The New Era of Weight Loss and Heart Health with Robert Eckel

James Hill:
Welcome to Weight Loss And, where we delve into the world of weight loss. I'm Jim Hill.

Holly Wyatt:
And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and live your best life while you're doing it.

James Hill:
Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

Holly Wyatt:
Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

James Hill:
Ready for the “And” factor?

Holly Wyatt:
Let's dive in.

James Hill:
Here we go.

Holly Wyatt:
Jim, if I ask people what disease scares them the most, I think many would probably say cancer.

James Hill:
Yep.

Holly Wyatt:
But statistically, heart disease remains the leading cause of death in the United States. And what's interesting is that most people don't naturally connect obesity and heart disease. I think they think about their weight, and I think they connect diabetes, blood sugar, but not necessarily their heart.

James Hill:
Yeah, Holly, and for a long time, medicine didn't connect those dots either. Obesity was viewed as a risk factor, maybe something that increased the likelihood of other diseases, but not necessarily a disease affecting the cardiovascular system itself.

Holly Wyatt:
That thinking has changed dramatically. And today we have evidence that treating obesity doesn't just lower your weight. It can reduce heart attacks, reduce strokes, and reduce major cardiovascular events.

James Hill:
Which raises an important question. What took us so long to get here? And what does this new era mean for people living with obesity? Holly, today's guest has spent his career at the center of those questions. It is my absolute pleasure to welcome an old friend. Now, I'm not saying he's old, but he is.

Holly Wyatt:
But he's my friend, too, though.

James Hill:
Yeah, he is.

Holly Wyatt:
Okay.

James Hill:
Dr. Robert Echol is Professor Emeritus at the University of Colorado Anschutz Medical Campus and one of the most influential voices in cardiometabolic medicine over the last four decades. Holly, Bob is a dear friend, but he's also one of the researchers that I admire most. And you and I had the pleasure of working with him for many years at the University of Colorado. Bob is uniquely qualified for this conversation. He is the only person who has served as president both of the American Heart Association, the American Diabetes Association, and the Obesity Society. Think about that. Heart, diabetes, obesity, three disciplines that have really kind of been separate over the years. He's been president of all of them. This is an accomplishment that will probably never be repeated. Bob's work has shaped how physicians think about obesity, metabolic syndrome, diabetes, lipids, and cardiovascular disease.

Holly Wyatt:
And what I appreciate the most about Bob is that he hasn't simply watched the field evolve and reported about it. He's helped lead it. He shaped it. He remembers how obesity was viewed in the 1980s. He remembers all the debates that we had about metabolic syndrome. He remembers when cardiologists didn't see obesity as something that was really part of their job. And now he's watching one of the biggest shifts in obesity treatment any of us have ever seen in our careers.

James Hill:
Bob, what a pleasure to welcome you to Weight Loss And.

Robert Eckel:
Well, Jim and Holly, those are very kind words, and I feel really humbled and honored by everything you've said. It's been fun, and that passion still exists. And despite being formally retired, getting no paychecks from the University of Colorado School of Medicine anymore, I call myself rewired because I'm still pretty active. I'm rewired for several reasons. One, I can learn more. The more you learn, the more you realize you don't know. And then secondly, I think, is the fact that there's sometimes you're asked to do something, you feel like you can contribute. So I think those two things keep me going. And it's really a great privilege and pleasure to be involved still at sometimes a national and international level. So great comments. Thanks so much, guys.

James Hill:
Sure. So you and I met, Bob, sometime probably in the 80s. And think about that. If we had been together, say, in 1980, and someone had said by 2026, we'd have a medication that reduces cardiovascular events by 20% in people with obesity, what would you have thought?

Robert Eckel:
Well, I'm not sure I want to be a historian here, Jim, but let me cut to the chase. In 1982, I was privileged to be a very junior member of a lot of obesity science-related icons. And I'll mention names, but your audience doesn't need to hear those. But all that aside, we met at Vassar College. There were 40 of us. And we formed an organization called the North American Association for the Study of Obesity.

Robert Eckel:
Okay. It wasn't, we had no drugs really that were effective. Lifestyle was the only approach. But it was the science behind body weight regulation. And Holly and Jim, you guys have contributed so much about issues that relate to obesity and weight maintenance and why people regain weight after they've lost weight. And your contributions are endless in this space. But anyway, that organization was formed for the study of the science of obesity or excess body weight. And we weren't talking about treatment so much. We were just talking about how energy balance is controlled, what makes people eat more, what makes people more sedentary, et cetera. And that then evolved to our relationship in the late 80s. And I'll cut to the chase, Jim. When I came to Vanderbilt as a visiting professor, maybe an assistant or associate professor at that time, I met you for the first time and really kind of was admiring what your work was doing at that time, the whole room calorimetry. And I thought that was going to be something that we needed Jim Hill at Colorado for. So your recruitment really related to a lot to the momentum I created at the university to get you recruited. And I'm so glad I did.

James Hill:
You were a big part of that. And we had many, many good years together, Bob.

Robert Eckel:
A lot of fun, Jim. A lot of fun.

James Hill:
So, tell us a little about your background. You're an endocrinologist, but you were one of the first people to begin sort of connecting diabetes, heart disease, and obesity. Tell us a little about how that interest evolved.

