Episode 71: 2025 Algorithm for the Evaluation and Treatment of Adults with Obesity/Adiposity-Based Chronic Disease Overview

[MUSIC] Welcome to ACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aac.com/podcasts. And now let's meet the endocrine expert who will be talking with us today. Hello and welcome to our ACE Podcast focused on ACE guidance documents. I'm Dr. David Lee, Professor of Medicine in the Division of Endocrinology at Eastern Virginia Medical School at Old Dominion University in Norfolk, Virginia, where I also serve as our Endocrinology Fellowship Program Director. Today we're discussing the 2025 ACE algorithm for the evaluation and treatment of adults with obesity/adiposity-based chronic disease. The latest update to ACE is clinical guidance on obesity management. Joining me are Dr. Carl Nydalski, Chair for the Algorithm Writing Group, and Dr. Tipton Degarvi, the Committee Vice Chair. Thank you both for being here today. Thank you. My pleasure. Dr. Nydalski, can you start by introducing yourself, including your background in obesity medicine and endocrinology? Yes, sure thing. So I did my training in the Navy, active duty for internal medicine residency, and then endocrinology fellowship at Walter Reed National Military Medical Center. And actually between those two trainings is when I started to get into obesity medicine and was part of the first class of the American Board of Obesity Medicine. And when I was a fellow, I was actually introduced to some ACE obesity experts, including Dr. Garvi, and they took me under their wings and helped continue my training and also involvement in some of the early renditions of ACE obesity guidelines and algorithms. And that really helped stimulate a lot of my passion for doing a lot of this extra academic work. And then after getting out of the Navy, I've been in Michigan, an assistant professor of medicine at Michigan State University, and just recently went from corporate health care to starting my own practice here in Holland, Michigan. And Dr. Garvi? Yeah, thanks David. I'm a professor, I'm endocrinologist and professor at the University of Alabama at Birmingham. I've been an academic practice and researched my entire career. I was a happy diabetologist for most of my career studying mechanisms of human insulin resistance. And then did a clinical trial maybe 15 years ago now with Benjamin Topiramate and just saw people losing weight 20 pounds, 30 pounds. And I said, wow, we can really help a lot of patients with these kind of tools. And I became more passionately involved with obesity and obesity medicine models of obesity care and clinical trials with these medications. And I had the good fortune to work with ACE that really provided a platform for the 2016 guidelines for clinical management of obesity. And other position statements and etc. And this our most current algorithm as well. That brings me to the present David. Let's start with an overview. Carl, why was it important to update the 2016 ACE obesity algorithm? And what major changes in science or practice prompted this 2025 update? Well, mostly, I think our 2016 guideline and algorithm was very forward thinking. And like Dr. Garvey said, it was really the first guideline that I can remember and aware of that instead of just classifying obesity based upon body mass index, BMI or even other anthropometrics, it was changing the care model to stage the severity of disease in a complication-centric manner that that we'll talk about. And going beyond just the disease of obesity and ultimately with the concept of adiposity based chronic disease, really covering a bigger swath of the disease process. But since then, I mean, it's been almost 10 years. We've had great advancements in our medical therapy in addition to some surgical and procedural therapies. And it really was necessary to make this update because of our new advanced therapies. And I think more global attention talking about obesity and adiposity based chronic disease, not just from our niche share. And kind of following up on that, Tim, can you summarize some of the biggest differences in the 2025 version with what's new or significantly expanded compared to the 2016 algorithm? Yeah, I think, you know, the 2016 guidelines were really the first guidelines to explicitly recommend a complication-centric approach to care, as Carl said, which means, you know, we're not just out there to get patients to lose an x amount of pounds, but to lose sufficient weight to treat and prevent the complications of the disease. And this complication-centric approach has even found its way into the way Pharma does phase three clinical trials where, you know, weight loss isn't always the primary outcome measure. It's now it's become specific complications in related diseases have become the primary outcome measures, you know, whether it's sleep apnea, our cardio protection, our mash, our diabetes prevention. These have been tested as primary outcomes. And this has allowed us now to higher arches of preferred drugs based on the complications that any one individual patient may have that sits before you. So now we can really, 2016, we couldn't do that. We didn't have the data. But now we have drugs that have