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Episode 105
Duration 31:57
John Morton

John Morton: The State of Obesity Treatment

Howie and Harlan review the results of a new study testing the effects of anti-obesity medications on cardiovascular health. Then they're joined by Yale's John Morton, a leading bariatric surgeon, to discuss the state of weight-loss surgery and its long-term impact on patients' lives.

Links:

Obesity Drugs

“GLP-1 agonists: Diabetes drugs and weight loss”

“Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes”

“AMA urges insurance coverage parity for emerging obesity treatment options”

“National Coverage Determination: Treatment of Obesity”

“Real-World Adherence and Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists Therapy in Type 2 Diabetes Mellitus Patients in the United States”

“2022 Employer Health Benefits Survey: Section 10 - Plan Funding”

Bariatric Surgery

Mayo Clinic: Bariatric Surgery Overview

John Morton: “Correlating actual one-year weight loss with predicted weight loss by the MBSAQIP: bariatric surgical risk/benefit calculator”

“Outcomes of the Ontario Bariatric Network: a cohort study”

“Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery”

“Weight loss drugs and the push for Medicare coverage”

“Comparative Safety of Sleeve Gastrectomy and Gastric Bypass Up to 5 Years After Surgery in Patients With Severe Obesity”

“A Short History of Bernard Fisher’s Contributions to Randomized Clinical Trials”

“Persistent metabolic adaptation 6 years after The Biggest Loser competition”

“Eligibility for Cardiovascular Risk Reduction Therapy in the U.S. Based on SELECT Trial Criteria: Insights from the National Health and Nutrition Examination Survey”


Learn more about the MBA for Executives program at Yale SOM.

Email Howie and Harlan comments or questions.

Transcript

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University. We’re trying to get closer to the truth about health and healthcare. We’re excited to welcome Dr. John Morton today. But first, we always check in on current news. And Harlan, you promised that you are going to give us an update on the new trial on the anti-obesity medications, anti-diabetes medications. So first maybe just start off and explain to our listeners what GLP-1 receptor agonists are and why we should care.

Harlan Krumholz: Yeah, I think probably almost everyone’s heard about these just because they talk about Ozempic and Wegovy and people from Mounjaro and now Zepbound, which is the new name for tirzepatide, which has been called Mounjaro, that comes out of Lilly that’s just now been approved for the treatment of obesity. These are agonists of a glucagon-like peptide-1, GLP-1. This sounds all, sort of, gotta nerd out on the biochemistry here, but these are basically hormones that have metabolic pathways associated with glucose metabolism and energy homeostasis, and they may be affecting inflammation. The truth is they’ve been around for a while and they’ve been used to treat people with diabetes. They have a modest effect on what—the hemoglobin A1C. That’s the lab test that gives you a net of what your glucose levels have been over the last couple of months. And it’s what people track when they’re trying to control glucose levels and diabetes and so forth.

And over the course of time it was discovered that people who are getting these meds were losing weight. And that wasn’t the original idea. They weren’t really developed with that thought in mind. And now that things have gone bonkers, and we, on the podcast, have talked often about how these meds are changing the face of American medicine, obesity is a big problem in America. So many Americans suffer from it. It’s increasing year on, year out. And finally we have medications that are not only effective in helping people lose weight but seemingly can help reduce their risk.

Howard Forman: So tell us now, what is the accumulating evidence about those real outcomes, not just obesity and not just diabetes—as though that’s not enough—but what are we learning?

Harlan Krumholz: Well, just to review again, we had a wide range of drugs to treat diabetes and there began to be some concern that even though they were successful at lowering glucose levels, they might’ve been increasing cardiovascular risk, paradoxically. And so the FDA came in and said, if there are any new diabetes drugs, you have to do what they called cardiovascular outcomes trials. You had to do clinical trials to ensure the safety of these drugs. Now you can imagine how hard that was to enroll people because you’re enrolling people to show safety, not benefit. But they were able to do these large trials to show that at least these were safe.

