GLP1_Butsch Interview-enhanced-90p

So, hi all you BTK fans. It's Scott here along with Jason and we're super pleased to kind of touch on the topic we have not addressed and that's the anti obesity medications and some of the hot topics that are around there and I'm super pleased to have Dr. Scott Bush who is here from the Cleveland Clinic to join us who is heading our Bariatric and Metabolic Institute pathway.

Scott, thanks for joining us so much. Thanks Scott and, uh, I appreciate the time So for all of our listeners out there, can you give us a little bit about your background about how you got into this space and what is it currently that you do right now? Yeah. So I, I practice obesity medicine, which is a growing subspecialty of internal medicine.

I did a fellowship in this field in, in obesity medicine about 17 years ago. Uh, at the time there were no fellowship. So I ended up being the first one in the country to do so. Now there's, 25 subspecialty fellowships across the country specializing

in, you know, obesity medicine. And mainly I focus my practice on taking care of people who have obesity specifically who obviously need to lose weight and.

I've obviously done this for a long time. So if you could just kind of set the stage for us from a historical standpoint so we, you know, there's a long history of of bariatric surgery and its efficacy and within the last five or six years, there's been a lot of new tools in the toolkit for, you know, the medical treatment of obesity.

You know, I'm old enough to where I remember, you know, kind of the craze in the eighties and nineties of Fen Phen, but maybe you could talk about, you know, kind of the, the history of obesity medicine of anti obesity medications, and how now is different? Yeah, very good question, and I think, to set the stage, I think we have to realize that it's been stained with bias.

The thought is for the most part, all of our treatments, the way we've treated patients with obesity, has largely been with the thought and the belief,

unfortunately, that obesity is a behavioral problem. So the focus, primarily, has been throughout the ages, through modern day treatments, is to change the behavior in the person who has obesity.

And if they can't cut it, if they don't have good behaviors, The thought was maybe we can give them a medication, or maybe we can, you know, in the 60s, do a surgical procedure. But all that really focused on reducing caloric intake. So the thought was that people who have obesity are always hungry. These are all stereotypes.

Always hungry, uh, don't have good behaviors, don't have enough willpower, don't exercise enough. And the thought was if they can't do those changes, or if they're not losing weight, then they're not changing their behavior, and thus You know, their failures and so not only that implications on the person, the individual themselves, but it really had implications on our healthcare system and the way we, we got at this disease, obviously it wasn't thought of as a disease.

So therefore giving

thyroid, giving amphetamines giving, uh, you know, the fen fen beginnings all had to do with let's suppress the appetite in the person who has obesity. Even bariatric surgery is, as you may know, started with the thought that we have to give someone a smaller stomach. If they can't change their behavior, let's give them a stomach that's smaller, so they eat less food.

And let's make sure that they have a malabsorptive procedure, so even if they eat a lot of food, they're not going to absorb all those calories. And thus set the stage for obesity treatments in the 1960s, 70s, 80s, 90s. And so FENFET actually that you mentioned was interesting because it was the first medication that actually was a dual, you know, two prescriptions of two different medications that actually was quite effective.

There were people lost maybe 10, 15 percent of their body weight, which was really remarkable. Um, but the thought again, these were short term treatment options. This was, go on the medication, change your behavior, and when you change your behavior, go off the medication, and you should

be fine. Um, but the remarkable, around the history of bariatric surgery came the understanding like everything in, in medicine.

We first start with surgeons who are innovative and they do things and they figure things out because they ask themselves questions. They do the operation, it changes the physiology, let's say, and then science and medicine catches up and drug targets go to those areas of the body that So, obesity, in the end, is a disease, is a dysfunction of our body's ability to regulate weight.

And therefore, we have to come up with treatments that target the areas that control our body weight. Scott, I want to jump in there. Before we go into the medications, let's take it one step higher and talk a little bit about obesity in general. Like, as you said, in the past, it was always just like, ah, they eat too much, they have a sedentary lifestyle, it's all their fault, anything like that.

Can you give us a little background to obesity? Maybe some stats, like where are we at and where have we come? I mean, is it, is it still increasing? And we see those,

sometimes those maps of the U S that over time, the color graphs, they go from like one color to another color, the way it's like an epidemic proportion.

