Speaker 1:

Welcome to AACE 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 aace.com/podcasts. And now let's meet the endocrine experts who will be talking with us today.

Dr. David Lieb:

Hello and welcome to our AACE Podcast focused on AACE guidance documents. I'm Dr. David Lieb, 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 AACE algorithm for the evaluation and treatment of adults with obesity/ adiposity based chronic disease, the latest update to AACE's clinical guidance on obesity management. Joining me are Dr. Karl Nadolsky, chair for the Algorithm Writing Group, and Dr. Timothy Garvey, the committee vice chair. Thank you both for being here today.

Dr. Karl Nadolsky:

Thank you.

Dr. Timothy Garvey:

My pleasure.

Dr. David Lieb:

Dr. Nadolsky, can you start by introducing yourself, including your background in obesity medicine and endocrinology?

Dr. Karl Nadolsky:

Yeah, 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 AACE obesity experts, including Dr. Garvey, and they took me under their wings and helped continue my training and also involvement in some of the early renditions of AACE 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 kind of corporate healthcare to starting my own practice here in Holland, Michigan.

Dr. David Lieb:

And Dr. Garvey.

Dr. Timothy Garvey:

Yeah, thanks, David. I'm endocrinologist and professor at the University of Alabama at Birmingham. I've been in academic practice and research 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 phentermine/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 kinds 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 AACE. It really provided a platform for the 2016 guidelines for clinical management of obesity and other position statements, et cetera, and this our most current algorithm as well. That brings me to the present, David.

Dr. David Lieb:

Well, let's start with an overview. Karl, why was it important to update the 2016 AACE obesity algorithm and what major changes in science or practice prompted this 2025 update?

Dr. Karl Nadolsky:

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 matter 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 here.

Dr. David Lieb:

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?

Dr. Timothy Garvey:

Yeah, I think the 2016 guidelines was really the first guidelines to explicitly recommend a complication centric approach to care, as Karl said, which means we're not just out there to get patients to lose 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 III clinical trials where weight loss isn't always the primary outcome measure. Now it's become specific complications and related diseases have become the primary outcome measures, whether it's sleep apnea or cardio protection or MASH or diabetes prevention.

These have been tested as primary outcomes, and this has allowed us now to hierarchies of preferred drugs based on the complications that any one individual patient may have that sits before you. So 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, MASH, both semaglutide and tirzepatide. There's good clinical data showing that those drugs can reverse or improve NAS histology and fibrosis in MASH. And semaglutide now has an FDA indication for that. So that's just one example of several different complications where we've been able to hierarchies of preferred medicines based on evidence.

Dr. David Lieb:

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 complication-centric care. So Karl, how should clinicians individualize therapy choosing between medications like semaglutide or tirzepatide and others, especially when managing people with specific obesity-related complications like type II diabetes, hypertension and sleep apnea?

Dr. Karl Nadolsky:

Yeah, I think, and that's really where we need to focus 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 pre-diabetes metabolic syndrome to focus on diabetes prevention and a hierarchy using shades of blue, like tirzepatide, semaglutide 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 liraglutide, phentermine/topiramate and even Oralistat, an older medication, and then the obvious type II diabetes side in similar fashion, but also MACE prevention, so major adverse cardiovascular events. Dr. Garvey, Tim said that, for example, semaglutide is indicated for MASH, it's also indicated for reducing MACE. And so it is certainly first line in somebody who has obesity with established atherosclerotic cardiovascular disease. And then we have MASH. 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 II diabetes, but semaglutide and tirzepatide have been shown to have substantial cardio renal 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 apnea for which tirzepatide has an FDA indication.

Dr. Timothy Garvey:

Karl, just another point we made in our algorithm for hierarchies of preferred medicines is 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 and related diseases, but we know that weight loss from any intervention could also benefit these complications. So now 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.

Dr. Karl Nadolsky:

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 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 apnea, reducing cardiovascular risk, putting type II 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 depending on any other of those specific compelling indications.

Dr. David Lieb:

Tim, where does surgery fit in now? How has that changed with the explosion of all these new medications?

Dr. Timothy Garvey:

They have begun to close the gap with the amount of weight loss you can achieve with various bariatric surgery techniques. I think there's always going to be room for bariatric surgery. And what impresses me is the prevention of 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 15, 20% of GLP-1 receptor agonist, 20 to 30% of statins. So the cardiovascular and life longevity effects of bariatric surgery, that's what always impresses me.

So if I have a patient that's in 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. 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.

Dr. David Lieb:

Definitely. And Tim, I was going to 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?

Dr. Timothy Garvey:

Yeah, 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 AACE position statement about bias, and Karl was the first author on that. Yeah, I think it's important to 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 just talking to your patient and using just motivational interviewing techniques when you talk to them, these five A's ask, assess, advise, agree and assist, but just talking, maybe asking permission to discuss this, how they feel about their disease, how that reflects on themselves, how they feel about themselves. And then just going from there and 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 adiposity, and we're here to help them.