And in fact, these drugs, like the GLP-1 agonist, actually reduced risk, and that was out of proportion to the benefit that they had on blood glucose. And so for a while we’ve known that these drugs, when used in people with diabetes, they could reduce risk. And then a lot of people with obesity and diabetes end up being treated and they also had this risk reduction. But the question was, what if you started treating people with obesity who didn’t have diabetes? It was this really in effect that was singularly about benefit in those who have diabetes.

Howard Forman: Now we have the drum roll. Please tell me what we learned.

Harlan Krumholz: This trial, which was done by Novo Nordisk, the maker of semaglutide, which is the drug that’s in Ozempic and Wegovy, enrolled thousands and thousands of people in a study and randomized them. These are people with obesity and existing... they’re high-risk people and existing cardiovascular disease. And they said, what if we treat the obesity? What’s it do for cardiovascular risk? We’ve known this for a while, by the way, because of the SEC announcement, but the trial itself added in a lot more information. There was a 20% reduction in risk, and this was over about three years of treatment.

The absolute difference between the groups made it so that you had to treat about 67 people to avert one event, but that’s not bad in the scale of things. When you look at it, the 20% reduction is similar to what you would see with something like statins. And what was notable, Howie, was that these were very well-treated people, meaning that they had heart disease and they were on statins, their blood pressure was good, their LDL, the bad cholesterol was low. I mean, this was a group who was about as low a risk as you can make them with conventional medications. And we still got a 20% on top of really good preventive care. So lots of people were excited about this.

Howard Forman: Now, one of the things that was in the trial, which surprised me at least a little bit, is that the weight loss seen in this group was less than we’ve seen in the previous trials. Has there been any discussion about why that’s the case? Is there something different in this population?

Harlan Krumholz: Well, I think that we haven’t had any head-to-heads yet between the different types. And the trials do have differences in population, maybe this population is a little bit older than some of the other populations, maybe the levels of obesity. Interestingly, they had people from BMI of 27...

Howard Forman: Yep.

Harlan Krumholz: ... To 30, so they even had people with a BMI under 30. Now the definition of obesity really starts at a BMI of 30, so they’re going a little bit lower. And they’re saying if we treat people in that early stage, does that make a difference? I’m not sure exactly why, but there still was almost I think a 10% reduction in weight. People did lose weight. And one of the interesting things, by the way, Howie, about this was, one of the questions might be how about people who are just over the borderline that the lower end of the BMIs in this trial, did they get experience as much benefit as the other?

Howard Forman: I think they had more, right? Isn’t that the case?

Harlan Krumholz: If anything, they had more, right?

Howard Forman: Yeah, I was shocked.

Harlan Krumholz: So probably there’s not a lot of difference among the groups, but they definitely didn’t have less. And so it suggested, maybe treating those who are just barely into the obesity category was beneficial. We should be treating early, not waiting until people are—

Howard Forman: Yeah, and that’s one of the questions that I’m going to be asking Dr. Morton when we talk to him today is, when do we treat obesity? Do we wait until it gets really bad or do we treat it a little bit earlier? And this trial would suggest earlier is certainly not worse. It is interesting that this week, timed to this trial’s release, the AMA comes out with a statement saying that they now advocate for insurance to cover obesity medications on an evidence basis. I don’t remember the exact words, but basically using an evidence-based approach. And my question for you is based on what limited information we have and from big trials—what would you say the recommendations are right now? For what categories do we have strong enough evidence to say we should be treating if the patient wants it?

Harlan Krumholz: Well, look, I think we need to move from this idea that this is about a cosmetic approach, that this really represents an improvement of health and health promotion. And look, we’ve got long-term evidence about the safety of the drug because it’s been used in people with diabetes for a long time. The effectiveness in treating obesity is really clear. And now we have evidence, not only does it do things like lower blood pressure and improve lipids and slow the progression to diabetes among those who don’t yet have diabetes or even reverse diabetes and people who do—we have actual evidence in high-risk individuals that it reduces the number of heart attacks and cardiovascular deaths and so forth so that it’s reducing risk. I think we need to start thinking about these like we do statins, and it’s one of the strongest evidence bases there are for preventive medications. As you know, CMS doesn’t cover this right now—

Howard Forman: I know.