But before we go into the conversation, set the canvas for us, tell us a little bit about obesity in general. What is the definition of obesity? What is super obese and what is the trends that we're seeing today? A lot of questions baked into that, uh, big picture question. I mean, First of all, statistic wise, I mean, this is, this is, uh, a disease that is not quieting.

It continues to affect, uh, adults. We see over 40%, 42 percent of the United States has obesity. That's defined currently by those statistics, looking at a BMI over 30. We have childhood obesity, 19% of children have obesity. We see that the people who have overweight and obesity. Which is a BMI over 25 that affects nearly three quarters of the population.

And it's predicted that half the population in the

United States in five years will have obesity. So it's, it's not stopping all the things that we've tried to do changing the walkways of our streets, changing the food. All of this kind of stuff has unfortunately now worked. And it's, this is a global pandemic.

This isn't really specifically to the United States. There's people who have genetic, uh, forms of obesity we see that 13 to 15 types of genetic and syndromic obesity. So people are born with, uh, the focus of their mutation is in the regulatory pathways and they develop obesity. So, so if we think about that of, of this, of this growing pandemic, we've largely missed the opportunity to treat this disease.

And that's why we're seeing. So, this is a surgery podcast, and I would be amiss not to just ask one question. I know we're going to

spend the majority of time on the medical side of the house as well as maybe some thoughts about what are medications after surgery. But Jay, can you kind of just pick the landscape of the current surgeries that are for for obesity and, and you know, for diabetes?

Just kind of give our listeners out there just a brief overview on that. And then we're going to dig heavy into the medical side. Uh, sure. Yeah. So in the United States, there are four ASMBS, American Society of Metabolic and Bariatric Surgery. Endorsed procedures, those, you know, being the, the, uh, lap band, which is, is still to, to a much lesser degree than in the past, but is actually still an endorsed procedure and performed in the United States.

The sleeve gastrectomy, the Roux en Y gastric bypass, and then a few variations of the biliobankeratic diversion and duodenal switch with most recently the, you know, single anastomosis procedures, the SADI procedure gaining popularity. You know, we've as Scott mentioned, there's, uh, a long history dating back to the 50s and 60s and, you know, these are effective,

uh, treatments for both the control of obesity as well as the, as well as the obesity related comorbidities.

It's very, I think, as I mentioned, I think it's very exciting to have kind of new things in the toolkits and, um, as you mentioned, You know, we started the surgeries first and we're still trying to understand the, the physiologic implications and the effect on some of the gastrointestinal hormones and really the metabolic effects of surgery that now we have to, to target.

So with that, you know, could you tell us, you know, what are the different classes? I know there's a lot of different things kind of in the, in your armamentarium when it comes to medical treatment of obesity. What are some of the different classes of the medications, um, just as a starting point? And then we'll get into how do we apply those in our treatment algorithm along with surgery?

Yeah, really quick just to, uh, to piggyback on what you were just saying. You know, it's, it's really important to understand that bariatric and metabolic surgery changes the physiology, changes not only

gup hormones, as you were just saying, in the opposite direction they would go if you just went on a diet and lost weight.

They, they change bile acids, they change the microbiome, the bacteria in our gut, they change the whole system so the body then adapts itself and begins to regulate to a smaller fat cell. And therefore, you see the whole weight range decrease and stabilize after surgery, uh, which is quite interesting and that's obviously a whole nother conversation, but I just want to add that one piece.

Um, In terms of medications, we've, again, largely thought of these medications as just appetite suppressants. And so it's been basically one class. But if you think about the different types of medications and where they work, let me just sort of bifurcate it and say there's drugs that work in the brain, and there's drugs that work in the gut.

So the drugs primarily have focused in the brain, specifically the hypothalamus, an area of the brain. That regulates our body fat and have largely tried to hit

targets that decrease food intake and increase our metabolism. These are located in the hypothalamus. So you have, uh, numerous drugs have worked in that way.

Over the last decade you've had sort of these second generation drugs. First generation drugs being sort of these stimulants, these amphetamine based drugs. Uh, a medication called Fetramine, which is amphetamine like, is still part of that Fen Phen, is still probably the most commonly prescribed drug.