been shown to be effective to treat, for example, a mash, both semagletide and tzerpatide. There's good clinical data showing that those drugs can reverse the or improve NAS histology and fibrosis in mash. And semagletide now has an FDA of indication for that. So that's just one example of several different complications where we've been able to is the higher arches of preferred medicines based on evidence. And that kind of goes into my next question. I wanted to talk more about pharmacotherapy. So the update highlights these hierarchies of preferred medicines geared towards complications, centric care. So Carl, how should clinicians individualize therapy choosing between medications like semagletide or tzerpatide and others, especially when managing people with specific obesity related complications like type 2 diabetes hypertension and sleep apnea? Yeah, I think and that's really where we need to focus of these efforts. And so if you look at, I think it's algorithm figure eight, we have these different obesity related diseases and complications delineated out and based upon the evidence we have for these different specific modalities, we have prediabetes metabolic syndrome to focus on diabetes prevention and a hierarchy using shades of blue like tzerpatide semagletide might seem very obvious because they have direct glycemic benefits, but they also result in the most amount of weight loss that we expect based upon data to achieve prevention and remission, but followed by the lagotide phenomentil pyramid and even orlostate and older medication. And then the obvious type 2 diabetes side for in similar fashion, but also mace prevention. So major adverse cardiovascular events Dr. Garvey Tim said that for example, semagletide is indicated for mace. It's also indicated for reducing mace and so it is certainly first line and somebody who has obesity with established ethyrosalorotic cardiovascular disease and then we have mace and we have a series of blood pressure lowering based upon the data, chronic kidney disease, you know now a lot of the data are in type 2 diabetes, but semagletide and tzerpatide have been shown to have substantial cardiorenal benefits in addition to heart failure, preserved ejection fraction. And then on the other side we have biomechanical obesity related diseases and complications including arthritis and obstructive sleep at nifer which tzerpatide has an FDA indication. Karla, just another point we made in our algorithm for hierarchies and preferred medicines is no we're in the middle of an amazing era of drug development for this disease, adiposity based chronic disease and this is changing all the time and we recognize the need to update these hierarchies in real time as data became available and that's the one thing and another thing is yes we have evidence basis that these medications can effectively treat these complications in related diseases, but a lot we know that weight loss from any intervention could could also benefit these complications. So no we're not saying you have to use these medications, but these are the drugs where we have an evidence base and they've been shown to be effective, but that's not to say other medications can't be effective too. Yeah and to that point we have a slide talking about response to therapy and weight loss targets that are expected to achieve those more important clinical benefits and so we talk about incomplete response where people are only achieving you know 5% weight loss or less 10 through 15% being a good response and over 15% because we know that that's achieving things like remitting sleep atnia, reducing cardiovascular risk, putting type 2 diabetes into remission, no matter which modality we use as long as we know that they have safety and efficacy data and we also have a slide for cost effective therapy as you know depending on any other those specific compelling indications. - Tim, where does surgery fit in now? How was that changed with the explosion of all these new medications? - You know, they have begun to close the gap with the amount of weight loss you can achieve with various bariatric surgery techniques. You know, I think there's always gonna be room for bariatric surgery. And what impresses me is the prevention of, you know, all cause mortality, cardiovascular disease mortality, MI. I mean, there's a meta-analysis showing bariatric surgery reduces hazard ratios by 50%. And compare that to like, you know, 15, 20% of glipone receptor agonist, 20 to 30% of statinist. You know, so the cardiovascular and life, longevity affects a bariatric surgery. That's what always impresses me. So if I have a patient that's, you know, on the upper level of BMI, 40 and above and they have diabetes on insulin and are poorly controlled with sleep apnea and they're tired and depressed and just not enjoying life. I mean, these are candidates for bariatric surgery. I mean, they can be transformational. So, and also, these medicines don't work in everybody. There's a large individual variation in efficacy. So we will need to have bariatric surgery in our armamentarium for sure. - Definitely. - And Tim, I was gonna ask you also that the algorithm emphasizes reducing weight bias and stigma and addressing