Harlan Krumholz: ...because they don’t cover weight loss drugs.

Howard Forman: And most of the insurance companies aren’t covering it because employers get to make those decisions for the most part or whatever plan you buy can or does not have to include it because it’s not an Obamacare-required condition.

Harlan Krumholz: Yeah, I mean, one of the things is in healthcare we spend a lot of money on things that we don’t have good evidence about, we’re not sure about, and we allow that. And then there are things now that come up like this where, yeah, I mean, I think that the evidence is quite strong that it’s quite beneficial. Now you need to know some people take this, can’t tolerate it, and it was about 8% of people... 16% discontinued because of side effects in the treatment group, but 8% discontinued in the placebo group.

Howard Forman: Right.

Harlan Krumholz: So you have to subtract that, but you get like one in 12 we’re unable to continue for... this was 40 months, a pretty long trial, but most people did tolerate it and experienced the benefit and I just don’t think the costs should be a reason that people can’t take it.

Howard Forman: And I’ll add just one more thing. I think as a society we just need to come to some decisions about how and what we pay for, what is the standard for paying for these things. What you just said also about discontinuation turns out within the clinical trials, the numbers are consistently, like you described, very low in the real world. When people start up semaglutide, they quit 50 to 65% of the time within, I think, a year, a year and a half. So that’s a disconnect between it. A lot of people think it’s because when you’re in a trial, you’re not having to pay anything for it. You’re involved in monitoring, you may feel shame if you discontinue it. So we’ve got to also figure out how do we take care of all those people that aren’t really going to continue taking it for one reason or another and make it accessible to as many people as possible.

Harlan Krumholz: We’re trying to launch some studies working with Ania Jastreboff, and we’re trying to launch some studies of real-world experience with this, trying to understand how do you optimize this treatment, how do you get the best?

Howard Forman: We’re going to keep coming back to this, that’s for sure.

Harlan Krumholz: So let’s get onto our guest.

Howard Forman: Dr. John Morton is a professor of bariatric and minimally invasive surgery at Yale. He serves as Vice Chair for quality and is the system lead for surgical quality and bariatric services in the Yale New Haven Health System. Before coming to Yale, he held similar leadership positions at Stanford Medical School. Dr. Morton is board certified in surgery as well as obesity medicine. He has written numerous book chapters, articles, and research papers and is an editorial board member of many renowned health- and obesity-related publications.

In addition to being honored for his teaching and scholarship, he’s continued to fill roles of leadership at the national level. He obtained his bachelor’s, master’s, and medical degree from Tulane University and he received a master’s in health administration from the University of Washington, where he was a Robert Wood Johnson Clinical Scholar. And we have been actively and excited about talking to you for many months because one of the themes of this podcast has been obesity, obesity treatment, obesity as a disease, and so on. And you are an obesity surgeon, and you have basically been an active surgeon from the beginning of the obesity surgery revolution to now. But what I want, if you could to start off with, is just to give our listeners a sense about the types of surgeries that have been done and what is the current state of the art.

John Morton: Well, thank you to you both for having me today. I’ve really enjoyed getting to learn more about the podcast, and it’s an honor and privilege to be with you guys today. So bariatric surgery and its modern iteration started roughly about 20 years ago. What sparked it is really the fact that we were able to do it laparoscopically with small incisions. I’ll never forget as a young surgery resident reading a book that said laparoscopy will take over all of general surgery—the only exception will be obesity. I remember reading that, and of course, that’s where the sweet spot was because in the old days when they did these procedures, just the incision alone was quite morbid, 50% hernia rates and infection rates. But since then we do it laparoscopically. There is now an accreditation model for all the bariatric surgery, over 900 accredited centers and, more importantly, we teach people how to do these procedures.