And then over the last decade, you've basically had these second generation drugs that, again, have targeted the areas of the brain within the hypothalamus. But one of the drugs, which, again, has been around for 20 years, about 19 years ago, I first started using these glucagon like protein 1 receptor agonists.

So these are These are drug, this is a drug that mimicked a hormone that is naturally produced in the body and is responsive to, uh, sensing sugar in the, in the gut and having nutrients go

through the digestive tract. And from that, we've seen not only these GLP 1 receptor agonists in 2005 when they came out, but again in 2008 and 2014.

But now you see just this, uh, this incredible boom in, in the efficacy of the drugs. And again, specifically looking at this one gut hormone, GLP 1, but also what we see in the future, which I'm sure we'll talk about is sort of what's to come. And again, really this focusing the drugs in the gut that are working on the digestive tract.

That has signaling to that very area of the brain that the other drugs work in. It just so happens that these drugs have, you know, more effective, highly effective drugs and have more implications than other drugs. And other organs of, of the system. Scott, it was amazing what you just said there that these drugs have been around for decades.

And so I guess my, my first question is why now? I mean, if they've had around for

decades, why does it seem like in my local community, I can't tell you the number of people who aren't even obese are taking a little bit of this medication or that medication just kind of got a little nip and tuck here, if you will.

I hear it all the time. So. What has changed, if anything? Yeah, it's a, and I, and I, that question specifically, what you just asked is a, is a good thing to pick apart in, in saying that if you think about obesity as a disease, first of all, it's, if you're a healthcare system, uh, you run a healthcare system or you run an insurance company, it's, why would I want to spend any money and help these people who just need to help themselves?

So again, you know, putting in some bias to frame this, this question that you just asked. Secondly, the thought is, well, if these medications are around, you know, first of all, they're not needed because the person just needs to eat better. So there's not really an understanding or interest in using the medications.

Um, but they're available

in, because they have an effect on diabetes as well. So they basically first came out as diabetes medications, but all of us, you know, who read the literature knew that these. Medications also were very effective in changing body weight. So, what you see now is people who have been used to using these drugs for diabetes.

All of a sudden, yet, you know, start to read the papers and in the last three years, they're like, wait a second, not only are these medications used for diabetes, they also have a huge impact on body weight. Well, now I can help my patients even more. And so you see a large, uh, awareness in the, in the provider, in the clinician population that now has been used to using these medications in part to treat diabetes, who sees now that I can help my patients who have obesity.

And so I think that there's where you're seeing sort of this interest of, of using the medication that said to your second part of your question,

there's people probably who do not have obesity who are on these medications. And that's largely because unfortunately you have a rebranding of the cosmetic industry that's been sort of baked into let's help a health and wellness and have built an enterprise 10 trillion or excuse me, 10 billion businesses.

That has been established now are scared because now you have drugs that actually help body weight. And you don't have to go out and do your Dr. Oz, you know, supplement that is supposedly do something which does nothing, which we know. So you're seeing evidence based therapies actually trumping, uh, non evidence based therapies that have existed for the last two decades.

So let's start with Phenermine. So what I see a lot is, um, there's still a lot of, of bias in, within the medical community about patients going on Phenermine because there's, I think people still have that. You mentioned it's similar to Fen Phen, people still have that kind of Fen Phen memory of abuse

potential as well as the safety side, uh, safety profile, it's effect on the heart.

So, I even have primary care doctors, you know, kind of losing their mind when they find out that we're putting patients on, on Phenermine. So can you kind of, number one, dispel that and then talk about the effectiveness or the efficacy of Phenermine? Then how you mentioned pH phentermine and then the GLP one agonist, but how do things like contra, emia, you know, how do you treat those medications and how do you stepwise, you know, kind of take patients through this journey of these various medication classes?

Yeah, I, and I like your question because it gets to the core of the bias that existed. So here it was phentermine, it is not an amphetamine. There's no evidence that it's addictive. Um. The thought was that this medication has existed since, like, 1959. It was put in, co prescribed with fenfluramine, which is the one that caused heart problems, increased alveolopathy, heart failure.

Um, that increased serotonin in the brain, but they didn't know serotonin receptors were in the

heart. And so, then fluoramine was taken off the market, but fentramine has existed because it's a perfectly fine medication. So couple things to dispel. One is the misconception that it's dangerous. It's not.

