and how different our patients are and how it is really one size does not really define everyone with obesity.
Dr. Del Prato: Yes, exactly.
Dr. Ryan: I want to ask you guys what do you think about emerging studies? What do you think is the most exciting emerging evidence that is coming out, that has already come out in 2026 or that you are anticipating to come out later this year? What do you think, Stefano? You lead off.
Dr. Del Prato: Yes. This has been an incredible learning curve over the years. We started off with, as you may remember, with liraglutide, and now we are looking for drugs that are becoming more and more effective to the point that we are considering pharmaceutical bariatric surgery. Because the kind of body weight reduction that we are seeing really is approaching what can be achieved with bariatric surgery.
I really like to distinguish what I see of interest in the near future is the injectable and the non-injectable. For the injectable, we have this incredible data, very impressive data for retatrutide. We are moving from a single activator of a GLP-1 receptor to a dual, including a GIP and now the glucagon and the triple agonism on these three receptors is associated with an unprecedented body weight reduction.
That will be some of the line. Of course, the drugs that we are going to use may have different indication within the obesity area. Soo already mentioned, for instance, about MASLD and MAFLD, and some of these new drugs are more generated for and more specifically directed to the liver rather than the obesity by itself.
Also the other thing that has been already mentioned is the oral GLP-1 activators. I am wondering when we are going to see the oral dual activators. Because if I see the way things are going, I would not be surprised to see anything like that.
Also what is important is to consider the multiple point of attack on the pathophysiology of obesity. It is glucagon. It is GLP-1, this is GIP, but it can be also amylin or amylin receptor activation. We have the recent data from the CagriSema for instance, also very interesting.
It is really becoming a very fascinating world. It remains also to define or to identify the best strategy to keep the people on treatment. I totally agree with you, Donna. Sometimes I am asked from people, “When I get to the right body weight, should I stop?” I ask, “If I give you an antihypertensive treatment and your blood pressure go down to normal levels, are you going to stop the treatment? You are not, is not it?” Because that is something that you need to treat. That is one thing.
The other thing that we need to tackle is that excessive body weight reduction can be associated with a waist reduction in the lean body mass. There will be some pharmacological solution in the future combining this potent body weight-lowering drugs together with muscle preservation molecules inhibiting, for instance, myostatin and so on and so forth.
Also, we, as physicians, need also to have a comprehensive approach and remind our people that maybe right now, the best way to preserve the lean body mass is to stand up and work out, because that is also important to keep in mind as well.
Dr. Ryan: Yes. Excellent. You are talking about retatrutide, and that was amazing that the presentation at the American Diabetes Association showed that you could have up to 28% weight loss on average with the top dose. That is a lot of weight loss.
Soo, do people in Korea need that amount of weight loss?
Dr. Lim: I do not think so. Instead, we are more focusing on body composition. 15% to 20% weight reduction would be good. More than that, I do not know. Most of preservation is very important, as Dr. Del Prato already mentioned. Compared to Western people, many Asians relatively tend to have less muscle mass. Muscle loss with injectable therapy is very critical to those patients, especially elderly population with obesity.
We are now strongly recommended to take high protein diet and the resistance exercise at the very beginning, because the rebound phenomenon easily develops after stopping the GLP-1-based therapy.
Continuing Del Prato’s comment, I am very much interested in the survodutide. In a recent paper titled SYNCHRONIZE-MASLD, survodutide, which target GLP-1 and glucagon receptor co-agonists reduced MRI measured fat fraction in the liver. More than 80% of survodutide treatment group achieved 30% reduction in liver fat compared to placebo.
We are more now interested in the organ protective effect of this medication, not just for BMI or the weight reduction itself. The liver fat and pericardial fat or intramuscular fat and sometimes peripancreatic fat or perirenal fat is more relevant to our population.
Dr. Ryan: Yes. Excellent. That is true. We have got one vote for retatrutide as being the most exciting discovery of 2026. Another vote for survodutide. You are making it hard for me. There is so many things that are happening, but I am going to cast my vote for the most exciting thing to happen is the emergence of our first long-acting amylin analog, cagrilintide.