There’s roughly about three main procedures. By far, the most common currently is something called the laparoscopic sleeve gastrectomy that’s followed by the Roux-en-Y gastric bypass. And lastly, the duodenal switch. There’s different variations with each of them, but I can briefly describe the three if you’d like.

Howard Forman: Yeah, please.

John Morton: Well, we’ll start first with the sleeve because that’s the easiest one to conceptualize. What we do is we take the stomach that’s roughly about the size of a football and make it into a long skinny tube, roughly about the size of a banana. And that accomplishes a few goals. One is, it is restrictive, but a big change in the last 20 years is in understanding the bariatric surgery is not just restriction, it’s actually metabolic changes, physiologic changes. So with that resection of the stomach, we remove the seed of hunger, the fundus where you have ghrelin being made.

The other interesting thing is that you get food going through that sleeve quickly and it reaches the distal intestine fast. And what that does is it turns on GLP-1 that’s been in the news. We were a GLP-1 agonist before GLP-1 was cool. So in bariatric surgery, we’ve also raised GLP-1, but there’s a lot of other things that happen. Energy expenditure goes up. Some of the other hormones like PYY are altered in favor of losing weight. So a lot of those things happen. Now with the bypass, it is a little bit different. It’s an older operation and that operation has been around since probably about almost 60 years now. And what we do with the bypass is we make a small stomach roughly about the size of an egg, divide the intestine in half, bring one half up to the small stomach and then reconnect it. It too can provide excellent weight loss, but it is really very effective for diabetes and extremely effective for acid reflux.

The last procedure is a duodenal switch. Duodenal switch is a much, much rarer procedure, probably on the order of, maybe, less than 1% nationwide. And what it entails is bypassing the majority of the small intestine, only about 300 centimeters are left for absorption of nutrients. So that is a higher-risk, higher-reward type of procedure, and we really confine it for patients with advanced stage of disease, which has been another big advance for us in bariatric surgery. We really looked to tailor therapy to stage of disease, and obesity is a disease as declared by the AMA about 10 years ago. So those are the three main ones.

Howard Forman: Can you speak a little bit to two points that are related? One is, what are the obstacles to doing randomized trials between the different types of surgeries that are being done? I know there have been some small trials, but a bigger one, and secondly, about two thirds of people that go on GLP-1s, maybe a little less, don’t last more than a year. With surgery, you obviously can’t give up on the surgery once you’ve had it—you’ve had it—but I’m just curious what percent of patients at a year are satisfied with how their surgery has worked out?

John Morton: Yeah, we’ve got a lot of data about that. The overwhelming majority are happy with their surgery. In fact, the most common comment I get from patients is “Why didn’t I do this sooner?” So we’re talking in excess of 90% for that. So it’s one of the things that are—I like to say it’s a happy specialty. I mean, that’s one of the reasons I enjoy it, is that I have a lot of happy patients. I also don’t have a very high complication rate at all. Our nationwide mortality rate’s about one out of a thousand, which is comparable to hip or knee replacement. My personal experience, and I’m always a little reluctant to bring up, but I’ve done about 6,000 cases without mortality. That’s what I want to do until I retire. So it can be pretty safe and it’s definitely effective and most people are very much happy with it at one year.

Now, if we take it out a little bit further, 3, 5, 10 years, the patients who aren’t as happy are the ones who’ve regained their weight and that frankly is an Achilles’ heel for bariatric surgery. We have excellent one-year data, and with some trials, we’ve been able to follow it out even 20 years. Mostly population-based stuff out of Sweden and Canada. But one thing that would enhance our field a lot is better ability to track patients.