But think about it this, this way. If you think obesity is a problem of overeating, and you give somebody a drug, fentramine, to help them reduce their intake. Which is the sort of the monovision that most people have, and then they don't lose enough weight. So what do you do? You want to increase that dose.

So largely people have jacked up the dose of phentermine. In some people who just can't tolerate stimulants, you know, there's people who just don't like to drink coffee because it makes their heart race. All of a sudden you have a population that is sensitive to these stimulants. And then as an observer, when you don't think that obesity is a disease, you're like, see, why would I ever want to put you on this medication?

You just need to change your behavior. So that has been baked into our

system, Jason. And so when you have that in mind and hundreds of thousands of providers have thought that way, then they've not thought any other way that we should treat obesity in a different way. So the thought was. If it's Contrave, go on Contrave, and when you lose weight, go off Contrave.

But what do we do in every other disease? If the, if the drug works, we keep them on the drug. If it's a blood pressure medication, chemotherapy anti cholesterol medications, we don't take people off the medication, we keep them on, because we know it's a chronic disease. But if you don't have a, an idea or you, or a disbeliever that it's a disease, why would you ever keep these medications on?

So that, that sort of frames the picture. When you get into drugs like Hantrave, which is a combination of naltrexone and bupropion. Uh, if you get into something called Qsimia, which is fentramine plus topiramate, topiramate is a, a migraine medication that's been around for decades. If you talk about oralistat, or maybe not as good example would be oralistat, but

these drugs were, again, thinking that the brain, and which obesity is a disease of the brain, It's targeting the brain.

Oralistat, unfortunately, was still in the sort of the old mind of thinking it's just about reducing fat intake. So Oralistat reduces the, our consumption, or we don't absorb about 30 percent of our ingested fat when we're on this Oralistat. Just like the gastric band that you mentioned before is the thought that all I need to do is put a belt around someone's stomach and make them and force them to eat less food.

Well, obviously these therapies don't work. Over time, we see these medications, these second generation drugs like naltrexone bupropion, fentrametopyramide, even the early daily injections of agonists called liraglutide, all we really saw was, you know, 3, 9, 10 percent of body weight loss on average across the board.

But the thought was at least in some people. So I have people who have lost hundreds of pounds on all

of these medications. And this is, this is also what I, these are FDA approved medications. I should also sort of mention on the side that there's medications we've used that, as I said earlier, are used for diabetes.

There's amlin agonists called Simlin, which is a pramletide. There's SGLT2 inhibitors. There's metformin. And Topiramate and a cousin of topiramate called zanisimide is a migraine medication. These all have been effective and studied in randomized clinical trials to help with, with body weight loss. So you have this whole array.

The question is, how do you figure out what medication to use in what person, which I think was another part of your question. And, and that's where we really get into thinking about. How can I help this person? If all the drugs are the same in terms of their efficacy, how do I, how do I choose what medication?

And really there's several things we look at. One being a dual effect, you know, if you have a

migraine headache and you want to lose weight, well then maybe Topiramate is helpful. Um, if you have diabetes and you want to lose weight, maybe, uh, one of the, uh, GLP 1 receptor agonists like liraglutide or dulaglutide would be helpful.

If you have more of a hedonistic effect, you have more cravings and wanting and, um, sort of addictions to food, you know, we think about Contrave, which really helps with that hedonistic brain. And so that's the way we've largely practiced obesity medicine. But then again, three years ago, it's been sort of flipped a little bit on its head because all of a sudden, you have 50 to 100 percent more efficacy in a drug.

That has implications again, uh, beyond just the adipocyte or the fat cell. So really exciting in, in, in that sense. So let's spend a minute just talking about the effects of GLP 1, um, because, you know, that's, that's one of those metabolic effects of bariatric surgery that we, you know, we learned was beneficial for weight loss and insulin

sensitivity and all these things.

And as you say, now we're kind of targeting it, but what is the effect of GLP 1? Why is it so effective? And why is it more effective than some of these other medications? Yeah. Great. And, but again, you know, it's, um, first thing to sort of, talk about is the, the, these agonists, again, I, I first prescribed in 2005.

