[00:00:00] first, let's go over the European Congress of Obesity twenty twenty-six, From Weight Loss to Long-Term Management. I'm gonna turn this over to my colleague, Dr. Sue Lim. Thank you, Donna. Now I will cover the key obesity data from ECO or ECO twenty twenty-six. The main theme from E-ECO this year is very clear. Obesity care is moving from simple weight loss to long-term management. We now need to think about several important, uh, issues as shown here, how to achieve enough weight loss, how to maintain that weight loss, how to preserve muscle and physical function, and how to tailor or how to match treatment to each patient's needs.

This is especially important in real-world practice because obesity is a chronic disease. First, OEC, [00:01:00] OEC is four, which showed that oral semaglutide twenty-five milligram can provide meaningful weight loss and may become another oral GLP-one option.

Second, step one-- uh, step up, sorry. Step Up showed that a higher dose of semaglutide, seven point two milligrams, may help patients who need greater or faster weight loss. Third, Redefine 1 show that cagrisema, the combination of cagrilintide and semaglutide, produce large weight reduction and also raise important discussion about body composition, not just, uh, weight itself.

Fourth, Obtain Maintain addressed a very practical question. After successful weight loss with injectable therapy, can we maintain the benefit with an oral option? Taken together, these show that obesity treatment is becoming [00:02:00] more individualized with different options for induction, transition, and maintenance.

 OBTAIN-MAINTAIN showed that long-term weight loss can be maintained after switching to oral incretin-based therapy. This is one of the most practical studies for clinicians. OBTAIN-MAINTAIN asked what happens after patients have already lost weight with injectable tirzepatide with semaglutide in some month five.

P- participant were then switched to oral orpolipron or placebo. The key result is that oral orpolipron helped preserved much more about the previous weight loss with, uh, a previous weight loss than placebo. In tirzepatide cohort, a patient maintained about seventy-five, seventy-five percent of prior weight loss with orpolipron.

In the [00:03:00] semaglutide group, patients maintained about seventy-nine percent with orpolipron, which was significantly greater than placebo. So clinically, this supports the concept that obesity treatment should not stop after successful weight loss. We need a maintenance strategy. Now, moving, uh, from maintenance to treatment intensification.

Mm, let's look at the step-up post hoc analysis And next is the step of a post hoc analysis. Before discussing this post hoc analysis, uh, let me briefly summarize the original Step Up trial. Step Up, Step Up was a phase three B trial in adults with obesity without diabetes. It compared once-weekly semaglutide seven-point-two milligrams with semaglutide two-point-four milligrams and placebo over seventy-two weeks.[00:04:00]

Semaglutide two point... Uh, sorry, semaglutide seven-point-two milligram produced greater weight loss than semaglutide low dose, here two-point-four milligrams, and placebo. Eighteen point seven percent versus fifteen point six percent and three point nine percent respectively. The Step Up post hoc analysis give us, give us another important message.

In this analysis, early responders were defined as patients who achieved at least fifteen percent weight loss by week twenty-four. With semaglutide seven-point-two milligrams, early responders achieved twenty-seven point seven percent weight loss at week seventy-two. Even among the other responders, weight loss was still substantial.

And this data tells us, tell us two practical things. First, higher [00:05:00] dose semaglutide may be useful for patients who need greater weight loss reduction. So nowadays, you know, semaglutide two-point-four milligrams widely used across the globe. But in this study, they used semaglutide seven-point-two milligrams.

Second, early response monitoring may help guide treatment decisions. So the Step Up post hoc analysis data support a more active and individualized approach to obesity treatment. Beyond higher dose of GLP-1 therapy, another important direction is combination th- uh, therapy.

Redefine 1 is important because it moves the discussion beyond the total body weight. CagriSema combines semaglutide, a GLP-1 receptor agonist, with cagrilintide, an amylin analog. In REDEFINE 1, this combination produced about 20% weight loss at week 68, which was [00:06:00] greater than placebo.

But the key point here is body composition. About two-third, two-thirds of, of the weight reduction was from fat mass, and about one-thirds, one-third was from lean soft tissue mass. This is, uh, clinically very important. When we use power plant obesity medication, we should also think about muscle mass, muscle strength, frailty risk, and physical function, especially in older adult or a patient with sarcopenic obesity.