And I think this is where telehealth in the broadest sense would help us out. Things like remote monitoring. I’ve lobbied the insurance companies for coverage over the years and I have good relationships with them, but one of the things I’ve always advocated for them is that they need to get smart scales for these patients. The act of weighing yourself is actually a trait associated with keeping your weight down. We used to think that weighing yourself a lot would actually be detrimental to the wellbeing of a patient, but it’s opposite. It actually helps keep you on track. We do provide glucometers for diabetics. Why aren’t we giving scales to some of these bariatric surgery patients? The last point about that is it’s easier to treat 10 to 15 pounds of weight gain than it is a hundred. So a stitch in time will save nine; an ounce of prevention’s worth a pound of cure. So if we know about it sooner rather than later, we can help.

Harlan Krumholz: One of the issues that’s come up with the GLP-1 receptor agonist is the concerns about equity and who’s going to get them, and especially with the cost. Are you facing any of that in surgery? I mean, who’s actually getting the bariatric surgery and are we really reaching all the populations who might benefit from it?

John Morton: It’s a great question, and initially, most of the people that were getting bariatric surgery were well insured and white, but that has changed over the last few years. One of the big impediments was frankly coverage. I became president of my society I think in no small part because I advocated for coverage and got coverage for a lot of our surgeons. And one of the places that we lacked coverage nationwide was Medicaid. About, I guess, 10, 15 years ago, only about half of the country had coverage with Medicaid. Now proud to say 49 of 50 states have coverage, Montana being the only exception, and for a while it was because they didn’t have a bariatric surgeon, but we’re getting better coverage. And there was a recent article, and I did the commentary on it. We’ve actually seen an uptake in doing more and more of these cases with underrepresented minorities.

So it is getting better. I think in many ways what’s going on with GLP-1s now is what happened with us 20 years ago in bariatric surgery. Mark Twain said, history doesn’t repeat itself, but it sure does rhyme. And that I think is what we’re seeing. What happened about 20 years ago for us, many of the procedures we were doing were cash. They were not covered by insurance. You’re seeing a lot of that happening right now with the GLP-1s. You’re also seeing some backlash, which has happened with bariatric surgery as well. Everybody wants to pull on Superman’s cape. When you see something wildly successful, inevitably there will be some sort of backlash, but I think in terms of equity, what will make it more equal is coverage. And the biggest impediment right now to coverage for the GLP-1s is this mandate, and CMS saying they won’t cover any obesity medication at all, and it’s a blanket refusal to coverage and it’s an out-and-out discriminatory practice, frankly.

This is something, that why is this disease singled out amongst others? I hear it’s too prevalent. 40% of this country’s obese or overweight. Well, how many of this country is pre-diabetic or diabetic? There’s no hesitation to cover them. So I think we have to get over the stigma for one reason so we can improve the health and welfare of our population because there’s a lot of downstream complications of carrying weight, cancer, COVID, cardiac disease, and we’re paying for it already. We’re paying for all the complications. Why not pay for it upfront so we can prevent some of these problems later?

Howard Forman: You mentioned early on the distinction between the three different types of dominant surgeries and that the sleeve gastrectomy is the dominant one, but it also has a lower likelihood of reducing or lower loss of weight compared with the Roux-en-Y, which is a much more complicated surgery. Can you explain why that has become so dominant given that it may be less effective? Does it have anything to do with adverse events or outcomes otherwise?

John Morton: It’s a great question, and I think it’s coming from both sides, both from the surgeon and from the patient. So from a patient standpoint, over the last 20 years, one thing I’ve learned from patients is they want less invasive, not more invasive. They want simpler, not more complicated. So patients will come in first of all asking for the sleeve. Now there’s some strong, in my opinion, contraindications for doing a sleeve if you have pathologic reflux where the lining of your esophagus gets burned because of the reflux or if you have very advanced diabetes. So in that case, I will recommend the bypass. Now, patients will sometimes push back, but I will do my best to educate and if at the end of the day, they still want the sleeve, I will provide it as long as there’s no harm involved in it. Main reason being is that a therapy is better than no therapy at all, and there’s a clear and present danger to doing nothing for these patients because it’ll end up getting worse.