It's called Exenatide. It was twice daily injection. Then Liraglutide came along a couple of years later and it was a once daily injection. Everybody loved that. Then Doolaglutide came along in, in about 2014 ish. And that you know, it's called trulicity. That actually you only had to inject once a week.

So what the, the drug development was trying to do is you know, no one wants to poke themselves more than once a day or no one wants to poke themselves in general. So how do I, you know, get to something that is a little bit longer in duration? Through that development of adding a fatty acid molecule and other things, changing around things in the G L P

one.

molecule. These, these drugs, you know, have sort of like a 97 percent analogy to the GLP 1 molecule. So by manipulating that, they were able to have the drug target, not only target the brain as it does, it, you know, works in the gut as food goes through your gut, this GLP 1 is released, but it has an impact in the brain and the hypothalamus.

But if you attach fatty acid molecule to it, it stays in the brain. It penetrates the brain longer. And so that's why you see more efficacy. You have more central action with the GLP 1 molecule. And the GLP 1 molecule actually forces us to eat less food. We have a reduction in food intake and actually then has implications, regardless of weight loss, on all the organs.

And so we, we know that it. It slows gastric emptying. We know that it has indirect effects. So there's not a GLP 1 receptor on liver, but we

know it helps fatty liver disease because it decreases inflammation. When you shrink that fat cell, you're reducing systemic inflammation or inflammation throughout the body.

Uh, we know that the, these, this molecule affects has pleiotropic effects. So it has effects beyond just It's effects on body weight loss in other organs like the heart, like the brain, like the fat cell itself. Um, and, and that's what's exciting is that it's not just the weight loss. So we would, we would say that if you went on a diet and lost 100 pounds, why be on a GLP 1 receptor agonist?

Uh, and lose a hundred pounds. It's probably the same, but it's not. So you're having an effect beyond the weight loss with these medications. So Scott, you mentioned a little bit about that decreased intake and that decreased sensation. So a couple of things. First of all, what does the patient feel? And in addition to that, do they have, you know, we know that there's some medications where they had a lot on a

diarrhea or anything, or what is that all about?

And then what is the typical average? I know there's a wide range out there and depending on the medication of expected results. And then can you talk finally a little bit about the side effects of these medications? Yeah. You know, I think in taking care of the, you know, thousands of patients that I've taken care of over the last almost 20 years, you know, you hear the stories and you're always asking your patients questions and you know, primarily I think people would say, okay, well I'm just going to ask my patient about hunger, but we know that, you know, hunger is something you, you want to have.

It's not, it's not devilish. We don't want to wipe out hunger when we. Um, but we want to sort of temper, uh, things like hunger. So hunger and appetite reduction is one of the, some people feel full quicker. So if, if drugs like these GLP 1 receptor agonists, uh, reduce stomach from the food contents to empty from the stomach, you're going to get a

sense of, uh, feeling fuller.

But what I've noticed over the last couple of decades in using some of these medications is that, uh, especially with, you know, medications like topiramate early on, was that in some people they said, you know what, I, I just don't think about food that much. And that was interesting to me because I married an Italian woman who where food is everything and I would never want to take away someone's food noise or their thinking about food of what the next meal is.

But you can imagine the spectrum of that food noise that some people, it becomes really intrusive and affects their food choices, their food habits, their food timing. And so, they didn't realize they had it, but when they put on the drug, they're like, wait a second, I guess I'm, I'm not thinking about that enough.

So, what we realize is that these drugs not only have an impact on appetite regulation, like fullness and hunger, but it has multiple other implications in other parts of the brain that control our food

preferences. That include, uh, food noise, as we were just talking about. So, really interesting when you interview a patient after on these drugs, I ask a lot of those different questions.

Secondly, um, these are, right now, these are the most highly effective medications and for the next five to ten years we will see, you know, three to seven drugs come out. That will have even the same efficacy or even greater. So let's give some numbers out there. So again, the second generation drugs that I said earlier, Atrev, Usimia, Orlistat, early daily injections like Victoza and Succenta, these are all the brand names of liraglutide.

And so these basically would have about three to 9 percent body weight loss. And that's subtracting the placebo arm in the clinical trials. What we see with the long acting semaglutide, which again, I think to frame this, everything these days is called Ozempic, but Ozempic is just one drug that has been

around since 2018, which is, only was at the time, only one milligram of semaglutide, this once a week long acting GLP What we saw in 2021, in the summer of 2021, was the higher dose of semaglutide now, you know, called, uh, Wegovy, was 2.