Next, I want to highlight the maintenance therapy again. In OBTAIN-MAINTAIN and SUMMIT-MAINTAIN studies, maintenance become an actionable treatment phase. Traditionally, we usually focus-- we mainly focused on weight loss induction, but now maintenance should be considered a separate, uh, and active phase of obesity [00:07:00] care.

The treatment phase, uh, pathway can be divided into three steps, as is shown here down there, the induction, transition, and maintenance. During induction, we usually try to maximize, uh, benefit while main- maintaining and managing tolerability. During transition, in the, in, in the middle, if we switch or step down therapy, we should do this only with a clear maintenance strategy.

During the maintenance, uh, period, the goal is to preserve weight loss, physical function and dietary quality and cardiometabolic benefits. OBTAIN-MAINTAIN is very important because it suggests that oral therapy may help maintain weight loss after injectable therapy. This may be especially useful for patients with injectable burden, injection burden, travel issues, some, uh, cold chain problems in some countries, uh, cost concerns in [00:08:00] many countries or access barriers.

Thank you very much, Su Lin. I want to talk about what happened at the American Diabetes Association this year in June 2026 what I think happened at ADA is we saw even more of these messages about new things are coming.

Probably the highlight of the ADA meeting was the presentation of the retatrutide data. So retatrutide is a triple agonist. It's targeting GLP-1, GIP, and glucagon. This data has been eagerly anticipated because we believe that by combining three targets in one molecule we can get additional weight loss, and perhaps even additional disease-modifying attributes.

So one of the most, uh, interesting and well-attended and exciting events at ADA was the presentation of Triumph 1. This is the phase three study of retatrutide in three doses, 4, [00:09:00] 9, and 12 milligrams. And so I'll be talking to you a little bit ab- about that, uh, and especially, uh, about h- the glycemic and, uh, cardiometabolic benefits associated with retatrutide.

Another, uh, very interesting presentation was with servodutide. Now Servodutide is a dual agonist, a single molecule dual agonist, and it targets both GLP-1 and glucagon. It's thought to have a special affinity for removing liver fat because of the glucagon receptors in the liver.

Um, so we think it's going to be a, uh, a good m- agent to be using for patients who have fatty liver disease or steatotic hepatitis. So Synchronize One Um, w- results were, uh, released at ADA this year, and, um, it, they, it looked at two doses of ser- servo-dutide, 3.6 [00:10:00] milligrams and 6 milligrams. So in the phase three studies, uh, for Cagrisema, REDEFINE are, are the studies that occur in individuals with o- overweight and obesity but without type 2 diabetes, and REIMAGINE are the studies in type 2 diabetes. So there was a lot of interest in this combination and their effects on glycemia because, you know, the targeting, that long-acting amylin analog targets both, uh, amylin, uh, and calcitonin.

And we believe that amylin, um, receptor agonism is, is, uh, produces ins- increased insulin sensitivity. So it's not just an incretin effect. It promotes insulin sensitivity, so we're very interested in the results of REIMAGINE 1, 2, and 3 with Cagrisema. Uh, there was also, uh, a presentation of another oral molecule that's in the pipeline, [00:11:00] Elacoglipron, 75 milligrams.

So the SOLSTICE and VISTA studies discussed oral Elacoglipron. We're going to have more oral options coming down the road. And then finally, uh, a very interesting debut of Bareobenetide. Bareobenetide is a GLP-1 receptor agonist, and this one was developed to be long-acting. Um, so the idea is that if you have a, a molecule that is long-acting, it will have a slower uptake and a longer duration of action.

The pharmacokinetics are a little different of this, of this molecule, of this GLP-1 So let's drill down a little bit on that Triumph 1. This was the phase three study of, uh, retatrutide, uh, in individuals with overweight and obesity without type 2 diabetes. And this produced [00:12:00] really the best average weight loss we've seen to date with any obesity medication. So there are two ways we analyze the data.