The other side of the coin is why are surgeons doing it more? Frankly, it’s a more straightforward procedure. It takes, I did three yesterday, it takes me about 40 minutes to do the procedure. It’s a very quick procedure. Patients are in the hospital for a day or two. I think there is certainly some advantage in being able, the simplicity of it. As far as adverse events, really, once you get past the first week, it’s pretty rare to have problems with the sleeve. The only exception can be reflux, and it’s a very pathologic reflux. It happens in, maybe, 5% to 15% of patients, and in those patients, the traditional PPIs and the anti-acid medications do not work, so then they will require conversion to a bypass.

One thing that we’re doing at Yale is trying to figure out why. And one of the things that we do is we scope our patients prior to surgery, and one thing we’ve learned is that the people who are at most risk having reflux after surgery are the ones who have reflux before surgery. So it’s simple that way, and when you do it that way, you don’t have that degree of reflux afterwards. But my hope and belief is that we can take the sleeve, which is common, safe, straightforward to do, and augment the results, augment the results with the GLP-1s. I harken back to, I’m trying to remember the surgeon’s name, Bernie Fisher from University of Pittsburgh who did the famous trials of the lumpectomy versus mastectomy, lumpectomy plus adjuvant therapy. And as you guys know, the mastectomy was a mainstay for breast cancer in the ’70s—

Howard Forman: Decades.

John Morton: ... in the ’80s, and it was very disfiguring, and he figured out if you augment the lumpectomy with neoadjuvant and adjuvant therapy, you can get equivalent results.

The other big insight he had was that the disease is not local, it’s systemic. Another insight for us in bariatric surgery. So that’s why I’m of a firm belief that if we use these drugs before and after surgery, we’re going to need to get equivalent results with the sleeve and the bypass. Again, it calls for study to figure out if that’s actually the case. Last point is about the bypass. There can be some complications later. The big ones are ulcers, but also bowel obstructions and they can occur at any time. I think you guys may be aware of Lisa Marie Presley’s demise, and it was from a bowel obstruction. Now, her particular procedure was a duodenal switch. It was not a gastric bypass, but what she died of was the fact there was a small bowel obstruction that went unrecognized and unfortunately she was on opiates, which can sometimes mask the pain associated with the bowel obstruction. But again, that can happen at any time and that’s something that simply doesn’t happen with the sleeve.

Howard Forman: Last question from me, at least, Harlan has taught me to use the term “Class III obesity” as opposed to “morbid obesity.” But in the early years of obesity surgery, we were only doing these surgeries on the most obese individuals.

Harlan Krumholz: Those with the most severe levels of obesity.

Howard Forman: Right, right. With the highest BMIs, more than 35 or 40 in many cases. Is your recommendation now, if somebody is already a BMI of 30 or 35, is it better for those people to be treated earlier, later? Is it irrelevant, then you really just have to look at the whole picture. What is the recommendation now?

John Morton: I always think it’s better to treat early-stage disease and late-stage disease. There’s no question about that. Our indications are BMI over 40 or BMI over 35 with a medical problem. It was that way for the last 30 years. About a year ago, we created new guidelines based on evidence and the guidelines now advocate for a BMI 30 to 35 if you’re diabetic. And we know diabetes is such a pernicious disease with complications that it makes sense to intervene sooner rather than later with some of those patients. And I do think the highest risk of recurrence is with higher BMIs, the best results are with lower BMIs. So it’s a no-brainer, the patient should come in sooner rather than later.

And now with the new drugs, I think it’s a great thing that they’re able to have alternative therapies if the drugs don’t work or they can’t tolerate them, and there is a subset of those, there’s always bariatric surgery in your corner. It’s similar to what we’ve seen with heart surgery and the high standard that we have in cardiology now. And certainly there’ve been other examples, but I think they’re complementary. They’re all in the same continuum. And as a bariatric surgeon, I welcome the GLP-1s because I care about my patients and if you have therapy that works, you’re going to be happy for that. And we treat about 1% of the affected population. There’s a lot of folks out there that need help.