internalized weight bias as part of obesity care. Can you talk about how clinicians can operationalize that in their day to day practice? - Yeah, you know, we're not used to doing that. I don't think many of us have been trained to doing that. And this was addressed in the ACE position statement about bias. Carl was the first author on that. Yeah, I think they're, I think it's important to kind of get a feel for that, for every patient that we have. Just by talking to them about how they feel about their disease, what they expect out of therapy, there are validated questionnaires where you can assess this, the weight bias internalization scale and the weight self stigma questionnaire. I mean, these are available online. But I think, you know, just talking to your patient and using the, you know, the five, just motivational interviewing techniques when you talk to them, these five A's, you know, ask, assess, advise, agree and assist. But, you know, just talking, you're being asking permission to discuss this, how they feel about their disease, how they, how they reflect on themselves, how they feel about themselves, and then just going from there and, you know, just making sure they know it's not their fault that this is a biologically driven process that generates and sustains an increased level of ediposity. And we're here to help them. And we want to talk about ways we can help them and just engage them epithetically and have a staff and office environment and engage them epithetically because they have been stigmatized by their contacts with social media and even their contacts with other when they seek health care and they'll are health care systems. So we can, we just need to try to reverse that. And of course, this is a bigger factor in some patients more than others. But we just need to be aware of that and assess that because if we don't and let whole therapeutic prescription may not be effective because you know, it might not get the uptake and participation of the patient that we need and they might just continue to blame themselves and I just have decreased self-efficacy. So this is really important to consider and Carl, you must have something to say about that. You were the first author on this. Yeah, I mean, I think what you just said was great because we have those questionnaires to assess it. But I think if people can look those up, look at our old statement and they just incorporate them into the discussions. Like you just said, if you let the patients talk to you, they will tell you that they have internalized weight bias essentially. I mean, how often do we have people literally blame themselves or they talk about how they've been blamed and they think it's their fault, like you just said. And then when we teach them about the biological processes and give them some therapies and some support in addition to their lifestyle effort, then they realize, oh, it's not my fault. And by the way, the internalized weight bias really stems from external bias that we have in society. It's when the patients internalize that and that turns into that self-blame. And you mentioned that the efficacy, we know that people struggling with internalized weight bias have poorer outcomes. And so we have to address it and use our psychological colleagues, our behavioral health, support if we can and address this with patients. And they appreciate it in my personal experience. They really appreciate it when we acknowledge it and teach them about it and then treat them. They often come back and say, wow, I didn't realize it. It wasn't my fault. Now I'm doing well or whatever it is. I find that it's much easier now to talk to people about obesity. Generally, I think with all the medications that are available now, it's just sort of out there, constantly being discussed and advertised. But I have fallen to the trap of assuming that somebody wanted to talk about weight loss. And was sort of surprised when the individual was not expecting to have that conversation. So, Carl, any recommendations for how to broach the topic of management of obesity without making assumptions about an individual? Yeah, that's interesting. I think Tim mentioned the five A's, where you ask permission and that sort of thing. I think we specifically are often in a different position where people are generally referred either for obesity or maybe more often in your case, like for obesity related, say type 2 diabetes. And I think this, if we take the opportunity to discuss the true disease process and maybe use the term adiposity-based chronic disease as a bigger umbrella term for the overarching health of the person that just happens to be biologically driven causing excess adipose tissue, and not only just excess adipose tissue, but how the body deals with that excess adipose tissue. The cardiometabolic effects of the kind of the sick fat we talk about that adiposopathy term that some people use that drives the insulin resistance and ultimately the type 2 diabetes. And we frame it in a biologically sound disease method. I think they tend to understand that better and get away from that sort of weight-centric. The whole point of this concept is really that it's a health-centric approach, and it's not just