Robert Eckel:
Well, Jim, good question. I think it related to my being invited to be part of the nutrition committee at the American Heart Association. This was in the mid-90s. And I was asked, why am I being asked? I mean, lipids and lipoproteins have always been the focus of my research, both at the basic science level and clinically. And of course, the lipid metabolism very much relates to body weight regulation directly in many ways indirectly. But all that aside, I wasn't sure why I was being asked. And they told me that they were aware that I was doing research in both basic science experiments and in clinical subjects with excess body weight or with living with obesity. And so that was the reason they invited me. And I think, so the AHA was starting to crack the door open a little bit about maybe obesity, something they should begin getting concerned about. And Holly and Jim, you guys remember these maps are starting to be developed in kind of the early nineties. And these maps were changing in front of everybody's eyes in terms of the prevalence of overweight and obesity in the United States. So they brought me on board more for obesity science. Back to NASO, right? I mean, the Obesity Society name didn't change for another couple of decades, but NASO was the study of obesity. And so, even though clinically we didn't have effective pharmacotherapy at that time, that's the story, Jim, in terms of why the AHA got interested in biomedical.

Holly Wyatt:
Yeah. So, I remember you chaired the AHA scientific statement where you made a case that obesity isn't just a risk factor. It's a disease that directly damaged the cardiovascular system. Tell us a little bit about that. Was there resistance to that? I mean, I think now when we see where we're going, it all makes sense. But back then, I think it wasn't as clear for everybody.

Robert Eckel:
Well, Holly, the course that kind of was outlined at the AHA ended up with a statement which was called a call to action that Ron Krause from Berkeley and I co-authored and published as a kind of an editorial perspective in circulation, meaning the American Heart Association says obesity is important to cardiovascular disease. Then that evolved into a more complicated multi-authored paper that really talked about how obesity relates to cardiovascular disease. Going beyond a low HDL, high triglycerides, high blood pressure, glucose intolerance, etc. And Jim, as you mentioned, that evolved into the metabolic syndrome where I got very involved in the definition of the metabolic syndrome internationally.

James Hill:
Well, a lot of people use the term, Bob, cardiometabolic health. What do you think? Is that a good way to talk about the stuff that you're interested in?

Robert Eckel:
Well, Jim, that really has a foundation in obesity, and obesity leads to glucose intolerance and insulin resistance, and the whole issue of the relationship to heart disease is really what the metabolic syndrome was kind of all about initially. And this term cardiometabolic, I remember there was a tremendous controversy over the term, what does it mean and what does it encompass? And so that term kind of bounced around for about five years, and then I think once the metabolic syndrome got finally defined the best as possible in the early 2000 era, then cardiometabolic medicine became an entity. And I'll just comment briefly on where that's at now. So cardiometabolic medicine is not only the heart and metabolic diseases, such as glucose intolerance, diabetes, and obesity, but ultimately includes the kidney, includes the liver, and we think it includes the central nervous system also. And that relates to an ongoing activity that I'm involved with people from Europe and in Asia also.

Holly Wyatt:
I want to kind of bring it to current stuff that I know our listeners want to talk about. I think about the SELECT trial a little bit more and how that's changed the field. And I think it's going to change the field kind of moving forward. So can you tell us a little bit about the SELECT trial and how you think it's impacting the field now. And I think it makes sense. It's coming from what you've studied. And now we're here. And how is that going to impact where we go almost?

Robert Eckel:
Well, a SELECT trial was carried out on a large number of subjects, and I want to be perfectly accurate. This is 17,600 subjects were treated or untreated with a drug called semaglutide at a dose that we consider clinically a high dose. At least at that time, it was a high dose at 2.4 milligrams. This study was carried out over four years, and Holly, you alluded to the fact that this is really the first clinical trial ever done looking at an agent that can produce substantial weight reduction and hopefully modify the natural history of cardiovascular disease.

Robert Eckel:
So that's the study design, and people were well-matched, whether they were randomized to the drug semaglutide or whether they were given an injection of no substance or the so-called placebo group. That study was carried out over a period of, again, four years, and there was a benefit of a reduction of the primary endpoint, which was all-cause cardiovascular disease, including myocardial infarction, et cetera. There are a lot of other outcomes that were part of that composite endpoint, and that reached highly statistical significance. So that was the first trial ever to be done looking at a drug causing weight reduction in people with obesity and not diabetes. Most of the previous trials had included people with diabetes. And the reason for that discrepancy has been important because glucose intolerance leading to impaired glucose tolerance, or, if you will, pre-diabetes. Now, importantly, then ultimately, diabetes has a lot more risk for cardiovascular disease. So the trials were all done to reduce weight in those subjects and proven to be positive. Several trials before the SELECT trial. But to just conclude, the SELECT trial was the first one done with effective weight reduction due to a pharmacotherapy that proved to be successful.

Holly Wyatt:
Yeah, and independent of diabetes, because you can't untangle it. When you study it in diabetes, it's very hard to untangle. So what reduction? It was, I think, about a 20 percent. Am I remembering correctly?