It is being co-administered along with semaglutide. We are expecting that to be approved in the United States either later this year or early next year. Coming behind those two molecules, we are seeing a number of agents that are going to try to capitalize on amylin, along with GLP-1 receptor agonism.
That appeals to me for a number of reasons. One reason is that targeting the amylin and calcitonin receptor could have a benefit on body composition. It could have a benefit on bone. There is even some evidence that it could have a benefit on muscle. We are going to be watching those body composition studies that come out with our amylin analogs very carefully.
The other thing that is really appealing about that molecule to me is the fact that it is insulin sensitizing. Our GLP-1 receptor agonists, they are incretins. They have an effect by promoting insulin secretion in the presence of a high blood glucose. Amylin is an insulin sensitizer and I really like that, especially in early diabetes and in prediabetes.
I am looking forward to seeing more data coming out about cagrilintide and semaglutide together called CagriSema, or on some of the new molecules that are going to follow this. There is one, zenagamtide, that is in the works. Another one, eloralintide. I will be looking for evidence about both of those. Lots of exciting things happening here.
Let me see if my colleagues have any other comments that they would like to make about what is going on in the developments that we see promoted at our professional meetings. Stefano, anything?
Dr. Del Prato: As I mentioned before, this is a very exciting time. You also now announce newer and more and more drugs. What probably needed to be in the future is how are you going to select these drugs? I am a strong believer in individualization of the treatment. We may also wonder to which extent one drug may be fitting some people and another drug may fitting the need of other individuals, so that will require extensive studies and extensive evaluation.
There is a potential there for having multiple ways to attack different mechanisms underlying obesity to provide a more personalized treatment. That is something that really intrigues me to some extent as it intrigues me also related to the treatment of type 2 diabetes and the two things are very much similar to some extent.
The other thing is a matter of concern, if you allow me, because the number of people with obesity is becoming so outstanding. It is becoming really incredibly high. We also should consider what can be done in order to keep the medicalization of the society for those requiring that.
You mentioned before, Donna, that we have a lot of people with a poor adherence. After first year, 50% of the people often are off, multiple reasons, including the course sometimes, because that is also a limitation in some area of the world. Also that is what we need to do is really to try to gain the best out of what we have in order to be able to really targeting those requiring the treatment and to keep those people under the treatment.
In the meantime, to set up preventative measures to reduce the slope of the rise of the epidemiology of the prevalence of obesity worldwide. We need to be more comprehensive, not just remaining focus, which is important definitely on the people with obesity, but also we should work on preventing obesity as much as possible.
Dr. Ryan: Yes, we really need some models for prevention. We really do not have any that we know that work. We need some models for prevention.
Dr. Del Prato: Yes, I agree.
Dr. Lim: Yes, I agree. Yes.
Dr. Ryan: Everyone is in agreement on that. One of the amazing things that has emerged over the last few years is the fact that our medications not only have effects on weight loss, and they not only improve health mediated through weight loss benefits, but they have effects beyond weight loss. We know the cardio-protective effects of these drugs. The GLP-1 receptor agonists also are known to slow the progression of chronic kidney disease. We have effects on obstructive sleep apnea.
These disease modifying attributes are very important. I was so fortunate to be part of the SELECT trial that showed the cardiovascular event reduction with semaglutide. I am really looking forward to the SURMOUNT-MMO study reading out in 2027. We all hope this is a class effect, but we really need to demonstrate that with this study. What do you guys think?
Dr. Lim: Yes. In the SELECT trial, we found that 20% reduction in 3-point MACE development with semaglutide 2.4 milligrams. I strongly agree. I cannot agree more with Donna because the SURMOUNT-MMO trial should show a favorable result because it is for our patient.
Obesity is a chronic disease, so when we reduce body weight and especially visceral fat, it should lead to a beneficial result in not only cardiovascular but also renal or hepatic outcomes.