And we want to talk about ways we can help them and just engage them empathetically and have a staff and office environment and engage them empathetically because they have been stigmatized by their contacts with social media and even their contacts with other when they seek healthcare and our healthcare system. So 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, our whole therapeutic prescription may not be effective because we 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 Karl, you must have something to say about that. You were the first author on this.

Dr. Karl Nadolsky:

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 then just incorporate them into 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. 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 and now I'm doing well." Or whatever it is.

Dr. David Lieb:

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 into 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 Karl, any recommendations for how to broach the topic of management of obesity without making assumptions about an individual?

Dr. Karl Nadolsky:

Yeah, that's interesting. I think Tim mentioned the five A's where you ask and 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 II diabetes. And I think 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 sick fat.

We talk about that adiposopathy term that some people use that drives the insulin resistance and ultimately the type II 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?

Dr. Timothy Garvey:

If I could add a little bit about this diagnostic term, adiposity-based chronic disease, ABCD, it tells 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 lifelong. 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 AACE and the European Association for the Study of Obesity. And whether you use that as a diagnostic term or just conceptualize the disease in that way, it entrains, engenders 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 terms. So this is another AACE position statement and was picked up by the ESO. So we just hope that that kind of promotes this complication-centric approach and health-centric approach as you stated it, Karl.

Dr. David Lieb:

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 of both of you now, and the question is, what key messages should clinicians take away from this new algorithm when managing patients with obesity or ABCD in everyday practice?

Dr. Karl Nadolsky:

So I think, again, going back to that overarching ABCD concept, we want to screen and evaluate people for obesity and adiposity-based chronic disease. And it's not just BMI. We want to examine them, use waist circumference, waist-to-height measurements to help delineate that adiposity and the risk of the adiposity. We talk more about body composition analysis now that we have more data to help support the diagnosis of excess adiposity, 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 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 too, 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.

Dr. David Lieb:

I love that you brought that up, the importance of lifestyle changes, diet, exercise, and sleep, including sleep. Tim, what would you add as key messages that people should take away from the algorithm?

Dr. Timothy Garvey:

Well, I think Karl, you laid out the big points, but I just might fill in a few little details there. I think the use of waist-to-height 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 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 adiposity is affecting the health of the patient is not like impossible... And it's just a standard intake. 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 has created a lot of dialogue. The commission defined these entities, preclinical obesity and clinical obesity.

Preclinical obesity being a state of excess adiposity 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. And then clinical obesity is patients that do have complications that are integral to the state of excess adiposity there because of that. For example, osteoarthritis or metabolic syndrome or hepatic steatosis or hypoventilation.

And so I think the problem there is if a state of excess adiposity 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 adiposity-based chronic disease is an umbrella term that encompasses all of this, and that is a disease. So it is 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.

Dr. Karl Nadolsky:

Yeah. 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 adiposity who has prediabetes. And because of the definitions, the way they laid them out, prediabetes was not included as a complication. Is that right, Tim?

Dr. Timothy Garvey:

The triad of high glucose, high triglycerides and low HDL, that was considered an obesity complication.

Dr. Karl Nadolsky:

Yeah. Well, these guys, so they put down because of the way the definitions were that prediabetes itself was not. And that's kind of why we combined 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 II diabetes. Whereas stage one, we would consider maybe that pre-clinical, but it is a disease state because of the increased risk of future disease. Having metabolically healthy obesity, and you've done a lot of the work on this, is not a benign state.

Dr. Timothy Garvey:

And it's 16% of adults.

Dr. Karl Nadolsky:

Yeah. And then the deeper you dig, the lower that number probably is. 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 diseases 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.

Dr. David Lieb:

Karl, 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?

Dr. Karl Nadolsky:

Oh yeah. And I know somebody who's been a lead author and other authors on some of these new medications, Tim. So there's 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 reductions. There's going to be some oral therapies, 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.

Dr. Timothy Garvey:

But I think we're going to have 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. Why should our patients have to be sick to their stomach for the privilege of having their disease treated? That's how I've been thinking more lately. And then if you consider, 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, Karl. 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 that gives me 15% weight loss that's really well tolerated, that's accessible and affordable, and we just don't have that. So it's amazing era, this sort of drug development. We still have some pieces of the puzzle that are missing.

Dr. David Lieb:

An exciting time, but there's certainly more to do. Well, thank you both for joining me today. This 2025 AACE obesity 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.aace.com/clinical-guidance.

Speaker 1:

Thanks for listening to another great AACE podcast. Join us for another episode at aace.com/podcasts and help us in our mission to elevate clinical endocrinology. Together we are AACE.