Robert Eckel:
Perfect. 20%. And the interesting thing about the study, and I think our audience may be interested to know this, is the weight reduction was really not the powered outcome. In other words, that wasn't the outcome. It was the waist circumference. And the reason for the waist circumference is that, Jim, how you guys know this. So, I mean, everybody knows this pretty much now who practice medicine, but how much weight you put centrally around your waist really relates importantly to cardiovascular disease risk. And that includes risk for diabetes, for high blood pressure, for lipid disturbances like high triglycerides, etc. So losing your weight around your waist is preferential for the outcome. And that proved to be successful. But the thing is, and this has been seen in other trials using this class of drugs, semaglutide or another agent made by another company called tirzepatide. Ultimately, the outcomes are not entirely related to the weight reduction or the amount of reduction in the waist circumference. So that opens up really a big black box as to how these drugs are working beyond that that impact risk factors, including waist circumference, but now have other effects that are poorly understood. It's not blood pressure. It's not inflammation. It's not other things that contribute and may be changed by the drug, but they don't adequately explain the benefits. So, a lot of science to be done yet, Holly and Jim. We need to keep our eyes open to what occurs in the near future.

Holly Wyatt:
And just for our listeners to translate it for them, this 20%, what it means is compared to the placebo group, people taking the semaglutide experienced about 20% fewer major cardiovascular events. That's huge.

Robert Eckel:
Well said.

Holly Wyatt:
I mean, is that a big number for you, Robert? I mean, Bob, do you think that's...

Robert Eckel:
Yes, I mean, just to compare it, the best of statin trials is around a 30% reduction. And the additional kind of cholesterol-lowering trials produce an additional 15% reduction.

Holly Wyatt:
There we go. Yeah, statins.

Robert Eckel:
That's powerful. That 20% falls within a very important range. Yes.

James Hill:
Bob, so your reminiscing took me back to the meeting at Vassar where you said there were about 40 obesity researchers. And, you know, that represented most of the obesity researchers in the U.S. There were a few more, but not many. Now obesity has really become such a big deal. And it's studied by diabetologists, cardiologists. Now cancer is playing a role, cognitive decline. This has got to be a little bit of a sense of accomplishment for you, because you were connecting these things way before anybody else connected them. When we were younger, Bob, nobody really wanted to study obesity.

James Hill:
Now everybody wants to study it. Talk about the future here. We have treatment options. We have people from different areas looking at this. What's your hope for the future here?

Robert Eckel:
Well, I think, in part, first of all, those are kind comments again, Jim. I don't think I deserve as much credit as you're giving me. I was part of a large team, both nationally and to some extent internationally. So to cut to the question, I think the work you and Holly have done for decades relate to strategies once people lose weight to keeping the weight off is so critically important. And you guys must be very interested in terms of this recidivism of weight regain when you stop these kinds of agents. You're injecting them. Of course, now we have two pills that have been approved that could be taken orally. And although those have been shown to be beneficial also in reducing cardiovascular disease events like a heart attack or a stroke or death from cardiovascular disease, those drugs are not cheap at this point in time. And secondly, we don't know whether stopping those is going to have the same effect on weight regain. Other than surgery, and I hope we're going to just touch base minimally on surgery.

James Hill:
Yeah.

Robert Eckel:
Surgery has been proven to be very effective in getting large amounts of weight lost. But then there's surgery. I mean, most people don't want to undergo the knife if they don't have to. And the drugs have been very proven to be beneficial. So why would I want an operation when the drugs work? But when the drugs are stopped, weight is regained. And so the strategies you've developed, Holly, I'm playing a major role in that with you, Jim. I think that, you know, I guess the weight control registry, Jim, which you had a lot to do with, you and Rena, et cetera. I mean, being physically active is incredibly important. We're not talking about walking around the block once or twice a week. I mean, we're talking about being really active. But I think nutrition has a role to play there in weight regain. So I'm kind of not answering your question. But I think the whole regulation of body fat, and I'm going to say something, and I want you guys to comment on this. You know, the feeding studies of Claude Bouchard were very telling and that there's a genetic risk for weight regain when you overfeed people a lot of calories. But after those people quit eating a lot, what was that, a six-month study, Jim?

James Hill:
Something like that. Yeah, I think it was.

Robert Eckel:
They gained like 20 pounds. But over the next six months to a year, they all lost, almost everybody lost back to their original weight. So I think our public needs to understand that weight gain to a certain level occurs over years to decades. And once you reach some sort of a weight, I think the brain kind of knows the body composition in terms of the amount of adipose tissue that's present, and you defend that. And so one of the areas of science is understanding how the brain senses fat. And I think it senses fat. I don't know that it senses lean tissue. I think it senses body fat. And there are lots of reasons, teleologically, why it does that. I mean, we can talk more about the importance for reproductive science and women menstruating and ultimately being able to get pregnant and lactating and all that's very important for body fat. And I don't know if I remember this correctly, I don't think you contributed to this, Jim. This was kind of about the time you were recruited. But in 1992, I published a book on obesity, a book. Books don't sell. Nobody reads them.

James Hill:
Tell me about it.

Robert Eckel:
The first chapter was on why body fat's beneficial when you don't have enough food. So, to think that obesity is always harmful is not true either. Obesity can be beneficial if you're living in situations where the food is not adequate. So that's a long answer.

James Hill:
Wow, boy, there's so much to impact there, Holly. So I want to hit on a couple and then I'll let you do it. Bob, I couldn't agree with you more. I think there's a time, an amount of obesity, a duration of obesity that sort of resets the level at which the body is regulating. And that would actually speak for early treatment or even prevention, because I think people that have been obese for a while are always going to pay that price for having been obese.