weight or BMI-centric. It's truly the overall, what's on the inside that counts. I tell people, that's what we care about. What harm is it doing or what harm may it be causing in the future? If I could add a little bit about this diagnostic term adiposity-based chronic disease, ABCP. It tells you-- you just use the term obesity. It's a diagnosis based on BMI. Adiposity-based chronic disease is just more medically meaningful and actionable. It tells you what we're treating. Adiposity-based abnormalities in the mass distribution and function of adipose tissue. And why we treat it? It's a chronic disease, like other chronic diseases. It's life-long. There's complications that impair the quality of life and confer morbidity and mortality. And that's why we treat it. And this diagnostic term has been embraced by both ACE and the European Association for Study of Inhabicity. And whether you use that as a diagnostic term or just conceptualize the disease in that way, it entranges kind of a complication-centric approach to care. I mean, that's where you have to go if you conceptualize the disease in concert with that diagnostic term. So this is another ACE position statement and was picked up by the ESO. So we just hope that that promotes this complication-centric approach and health-centric approach, as you said, stated it, Carl. It's important, I think, that we as endocrinologists and members of the Endocrine Care Team use this terminology too when we're taking care of our patients and talking to other clinicians. I want to ask a question about the, you know, and the question is, what key message should clinicians take away from this new algorithm when managing patients with obesity or ABCD and everyday practice? So I think, again, going back to that overarching ABCD concept, we want to evaluate, you know, screen and evaluate people for obesity and adepositivase chronic disease. And it's not just BMI. We want to examine them, use waste-or-conference, waste-to-hite measurements to help delineate that adepocity and the risk of the adepocity. You know, we talk more about body composition analysis now that we have more data to help support the diagnosis of excess adepocity. But more importantly, again, staging the severity of disease based upon the presence of obesity-related diseases and complication. That includes the internalized weight bias that we talked about because the more severe the disease requires the more intensive therapy and also potentially the more weight reduction that we need to achieve to improve the health of the patient or prevent the downstream complications. And then, you know, looking at individual medications and surgeries to help patients achieve those clinical goals that we care mostly about that do correlate with weight. But this is not a weight or BMI-centric disease. it's really the bigger picture. and then we have some more personalization within this. In addition to, we have a whole slide and section on nutrition and exercise and behavioral therapy and sleep as the foundation of what everybody needs to do to help treat these disease states regardless of the change in weight even. - I love that you brought that up. The importance of lifestyle, the changes, diet exercise and sleep, including sleep. Tim, what would you add as key messages that people should take away from the algorithm? - Well, I think Carl laid out the big points, but I just might fill in a few little details there. You know, I think the use of waste-to-hide ratio as a way to measure fat distribution that's highly tied to outcomes is really catching fire a little bit. It's been recommended by a number of professional organizations. And that's something we did in this algorithm. Wasn't there in 2016. And you know, you don't have to have adjustments for racial or ethnic groups or age or region. It's just if that ratio is above 0.5, that's indicative of high risk, regardless of who you are. So it's easier to use as a risk statement as part of your anthropometric evaluation of the patient. Second, the clinical evaluation, which is really the second part of the diagnosis, which tells you how that excess ediposity is affecting the health of the patient, is not like impossible, it's just a standard intake. You know, we outlined what was needed there in terms of physical exam and history and laboratory. And then other tests that were necessary to follow up, if there was an indication of a particular complication related disease. And just one final point that deals with the Lancet Commission on obesity, which is created a lot of dialogue, are the commission defined these entities preclinical obesity and clinical obesity. Preclinical obesity being a state of excess out of posity without complications, considered to be kind of a state of relatively preserved health where patients are active and CEOs of corporations and exercising and doing well without complications. And we're going to say they have a disease. Well, they definitely have risk of progressing. So, and then clinical obesity is patients that do have complications that are integral to the state of excess ediposity. They're because of that. You know, for example, osteoarthritis or metabolic syndrome or epatexetosis or