One is with an efficacy es- estimate, and those results on average are a bit higher, and the other is with a treatment regimen, uh, estimate, and that is more like an intention to treat analysis. And those results are still excellent, but they're just a bit lower in terms of mean weight loss. But at the top dose of retatrutide, the mean weight loss by the efficacy estimate was 28.3%.

This is the greatest mean weight loss we've seen to date. The 9 milligram dose produced on average 25.9%, and the 4 milligram dose 19%. Really excellent weight losses, all compared to placebo weight loss of 2.2%. Now, uh, these results are, are, are at 80 weeks. There is, of course, a dose escalation that's required, and then this is after 52 weeks on that top dose.

So I'll just, uh, review [00:13:00] the treatment regimen estimates. They're also excellent, but just a bit lower. So 25% for the 12 milligram dose, 23.7% for the 9 milligram dose, and 17.6% for the 4 milligram dose. Now, the retatrutide, uh, data continued, uh, with Triumph 1, and, uh, what this, the study, uh, after, after 80 weeks, for the first 500 people who had, uh, achieved, uh, their, um, their assigned dose, they were allowed to enter into an extension period, uh, where they could, uh, go to their maximal tolerated dose.

And so that continued out for 104 weeks, so two years of retatrutide, uh, exposure. And so, uh, those data also were excellent, and it showed up to 30% average weight loss out at two years. This is [00:14:00] truly, um, uh, a remarkable amount of average, uh, weight loss that we're seeing here. Now, this drug is still investigational.

It will have to go through the regulatory authorities, and I'm sure they will be scrutinizing this for the, to make sure that we are not getting too much weight loss and too rapid weight loss, which believe me, can occur. So we're gonna be watching this, uh, retatrutide with a lot of interest. I think it offers promise for our patients who have not responded well to, uh, just a GLP-1 agent alone or to a GLP-1 GIP agent.

So adding this third target may increase weight loss, and we may be able to salvage some patients who are not responding very well to one of our other medications. I think it also holds promise for people with larger BMIs because, uh, they need more weight loss to achieve some of our, uh, health, uh, oriented anthropometric targets.

Now, two [00:15:00] medications are on my list to discuss with you from ADA, and one of those is elacoglipron, 75 milligrams. Uh, it was, it had data presented, showed that it produced moderate weight loss and also had improvements in A1C. Uh, another, um, uh, m- medication that was presented was injectable bariatide.

And bariatide is a long-acting GLP-1 receptor agonist. Um, and so it, it, they did pr- present some data, uh, from phase two where they extended the dosing to one month, so one-month injections instead of our usual weekly injections. That was very interesting. So both of these agents are still investigational.

We're looking forward to more data on them to see, uh, how they m- might help our patients. But, uh, I think what it all, uh, signals is that we're going to have to look at our patients in a slightly different way. [00:16:00] Now that we have more tools in our toolbox, we're gonna need to better personalize our approach to individual patients

so my overall perspectives from the, American Diabetes Association meeting this year is that we're going to have increased treatment options. So overall, more treatment choices, greater need to individualize our therapy.

So the message to clinicians is, yes, we need to assess our patients not just with BMI, but we need to be looking at where body fat is located, we need to be looking at complications of obesity, identifying cardiometabolic risk, because all those things can drive our treatment choices. We need to match. We need to match our patient profiles to the profiles of the individual medications that are emerging, because we're gonna have a lot more options than we have now.

And then as Sue Lim so eloquently stated, [00:17:00] obesity treatment requires that we think about maintenance when we begin the weight loss journey. So, uh, we, we will, we always have to have that concept in mind for when we manage patients with this chronic disease,

 what findings do you think are, are most likely to influence how we talk to our patients, Sue Lim? \ I would say the most practice-changing message from ECO 2026 is the treatment framework, changes in treat- treatment framework.

The ECO data reinforce that obesity care should include induction, transition, and maintenance. Previously, uh, most doctors just focused on induction. M- now we have to, uh, we have to shed a light on the transition and maintenance. So, a patient... for patient conversations now, I would write highlight the three point, um.