Robert Eckel:
So, Jim, just to build on that, I don't want to lose the thought, is that prevention of excess weight gain is the most important public health problem, I think, in the world right now. I mean, yes, we have infection. We have starvation. I mean, there's war. There's all kinds of other issues. But in terms of chronic disease management, we need to prevent excess body weight gain.

James Hill:
Holly, I'm loving this. So, Bob, my question then, are the GLP-1 drugs helping or hurting for prevention?

Robert Eckel:
Well, how about doing a trial and families with a high risk of obesity and starting these agents maybe during teenage years or something? I don't know. That's wild and crazy.

James Hill:
Well, what about even epigenetics? We haven't tested them in pregnancy, but if you could safely prevent weight gain in pregnancy, so there's so much research that could be done here. But I want, Holly, before I let you talk, I have one more point I want to make here. Because again, Holly and I have always been really lifestyle, lifestyle modification. But we welcome these meds, Bob, because they can get the weight off. And I believe that very soon there's going to be a medication that will help anybody who wants to reach their goal weight. Now the question becomes how you keep it off. And that's where I think lifestyle is going to be really synergistic with the medications in terms of the long run. You have to look at nutrition. You have to look at physical activity. You have to look at mental health. And if we can get the weight loss over here, which everybody wants, maybe now we can focus on some of the more important long-term things, keeping it off and helping people actually be happier with their weight.

Holly Wyatt:
All right. Do I get to say something? Can I talk now?

James Hill:
You can talk now, Holly.

Holly Wyatt:
Thank you. I'm joking with you. So I like what you said, Bob. You talked about not all obesity is bad. I mean, there's a certain reason why we want to store body fat. There's a certain reason, and we can look back on that. When I look at these drugs now, what I think about is the new semaglutide, tirzepatide, the GLP-1s, they have come out and have really just taken the appetite and pushed it all the way down to this level where it's not, in some people being regulated at all. It's just super low. And that really changes the whole system. And so is that a good thing? That's the question, you know. And if you do stay on these drugs for long periods of time and you keep the appetite low, then maybe this reset that you're talking about in the brain or this level that the brain is sensing, because you, you know, pharmacotherapy has kept the intake so low, you've kind of taken that out of the picture.

Robert Eckel:
Well, that's wishful thinking and maybe hopeful thinking. It'd be great if that were true. I have a sense that once people develop a steady excess body fat, they will maintain it lifelong. I think ultimately this is an adaptation that maybe cannot be changed. The other thing I just saw, which you guys will like, I didn't look at the paper, but I saw the headlines of the paper stated in multiple different venues yesterday online about people on GLP-1 receptor agonists. I'm generalizing the type of drug people are using are less active when they're on the medication. So is that a behavioral change that is a sustained behavioral change? And if they do stop the drug, by the way, the weight regain doesn't occur within a month or two. I mean, it takes three to five years, but they do tend to come back to this baseline weight. So you guys know better than anybody when people lose weight, if you let them go, they come back to the kind of that baseline weight. Holly, this is the set point. And your question's a good one. Can that be permanently changed?

Holly Wyatt:
By staying on the drug, like a statin. You'd stay on the statin forever. If you stay on the GLP-1 forever, are you going to regain on the drug? Do you think you'll regain on the drug, or do you think the drug is going to be powerful enough to keep this set point from coming back?

Robert Eckel:
Well, I think as long as you're on the drug, unless there's some receptor, I mean, for the audience in general, drugs work by binding the cell services that signal downstream events that make the appetite reduce. So these drugs reduce appetite by binding in the brain to certain cells. And so when you’re on the drug, these cells create a single series of hormones in the brain that reduce your appetite. So we all know that pretty well based on the basic science of these agents. Now, if you continue on these drugs long-term, does that signaling from these drugs decrease? In other words, do they work less well? And I don't think we have any evidence for that right now. So, Dr. Wyatt may be ringing a bell that's going to be ringing more loudly as we go forward to think that possibly over time that system could change. And I think at this time, we don't have any evidence it would. So in general, when I, as a clinician, lowered cholesterol, I need to keep the people on the statins or other cholesterol-lowering drugs. When I treat diabetes, unless they have a fair amount of weight loss, they need to be treated for their diabetes. And I think weight is the same. If weight loss per se, in addition to all the other things that go with excess weight, is being controlled by medication, that needs to be continued. So I've been part of the Lancet Commission, which is redefining how we approach obesity diagnostically.

Robert Eckel:
That whole work that we published recently in the Lancet has been highly controversial. But our goal there wasn't to look at the treatment of obesity. It was simply looking at how we define excess body weight. But as part of that, really, I think we need to go beyond BMI. And I think our public has heard this term BMI, and that's basically a relationship between your weight and your body mass surface. And so that is a calculated level that predicts excess weight. But I think we've said we need to go a little bit further in defining obesity to begin with.