Harlan Krumholz: Well, I want to thank you. I want to say you guys were really out in front on this idea that this isn’t about losing weight, but it’s about health. It’s not about lack of willpower or failure when people get surgery, it’s about treating their condition, in the same way it would be treating their diabetes or their hypertension if they’ve got advanced disease. You guys were way out in front of that framing, I think, in terms of thinking about this. And then, of course, I think on the medicine side now, there’s still a lot of education needs to take place because there’s still a lot of stigma, bias, and even suggesting that “why can’t you just do it on your own?”

And the truth is, for many people, the way they’re wired, the kind of environment they live in, they’re just not going to get there. And that’s not a failure. They need to try other strategies. And I just want to give credit to you guys and the surgeons in particular. I think you guys were way out in front on this in terms of thinking that they required an intervention and that wasn’t a failure, that’s a treatment. And anyway, I wanted to salute you for that, because I think, and thinking about a pluripotent way, the nutrition, the activity, you weren’t just “go, let’s just do the procedure,” but you had a whole behavioral modification.

John Morton: No, we did have a comprehensive approach, and it was based on experience because in the ’80s and ‘90s, that’s what they used to do, Harlan, they would just operate and then they wonder why things didn’t work. I think the one study that really exemplified how much of this is physiology, not psychology, is the “Biggest Loser” study by Kevin Hall. If you ever saw the show, people really wanted to lose weight. You have to be very motivated to get up on national TV and be humiliated. Because that’s what the show was about. Every single one of those patients regained their weight. And it wasn’t because they lacked motivation; it was because they could not overcome their physiology.

And he looked at the hunger hormone, the satiety hormones; they were permanently altered by the dieting. They went up to higher levels for hunger, lower levels for satiety, and that happens each time you diet. And so they have to overcome that. There was only one patient following the “Biggest Loser” study that lost weight, and that was someone who had bariatric surgery. So this is obviously pre-GLP-1 era, but it just goes to show you, and I’m glad you brought up the point, it’s about physiology, not psychology.

Howard Forman: We really appreciate you joining us today and really appreciate the work that you’ve done in this field.

Harlan Krumholz: Yeah. And John, thanks so much and it feels so fortunate that you’re here with us at Yale, so thanks for joining us too.

John Morton: Thank you, guys. Really appreciate it.

Harlan Krumholz: Well, that was a great interview. I’m so glad we had John Morton on today.

Howard Forman: Yeah. And it was fun for us to frontload the episode talking about the new semaglutide trial and the challenges of GLP-1s, and then to really dive in deep with somebody who’s an expert on the surgical treatment of obesity and the holistic treatment of obesity. So I appreciate that we were able to do that all together.

Harlan Krumholz: Yeah, we reorganized again today. So everyone, you’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.

Howard Forman: So how’d we do? To give us your feedback, keep the conversation going, you can email us at health.veritas@yale.edu or continue to find us on Twitter.

Harlan Krumholz: At H-M-K-Y-A-L-E. That’s @hmkyale.

Howard Forman: And I’m @TheHowie, that’s at T-H-E-H-O-W-I-E. Again, you can email us. You can also reach out to us where I am the faculty director of the healthcare track and founder of the MBA for Executives program at the Yale School of Management. Feel free to reach out via the email or look at our website at som.yale.edu/emba.

Harlan Krumholz: Health & Veritas is produced with the Yale School of Management and the Yale School of Public Health. Thanks to our researchers, Ines Gilles and Sophia Stumpf, and to our producer, Miranda Shafer. Outstanding week in, week out. Talk to you soon, Howie.

Howard Forman: Thanks very much, Harlan. Talk to you soon.