Uh, the first, attain maintain support, the idea after successful [00:18:00] injectable therapy, we need a maintenance strategy, not treatment discontinuation. Second, in the step-up study, we found that the, some patient may need a higher dose or a stronger anti-obesity medication. And the third one is now we have many promising, uh, the agent in the near future. Absolutely. So in the United States, we have two oral medications, two GLP-1, uh, receptor-targeted medications. Do you have oral medications available in Korea?

Uh, yes, but not this type. The, we h- do have the, the two, uh, the oral medication for obesity medi- chronic obesity medica- medications.

So such as, uh, the pantoprazole pyramid combination. But no GLP-1s ... an- another oral GLP-1 at all. Mm-hmm. Uh, well, um, I think it's coming. [00:19:00] This is going to come around the world. So I think your point about attain, maintain, and, and surmount, maintain, I think those are, they're very clinically relevant because patients tell us that they don't want to take the injections forever.

So I think the opportunity to transition to an oral medication is highly clinically relevant in the United States right now, but coming soon to Korea, right? Yes, I'm, I'm very, very looking forward to, uh, that those drugs will be available soon in my country or in many other regions. So some of the things we talked about are really on the watch list.

So certainly servodutide is not approved yet in the United States. We'll be watching that, uh, carefully. And the same thing goes for retatrutide. That is another, uh, agent that has not been looked at by our regulatory authorities, and that's another one, uh, that's on the watch list. We're [00:20:00] interested in both of those because, again, the opportunity for personalization.

Okay, let's move on to, uh, how we actually, uh, individualize our obesity management, uh, medication selections. So I think we're always thinking about efficacy, oral ver- versus injectable, tolerability profiles, whether the patient can afford it, access it or not, uh, how the patients will adhere to it, are there any side effects that we need to avoid, and is there, are there any risk profiles that we need to avoid, and then finally, and most importantly probably, patient preference.

Because if the patients don't take these medications, they can't benefit them. Right. So yeah. So, S- Soo Lim, what is your overall sort of, um, uh, what is your overall impression of what is occurring in our scientific meetings that may actually benefit, [00:21:00] uh, our patients in the long run?

Uh, so as, uh, you-- we already discussed, now we have oral options as a maintenance therapy, and the, uh, the stronger options with, uh, other incretin-based or neutral, uh, nutrition stimulated hormone-based therapy.

But, uh, would like, I would like to highlight the, uh, muscle, uh, mass loss. So for older adults or patient with, uh, chronic obesity, which is more often in, uh, our region, in my region, I will pay close attention to body composition, uh, or muscle strength, protein intake, and physical function. So the... I, uh, I was very much interested in the result from REDEFINE 1, uh, which is very relevant to our region because it produce larger weight loss, but, relatively, uh, lower muscle loss and, uh, rel- the greater the fat loss. So, [00:22:00] uh, in, from Asian doctor's perspective, Asian patient's perspective, we don't need the super strong medication such as 30% reduction in most patients with obesity, but we need more, you know, f- uh, agent more focusing on good body composition.

So, uh, less muscle mass loss and high, greater fat mass loss. Yeah. You know, Su-Lin, we talk about the Asian phenotype, uh, being one where there's low lean mass, and there's a, this propensity to store excess body fat centrally, visceral adiposity, ectopic body fat- You're right ... uh, deposition. But, you know, we see this phenotype in some individuals in the United States who are not Asians.

So I think there's a lesson there for everyone, and that lesson is that obesity is not really just about body size, which is what BMI is measuring. It's about where body fat is located and how [00:23:00] it's impacting your health one thing that's happening in the United States that's important, I think, is that we're beginning to see some inroads in paying for obesity treatments through Medicare.

And so we started July 1st on this program called Medicare Bridge, which allows patients who have the government insurance, uh, that is, that is called Medicare, to get the GLP-1 receptor agonist under certain conditions, certain requirements, for $50 out-of-pocket copay. Wow. So what this... Yeah. What this is doing is is we're finally, we're finally seeing, uh, some, uh, that obesity is going to be covered, um, by some of our insurers.

So that is a very good thing. What is the situation like in Korea and in Asia- Uh ... in terms of reimbursement?