James Hill:
We welcome these medications as welcome new tools, Bob. And I think there are a number of options. We're very supportive of people that want to go on the meds and stay on them chronically. I think there's still a benefit of nutrition and physical activity, even if you're on the meds. If you go off the meds, it's absolutely essential that you do that. And I think we're going to figure out some combination of long-term use of medications intertwined with lifestyle. You know, people are already experimenting. Holly says the clinical approach is outweighing the science. People are looking at intermittent use and lower doses and all that. And we don't have any evidence of effectiveness, but a lot of stuff is being tried out there. So to me, these are wonderful new tools, and we have to figure out the best way to use these tools in the future.

Holly Wyatt:
I want to talk about guidelines a little bit, because I know you've been involved in so many of the guidelines. And I was just thinking, if the new SELECT study that we just talked about with that 20% reduction in cardiovascular risk, if that had come out as a statin trial, would the guidelines have been rewritten really quickly. And do you think the guidelines will be rewritten with GLP-1s, kind of replacing or as part of statins, thinking of them like statins?

Robert Eckel:
Well, I think the comment on guidelines, in general, the level of evidence that relates to a guideline modification comes in a wide variety of flavors in terms of how many randomized controlled trials have been done, how well controlled are they, and down the line of level A, grade A1, et cetera, in terms of rating the benefit of an intervention on the guideline statement. And I think the answer is yes. So you do one very well controlled trial, guidelines can be changed. And I can speak for the medical standards of care for the American Diabetes Association, that this is incorporated into their guideline now. So, yes, I think the answer is yes. A well-done randomized control trial, one, is enough to change the guideline. Yes.

Holly Wyatt:
All right. So do you think cardiologists will be prescribing GLP-1s like they prescribe atorvastatin or one of the statins?

Robert Eckel:
Well, I think that's coming along. The cardiology prescriptions five years ago were minimal, but they're going up logarithmically. And the reason they're going up, Holly, is because of trials like SELECT. I mean, the idea of losing body weight in terms of the benefit for overall health is there. There's a hint that it may ultimately benefit other addictive behaviors. And you guys know well that there's a certain amount of science and body weight regulation that relates to the addictive nature of certain types of food intakes over time. So, addictive behavior that goes beyond simply selection of certain foods is maybe favorably modified by these agents. So, in general, but cardiologists are impressed by one thing primarily is does it affect heart disease, stroke, and death from cardiovascular disease.

James Hill:
Well, Holly, we have a lot of questions for Bob. You want to get to some of the listener questions?

Holly Wyatt:
All right. Let's get to those.

James Hill:
Okay. I'll start. Here's one, Bob. I'm 62. I've been on statin for 10 years and my new doctor wants to add a GLP-1 because of my weight and family history. I'm scared of being on two medications for the rest of my life. What would you tell me?

Robert Eckel:
Well, I'd like to have a conversation with you and your doctor, and that's one you can have with your doctor, to ask her or him what the reasons are that weight loss is important to you. I'd like to know a little bit more about your blood pressure. I'd like to know a little bit more about your lipid levels, how effective are the statins in modifying your lipids favorably. I'd like to know a little bit more about ultimately your weight history. Holly, you and Jim know well, the obesity evaluation clinically goes beyond simply what's your weight and what do we need to do about it? I mean, I think we need to know ultimately, what were your weight as you were growing up? What was the age of your first menstrual period? Ultimately, how many pregnancies have you had? How much weight did you gain? I mean, there are things about the history that reflect how long the weight excess has been there, what's been successful in the past in terms of a lifestyle attempt at weight reduction. So, these agents, again, remember, have benefits that go beyond simply the weight reduction. So, I'd like to know a list of your other risk factors and how they might be modified. Family history of diabetes would be enough to think you should be on it too, depending on, again, what your current level of glucose metabolism looks like.

Holly Wyatt:
So, what you just showed is there's a lot of questions to ask. It's complex. The medical management, there's a science, there's an art. It's never just an algorithm, so to speak, where I think a lot of people are sometimes maybe prescribing the drugs out there like this. The second question falls really really good one.

James Hill:
Wait, I want to follow up on this one, Holly, because this is important. So what you said is terribly important, Bob, but a lot of these medications are being prescribed by primary care docs, and primary care docs are terrific, but they're not necessarily trained in weight management. Can we train them to ask those kinds of questions when they're looking at prescribing the meds?

Robert Eckel:
Well, Jim, I think, first of all, I think the best doctor is the one who knows when to refer. I think that's the best doctor. And in primary care, the family docs, even in some rural settings, are still delivering babies. I mean, so...

James Hill:
That's right.

Robert Eckel:
These docs have to be incredibly capable to know, again, when to refer when things go beyond their capability. In a more urbanized setting where maybe your primary care physician is an internist, she or he should be able to ask more sophisticated questions. But keep in mind, Holly knows this well. In the clinic, you're pressured for time. There's just not a lot of time. And Holly, I know you were incredible with the clinic you had in Colorado. I'm sure that's true in Birmingham too. A good initial visit for a patient with excess body weight, living with obesity, is at least an hour. You can't do this in 20 minutes.

James Hill:
Yeah.

Robert Eckel:
And the kinds of questions I bounced out before very quickly are the kinds of questions that are important in understanding the individual patient. So, I think in general, I think we can get primary care physicians sufficiently engaged in how to work up people with excess body weight.

Robert Eckel:
But again, it's just time. Education's one thing, but time to do it's another. Holly, your thoughts?