Dr. Ryan: Very good. Stefano?
Dr. Del Prato: Donna. Yes, of course, it is very exciting once again, but these are really something that we know and which would be very important and very interesting. We know that, for instance, using semaglutide in the SELECT trial or using tirzepatide in the SURMOUNT-1 trial, it was shown that both semaglutide and tirzepatide can prevent progression towards diabetes in an incredible manner.
73% relative risk reduction for semaglutide in the SELECT. 93% in the SURMOUNT-1. Actually, what is even interesting is that not only you do prevent the progression toward overt diabetes, but actually have the vast majority with tirzepatide, all the people with more than 10% of body weight reduction, 98% of them return back to normal glycemia.
Actually, this is very interesting because we have now data showing that reverting back to normal glycemia. This is a post-hoc analysis of the DPPO trial, the follow-up of the Diabetes Prevention Program as well as in the Da Qing trial that is also prevention study that was done in China, that those people that were able to remit or to revert to normal glycemia after the first year, they had a significant reduction in all the cardiovascular outcomes 20-plus years later.
We not only have the potential for those people with a high cardiovascular risk or high kidney risk to provide them with a preservation effect or protecting effect of these drugs. Also, we can start acting earlier and really to prevent the development of condition that is really going to impact into the quality of life of people living with obesity.
Dr. Ryan: I could not agree more. One thing that has happened in the United States is that we are finally having our government health insurance. Medicare has agreed to pay for these GLP-1 medications for pre-diabetes. This is new.
I am sorry, Soo. I cut you off.
Dr. Lim: No. Now we have to think about the whole treatment journey in obesity management. The first phase is induction of weight loss, and the second phase is maintenance. The third phase is complication focused care, as I mentioned. For example, a patient with obesity and type 2 diabetes may benefit from a therapy with strong glycemic and weight reduction.
A patient with obesity and at-risk of mortality may need a therapy with strong effect on liver fat and inflammation. The third case is a patient with sarcopenic obesity may need careful nutritional support or resistance exercise while receiving pharmacotherapy such as amylin analog or Donna already mentioned. The future obesity care will be more phenotype based that I am insisting.
Dr. Ryan: I am looking forward to that. Right now we tend to have a one-size-fits-all approach and it is not right. We need to improve our guidance. It takes so long for evidence to make its way into our guidelines. I am really happy to be talking to you guys today, because what we are seeing is we are seeing evidence emerge that is going to affect our guidelines. We really have some astounding things that are happening very rapidly in the field. It is a great pleasure talking to you about this.
I have run out of questions. What are the questions can I ask you?
Dr. Lim: The final message?
Dr. Ryan: Okay. Yes. Give me a final message, Soo Lim?
Dr. Lim: My take home message is that obesity management is now entering a new phase, so we should move from BMI-based short-term treatment to complicated-based long-term maintenance care. The future will be about using the right therapy for the right people at the right time.
Dr. Ryan: Okay. Stefano?
Dr. Del Prato: I cannot have much to add to what Professor Lim has said. Just only one final consideration. We do have now weapons to fight diabetes. Please stay tuned. More are to come.
Dr. Ryan: That is right. Absolutely. Let us see what I will make for mine. We are so fortunate to be at an age where we have choices, choices to help our patients. We have injectables. We have orals. We have small molecules. We have peptides. We have medications that produce robust weight loss, really rivalling bariatric surgery. We have medications that have special properties that can be targeted to special diseases, for example, MASH, liver disease, for example, cardiovascular diseases.
We have medications that have indications for obstructive sleep apnea. Identifying the right medication for the right patient is where we are really going to be putting our efforts going forward. It is such an exciting time. I am really grateful to my colleagues for sitting down with me and discussing this. Thank you both very much.
Dr. Lim: Thank you.
Dr. Del Prato: Thank you.
Jill Frost: Fantastic. Y'all did a great job. I think y'all could just keep talking forever and ever on this topic.
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