Uh, this, it is a kind of shame, but unfortunately, uh, the anti-obesity medication is not, uh, covered by, uh, governmental [00:24:00] insurance. Some... And the private, uh, insurance may cover, uh, those medications, but, uh, the, uh, the anti-obesity medication such as injectable type of, uh, medications such as tirzepatide or semaglutide is quite expensive, even though it is little bit cheaper than in the States or in, in other, uh, European countries, but still expensive.

 So I think overall what we're seeing, uh, happening at these meetings is that there is more emphasis on access. And so we're, we heard presentations at ADA that real- that discussed trying to design treatments that could be more affordable by making them longer acting, by making them more easy to manufacture.

And so the opportunity f- with these small molecules is that they don't require the cold chain, they don't require an injection. They may... That, that they can be sta- shaped, self, shelf [00:25:00] stable, and that they may- Right ... uh, you know, that, so that all of those things would pro- promote access. So I see that as a, a very positive thing that's coming out of these meetings.

think we need to consider the differences, the regional differences in obesity, uh, across the world. You know, we're used to thinking about this high income, high access country in the United States, but we need to consider, uh, that obesity is a global problem. There will be one billion people with obesity in the world, uh, by 2030, and we need to have solutions that work in resource-constrained settings, so with affordability, which don't require a cold change, which may...

That means there may, we may need more oral options and so forth. And we need to recognize the cultural diversity that occurs across the world, and not all patients are the same, and [00:26:00] we need to, we need to, uh, we need to, to identify, uh, profiles of patients across the world who may benefit from dip- slightly different approaches.

And finally, I think there's a need for, uh, recognizing that some regions have a high rate of fatty liver disease, of MASH, and we need to take that in, into account. Su Lim, do you have any comments? Uh, yes. In, in regions with high burden of type 2 diabetes and, uh, fatty liver or steatohepatitis liver disease, uh, especially in Asia, we should not, uh, rely only on BMI.

We... Many patients develop metabolic, uh, impairment at lower BMI, uh, so healthcare providers should prioritize cardiometabolic screening, uh, waist circumference, gly- glycemic status, body composition. So, uh, the notice, uh, American Heart Association recommend the CKM concept, cardiovascular, kidney, and metabolic [00:27:00] concept for, uh, chronic disease management.

So we can apply those, uh, concept to, uh, our patient with, uh, obesity. So we now more focus on the, uh, their met- cardiometabolic risk assessment, not just on BMI alone

so let's finish up with some key takeaways for your practice. Look, the meetings at the European Congress on Obesity and the American Diabetes Association really reinforce a new framework for how we conceptualize obesity.

It is not just about body size. It is excess abnormal body fat that is impairing health. We need to be assessing risk and matching our obesity management medication to the patient profiles, and we always need to plan for maintenance at the very beginning of our treatment plan. So I think what matters most for primary care physicians is that obesity treatment must be guided by the [00:28:00] patient complications, by cardiometabolic risk, by our patients' functioning, their goals, their tolerability, their ability to access medications, their ability to adhere to medications, and long-term sustainability.

This is more than BMI. BMI can be a screener, but it is not the end-all and be-all. And finally, let's pay attention to emerging data. These are like signposts of what's going to be coming down the road next. So I think it's changes in our treatment pathway only occur after approval of medications. But for now, we can get an idea of what's coming along.

So let's wait to change our treatment patterns and pathways, but let's be aware of what's happening coming soon. But I wanna finish up, um, with having you tell us what you think, uh, is a key takeaway. What is one practical change that primary care [00:29:00] healthcare providers, uh, can make now to improve their obesity treatment?

What's your recommendation? Uh, Jane. One thing. Okay. I see. So my final mes- uh, message is very simple. So ECO and ADA 20- 26 data reinforce that obesity care should not be BMI based or short-term. It should be risk based, complication based, and long-term. So for primary care physicians, the practical approach is to assess risk, tailor treatment plan to each patient, and plan maintenance from day one Oh, how could I improve on that?

I'm going to second Sue Lim's key takeaway, and that is obesity is a chronic disease. Let's treat it seriously. Let's treat it earlier. Let's not wait until our patients get all of the complications. Let's intervene earlier. Sue Lim, I wanna thank you so much. I enjoyed doing this with you. [00:30:00] The pleasure is mine