Holly Wyatt:
Okay. I'm going to do the second question falls right in with this. This is why I wanted to go straight into it. And this is something that people are struggling with right now. So what do we tell people? So she says, my cardiologist won't prescribe a GLP-1. He says it's not in his scope. My PCP says she'll prescribe it, but she's never managed one. She doesn't have much experience with it. Who's actually supposed to be running this medication for somebody like me? And this is what's happening right now, you know, out there.

Robert Eckel:
Well, again, I'll repeat my common, if your physicians aren't comfortable with it, get a second opinion. Ask to be referred to the type of physician who can oversee your evaluation and therapeutic decision-making.

Holly Wyatt:
Yeah.

Robert Eckel:
Again, I can't tell you to whom to go and where you live, etc., so I'd have to understand the demographics of the area in which you live. But in general, I'm going to generalize this, you can certainly not necessarily go online here, but I think you can ask your physician who, in fact, might be good to take on this responsibility. And there's nothing wrong with a patient asking for a second opinion. You can do it very politely and still have faith in your underlying physician for decisions to relate to routine medical care. But there's nothing wrong with asking you to have a second opinion. And that's what I would encourage people to do.

Holly Wyatt:
Yeah, I agree with that.

James Hill:
All right, here's one. I had a heart attack at 49 with a BMI of 27. Everyone keeps telling me I'm not overweight enough to benefit from these medications. Is that right?

Robert Eckel:
No, that's not right. But the question comes up, what are the indications for the medication? And again, as I alluded to before, and I'll not go into detail, the Lancet Commission thinks we need more than a BMI. So you should have a waist circumference done. You could have a weight height squared ratio. In other words, there are other ways to assess excess body fat. So if those things do not define obesity, then the issue is, should you be on these agents or should you be treated more aggressively for other risk factors? But no, the agents work in people whose BMIs are 27. I would like to know more about these other measurements of excess body fat before you would prescribe the drugs. And I would also need to know your other risk factors and what might be favorably modified by these drugs.

Holly Wyatt:
Yeah, it's complex.

James Hill:
We're seeing a theme here, Holly.

Holly Wyatt:
Well, it's true.

James Hill:
You can't just prescribe the meds. You've got to understand the patient.

Holly Wyatt:
And it's so true. Here's one more. I lost weight. I kept it off for six years, and last year I had a stent placed. I feel like my body lied to me. Does keeping weight off actually help the heart, or did I do all that for nothing?

Robert Eckel:
Well, it's a straightforward question, and I don't know enough information to know exactly what was impacted by your weight loss. How much weight loss occurred, did she or he say?

Holly Wyatt:
No, I don't have those details here, but I think the idea is did a lot of work, lost weight, kept it off. And yet my cardiovascular, you know, it progressed. I had to have a stent placed.

Robert Eckel:
Well, the stent, why was it placed? I mean, was this a routine?

Holly Wyatt:
Well, let's just say I had a heart attack. Let's just, okay, let's not do the stent. Let's say heart attack. I had a heart attack.

Robert Eckel:
Well, look, atherosclerosis, which is hardening of the arteries, which everybody gets a little above the time to get to my age, but some people get it early. And the patient's age was 49. Is that right? Or is that the previous patient?

Holly Wyatt:
That was a different one.

Robert Eckel:
Okay. Well, anyway, we don't know the age of the patient. So a stent for an 85-year-old woman or man would not be unusual, independent of their weight. So, I'd like to know how much weight was lost. What was the other reason for the weight reduction in terms of other cardiovascular disease risk factors? What's your LDL cholesterol? That's probably the most important next question for reducing risk for a stent or having a heart attack. So, I think there are too many unanswered questions here to know whether or not the GLP-1 receptor igus would be indicated, but it will, may be needed here. So I think that's something to consider.

Holly Wyatt:
Well, and what I tell people sometimes that come to me with these kind of questions, I did everything I should do. I stopped smoking and I still had a heart attack or, you know, I lost weight and I still had a heart attack is it's modifying risk. It doesn't get rid of risk. It's all about modifying risk. Without the weight loss, you might have had the heart attack five years ago, 10 years ago, or it might have been worse in some way. And so it's hard to know how much impact you've had. It's not just you get rid of cardiovascular disease completely. I think you modify it in some ways. You decrease the risk of it. I think of it more as like an odds game and quality of life and things like that. And I don't want people to think like this person that, oh, I lost the weight and it did nothing. We don't know. I think it did do something.

Robert Eckel:
Right. Just not enough information to make a really intelligent comment. So I'd like to know more, and it may be that the drugs indicated may be that the weight loss was beneficial despite the fact that you needed a stent. Hardening of the arteries occurs over a lifetime. It just doesn't start at whatever age that the stent was placed.

Holly Wyatt:
Got it.

James Hill:
All right, Holly, it's time for your favorite section.

Holly Wyatt:
Okay.

James Hill:
The rapid fire questions.

Holly Wyatt:
Yes. We're going to do rapid fire questions. You get one sentence per answer. You're raising your hand. What would you like to add?

Robert Eckel:
No, I have a question for you two, too.

Holly Wyatt:
Oh, my goodness.

Robert Eckel:
It takes a minute or two for you to address.

James Hill:
Wait, are guests allowed to ask those questions, Holly?

Robert Eckel:
We'll do that at the end. So, Holly, go ahead.