hypovenilation. And so I think the problem there is if you can, you know, a state of excess ediposity is a disease or not. And of course, the commission said, yes, these patients do deserve therapy as needed to reduce risk. But the term eteposity-based chronic disease is an umbrella term that encompasses all of this. And I think, and that is a disease. So it's part of the disease progression. So I think it kind of resolves that conundrum. I was one of the commissioners and people say mean things to me at meetings. So I just wanted to lay that out there. Yeah, well, and I'm glad Tim brought this up. And I don't want to go too deep into this. But this has been very confusing to patients and clinicians alike because of some of the semantics and the definitions that they came up with. So for example, we have some colleagues, we meaning all of us, in cardiology who recently published some conceptualization of using the Lancet Commission framework. And they included a person with excess ediposity who has pre-diabetes. And because of the definitions, the way they laid them out, pre-diabetes was not included as a complication. Is that right, Tim? The triad of high glucose, high triglycerides, and low HDL, that was considered an obesity complication. Yeah, well, these guys, so they put down because of the way the definitions were that pre-diabetes itself was not. And that's kind of why we combine these obesity-related diseases and complications into a sort of a set term. Because to us, that is an advanced stage of adiposity-based chronic disease and requires a little bit more intensive therapy to then reduce that risk of progression to type 2 diabetes. Whereas stage one, we kind of would consider maybe that pre-clinical, but it is a disease state because of the increased risk of future disease. Having, you know, metabolically healthy obesity and you've done a lot of the work on this, is not a benign state. And the end-hane, so it's 16% of adults. Yeah. And then if you-- if you-- the deeper you dig, the lower that number probably is, you know? But that's not a benign state. And generally, when you follow this along, if people don't treat the disease of obesity or ABCD, then they do progress and have other related disease or complications. And it's not just cardiometabolic stuff. It's the sleep apnea. It's the obesity-related malignancies that we think we can reduce the future risk of. And so stage one in our algorithm is not a benign state. It just isn't as advanced of a disease state. Carl, looking ahead, what do you see as the next frontier in obesity management? Are there upcoming therapies or areas of focus that you think will further transform care in the coming years? Oh, yeah. And I know somebody who's been lead author and other authors on some of these new medications, Tim. So there are some really cool things coming out. Tim's been involved in some of the research, some recent publications this past year with hopeful FDA approval in the coming years that hopefully will not only provide more options, but maybe some cost reduction. So there's going to be some oral therapies, the GLP-1 therapies, different combinations, triple agonist therapies, antagonist therapies, monthly versions, other combinations. In addition to the surgical therapies we have, and I think like Tim said, we still have to consider those, especially when we talk about cost effectiveness too. And everyone's different. You know, but I think we're going to have many multiple drugs that can produce upwards of 20, 22, 23% weight loss. And I think the field of battle is no longer efficacy. It's tolerability. And why should our patients have to be sick to their stomach for the privilege of having their disease treated? And all this is how I've been thinking more lately. And then if you consider it, we don't treat this disease very well at all. When you consider from real world data after a year, less than 50% of patients remain on the medication. When we know they have to stay on the medication to sustain the weight loss and the health benefits. So we've got a long way to go. You're right, Carl, it's an explosion of new medications and built around nutrient regulated satiety hormones and different combinations. But a lot of our patients don't need 20, 25% weight loss. 10 to 15% weight loss is what they need to achieve health benefits. It can be unhealthy to lose more weight. And sometimes we do them a disservice. So I'm still looking for a medication. It gives me 15% weight loss. It's really well tolerated that's accessible and affordable. And we just don't have that. So it's an amazing era this is, it's a drug development. We still have some pieces of the puzzle that are missing. An exciting time, but there's certainly more to do. Well, thank you both for joining me today. This 2025 ACE UBC algorithm provides an updated evidence-based framework for person-centered and complication-centric care, helping clinicians tailor treatment to improve health and quality of life. To read the full algorithm, visit pro.ace.com/clinical-guidance. Thanks for listening to another great ACE podcast. Join us for another episode at aac.com/podcasts and help us in our mission to elevate clinical endocrinology. Together, we are ACE.