Holly Wyatt:
Okay, save it, save it. Rapid fire. So one sentence per answer. You don't get to really qualify. I know you're going to do that anyway. I'm going to let you do that once, and then it's going to be off. So use it carefully where you want to qualify. So the first one is pretty easy, I think. Is obesity a cardiovascular disease? Yes or no?

Robert Eckel:
No.

Holly Wyatt:
Okay. Two, should every adult with a BMI over 30 and one cardiovascular risk factor be offered a GLP-1?

Robert Eckel:
This is a discussion between the individual and his or her physician.

Holly Wyatt:
There's the qualify. Okay. You used your qualify there.

Holly Wyatt:
Three. Will guidelines catch up to SELECT by the end of 2027?

Robert Eckel:
Yes.

Holly Wyatt:
Okay. Statins or GLP-1s? If you could only keep one for the next decade, which would you keep?

Robert Eckel:
Sure. Statins.

Holly Wyatt:
Ooh, okay. The metabolic syndrome, keep it, retire it, or rebuild it.

Robert Eckel:
Rebuild it.

James Hill:
All right. He was pretty good on that, Holly. He kept his answer short.

Holly Wyatt:
And they were hard ones, right? They required, you wanted to qualify because they're not easy.

Robert Eckel:
Well, I felt like I was going to be scolded.

James Hill:
Now you know how I feel, Bob.

James Hill:
Our last segment, and then we'll let you ask your questions, what we call the vulnerability round. We like to ask you a couple of questions, not about the science, but about the person. And I'll go first, Holly. So, Bob, I keep saying you're in the same boat as me. And the way I put it is we're closer to the end of our career than the beginning. Think about where you are right now. What do you want to accomplish in the next few years personally, professionally? What are you thinking?

Robert Eckel:
Well, Jim, I think that I've always had this belief that the more you learn, the more you realize you don't know. So my goal in this rewired state is still to make a contribution when asked, and have the opportunity to really think further about something I need to know more about. So the passion for learning is still there and hopefully contributing when asked. And if I can further the field of understanding of cardiometabolic medicine. So that would be my goal. I don't want to be out in the left field and just looking at the game on the playing field. I'd like to be more involved, but yet still not return to full-time faculty work. This is a qualifier, but I kind of miss writing grants. I mean, because they stimulate your thinking.

James Hill:
I know. I totally know what you mean.

Robert Eckel:
The creativity we had in science.

James Hill:
It forces you to pull concepts together.

Robert Eckel:
I'll end with this comment. Ed Beerman as a fellow, when I was a fellow at the University of Washington, told me one thing. He told me many things. But one thing he said is one good question deserves three more.

James Hill:
Yeah. Yeah.

Robert Eckel:
So it's this kind of building block kind of scenario.

James Hill:
And the other thing about Bob, he lives in the mountains and he can sit out on his deck and watch the deer and the other animals come by. So that's got to be a little bit of a stress reliever.

Robert Eckel:
Got a great picture of a bear I could show you if you want to see it from two days ago.

James Hill:
All right, Holly.

Holly Wyatt:
One more. And I ask this to a lot of people and I want to see what your answer is. What's the biggest scientific position that you've changed your mind on in your career or something you got wrong and then you later realized?

Robert Eckel:
Yeah, I think I can answer that. There are probably many, but the thing I would come forth with most clearly would be around 2000, I started looking at chairmanships of the Department of Medicine. I thought I wanted to be a department chair.

James Hill:
I remember that.

Robert Eckel:
And as I did that, I looked for a year and a half at three or four different chairmanships that were open. And after my last visit, where I would have taken a job at that last institution, which was not offered, and they said the reason they didn't offer the job to me is that I didn't have enough budgetary management experience. And I said, you know, when everybody came to interview me or when I went there to interview, one of the issues was always related to money, money, money, money, not science and medicine. And that would not have been a job that I ever would have liked. So, my best answer is deciding that becoming a department chair or continuing up the ladder of administrative responsibility is not something I wanted.

James Hill:
Okay. Now, you can ask us a question if it's easy.

Robert Eckel:
Okay. You know, I often, when I give talks about heart disease or diabetes or whatever I talk about, we talk about kind of the interaction of government with healthcare. I mentioned this. I say in the 1950s, 50% of adults smoked in the U.S. In 2025, that's 12.5%. So it's taken us 70 years to go from one in two adults to one in eight adults smoking. And I don't have data for vaping, but young kids are doing a lot of that too. So my conclusion is you don't have to smoke. And it's taken 70 years to reduce it from one out of two to one out of eight. That's an accomplishment. But one out of eight is still too many. But if we look at excess body weight or people living with obesity as a major health problem, not only in the United States, but globally now. I mean, this is an incredible problem. What strategies can we take to modify this major public health problem that is not as easy as tobacco to fix?

Robert Eckel:
You don't have to smoke, but you do have to live. So your thoughts, if you guys have been around, you know, more population science perhaps than I ever will be, but what are your thoughts? What can be done to modify the public health approach to excess body weight?

James Hill:
Well, I'll start, Holly, and then you can jump in because I actually think about this a lot, Bob, is I think what we've learned is that while genetics contribute to weight, the changed environment over time is one that's really pushed weight gain. And the issue is, how do we change that? How do we change the fact that it's so easy to eat poorly and it's so easy to live your life without being physically active? How do we begin to change that? And don't get me wrong, the GLP-1 medications are wonderful, but is our strategy just wait till people are obese and give them the drugs? We've got to go back and somehow affect the environment, but we've got to get people to want to care about that. People will say, oh, yeah, I want to eat healthy and be active. Well, what's keeping you from it? And I don't know. I would love to think the government could play a role there, but I'll have to say that I haven't seen a lot of instances where that's the case. Right now, I don't think we've given people that real, real reason to want to change. Holly?

Holly Wyatt:
I agree with what you said. And this is what I think has yet to see how the GLP-1s are going to help or hurt this. On one hand, I think the GLP-1s are helping people get the weight off with the weight loss. And so that would move us quickly in that direction. We wouldn't have to wait as long as many years. But then the long-term aspect, does it take away then why they want to make a behavioral change like, Bob, you talked about? Now there's no reason to exercise? And then do we not make that a priority with, you know, what our environmental changes and the programs that we put out there? So I don't know. I think the GLP-1s are going to help people lose weight, but I don't know how that's going to translate long-term into the behavioral changes that I think are important. Smoking, a behavioral change, right? And those are a little bit more difficult, and I'm not sure if the GLP-1s are going to help us or hurt us.

James Hill:
But we can't forget prevention. Wonderful treatment mechanisms, but we can't forget prevention.

James Hill:
Okay, to close, I think one of the big takeaways is that obesity and heart disease aren't always separate conversations. So Bob, I want to give you the chance to leave our listeners who may be struggling with obesity, maybe diabetes, maybe heart disease. What's your message to them about where we are and their options for treatment now.

Robert Eckel:
Yeah, let me go to the clinic now, and I'm seeing you because of excess body weight. In my first series of questions relates to your lifestyle. Do you read food labels? How many servings of fruits and vegetables do you eat a day? How many servings of whole grains? Carbohydrate does not cause obesity. Carbohydrate is one of the major macronutrients. How physically active are you? What limitations do you have in physical activity? The only reason, I'm not dodging your question, I begin with a lifestyle assessment initially.

Robert Eckel:
And Holly, you're not old enough or young enough. I'm not sure what the best term is. But, you know, and the fellows that came to the clinic, they got used to Eccles Lifestyle Interview. And so, and then the next time I see them, I go through the same thing. So that's my first thing, always, independent of body weight. And I should make this point. Physical activity is good for you. And a good nutritional package, dietary patterns like DASH and Mediterranean are good for you, no matter what your weight is. Okay, now, once I get past the lifestyle assessment, I ask about smoking and alcohol, of course.

Robert Eckel:
Once I get past there, I want to see what the weight history is. And I commented on that earlier. I need an extensive history of the timetable of your weight gain, your struggle with weight maintenance, et cetera. What's worked, what hasn't. And so when I take that all into consideration, then I'll look at your risk factors for cardiovascular disease. Remember, I'm an endocrinologist, but I didn't state this earlier. My clinic was in the heart center. So I was cross-dressing, if you will, for preventive cardiologists. So in that center, I wanted to get an evaluation of cardiovascular disease risk. Is there a family history of diabetes? Do you have diabetes? What are your lipids, particularly your LDL cholesterol, but also your triglycerides and your HDL? What is ultimately your blood pressure? Is there risk for inflammation? And sometimes I might measure a treatment, a therapeutic, let me rephrase that. I might measure a protein that relates to your inflammation, your level of inflammation. So, all of these things need to be gathered in the way of information before we take the next step. Then the issues about the risk factors, I'll treat the risk factors independent of the weight loss if they're there. But then we'll get to body weight management. And they're considering all of the above. The agents to choose from now are numerous now compared to what they were several decades ago. So, that's kind of my approach to the patient.

James Hill:
Wow. I hope people listening have the opportunity to work with the physician that thinks this way, Holly, that really doesn't just go in and prescribe a medication, but tries to understand the person and match the treatment to the person. Bob, thank you. It's really been a pleasure spending time with you. You have made a difference. I am so pleased to call you a friend and to acknowledge that I think you have made an enormous impact on not just the fields of obesity, but diabetes and cardiovascular disease as well. So thank you for your time.

Holly Wyatt:
Yes, thank you, Bob.

Robert Eckel:
It's been great, guys. I can't tell you how much I miss you. I missed you over the last few years I was there and I continue to miss you.

James Hill:
Right back at you.

Robert Eckel:
So, Jim, when are you going to retire?

James Hill:
Next question.

Holly Wyatt:
No, Jim, you can't qualify.

James Hill:
We're out of time, folks.

Holly Wyatt:
We're out of time.

James Hill:
I'm sorry, but we'll see you next time on Weight Loss And.

Holly Wyatt:
Bye, everybody.

James Hill:
And that's a wrap for today's episode of Weight Loss And. We hope you enjoy diving into the world of weight loss with us.

Holly Wyatt:
If you want to stay connected and continue exploring the “Ands” of weight loss, be sure to follow our podcast on your favorite platform.

James Hill:
We'd also love to hear from you. Share your thoughts, questions, or topic suggestions by reaching out at [weightlossand.com. Your feedback helps us tailor future episodes to your needs.

Holly Wyatt:
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