4 milligrams, and then it had a significant effect. So Ozepic itself doesn't have that much, maybe 7 percent body weight loss. Wegovy, higher dose of semaglutide, 12. 5 percent when you subtract the placebo arm, or 15 percent in total. And then you have in 2022. The approval of dual agonist called terzapotide, terzapotide, which mimics not only GLP 1, it mimics GIP, GIP is another gut hormone and that together produced on placebo subtracted 20%.

So you saw in these trials a remarkable difference in terms of

efficacy. And again, if you think about sort of categorical weight loss. More than 35% of people on the higher dose of semaglutide lost over 20%. Uh, 63% of people on tirzepatide lost 20% and a quarter lost over 30% of their body weight. And so we're beginning to see effectiveness that's equal to metabolic bariatric surgery, which is quite remarkable when you're only manipulating one molecule or one gut hormone.

And so really important to understand the degree of, of body weight loss There. Obviously like all drugs, it comes with side effects. So by inhi, you know, reducing the stomach from emptying, you're gonna see a reduction in food, uh, leaving the stomach, so it's gonna sit in your stomach. So you see a lot of GI side effects like nausea or vomiting.

It can affect gut motility. These, these both mono and, and dual agonists, semaglutide, tirzepatide.

And so you see some people get diarrhea, some people get constipation. But again, what I've found in my patients, because I do a lot of nutrition counseling, Uh, by reducing fat or reducing fiber in the first few days of these drugs, I really don't have many patients who have side effects.

Obviously there are people who do and I'm not going to say I'm some kind of a potion magic man here but it seems that I've reduced some of that anecdotally in my population of patients. Um, that said, there are other things that can happen. People get a little tired there's, uh, things that I would mention for the population, uh, the read, the listeners here.

would be that pancreatitis is often put on, uh, or, or thyroid cancer is also put on some of the conversations around these drugs. There's been no evidence that there's an increase of pancreatitis in clinical trials with these medications. Certainly, we have to look out for people who have medullary thyroid cancer, uh, and MEN syndrome, which is a multiple endocrine

neoplasm.

Two, uh, it's one and two, but the second version is something that you would want to avoid these drugs in. But again, relatively tolerated by larger pop parts of the population. So, uh, really good, really good drugs. What about the, um, some long term, you know, uh, uh, safety profile of things like Ozepic?

I mean, you know, it's very popular right now. We'll see headlines, you know, people are going blind on Ozepic. Osepic face, osepic butt, you know, address some of these kind of longer term concerns. Yeah. And thanks for bringing that up. Yeah. We have to, again, realize that the, the larger population around the globe has now really managed people who have obesity.

So it doesn't really fully understand the effects of body weight loss. But you know, as you, as a bariatric surgeon as people have seen after metabolic and bariatric surgery. Um, with the effects of weight loss come changes in, in our body fat. So you have excess skin and excess

skin can look like, uh, you know, sagging of the skin and people's spaces.

And then it's often, uh, can misconstrue it as, you know, something that's negative and, and maybe somebody has, you know, some kind of problem with, with it, but it really is just an effect on body weight. Um, so, and I think some of the pushback is. Let's, let's calm down a little bit.

These are great drugs. Looks like they're here to stay, but let's not put everybody on their mother on it because we haven't looked at long term data. As I said earlier, there's 20 years of data that's been out there. This drug has been studied for many decades. Uh, you see, you know, probably the most recent data that I would point to would be something along the lines of the effect of semi glutide on people who have established heart disease.

So, as many of us in the medical field look at not only drugs or other, other treatment op, uh, treatment options for for obesity and other metabolic diseases, it's

really looking at the effect on major adverse cardi cardiovascular events. We call this MACE. These MACE criteria are important to look at because it's looking at, What is the risk of someone developing a major cardiovascular event, which could be have, you know, lead to death?

And so they've done a study, five year study of people who have already established disease. So they've already had a heart attack. They've already had maybe a stroke or even a peripheral vascular disease, which is an implication that you're having heart disease. So they took this population, they put them on the drug and Um, study them for five years and actually showed those people who are on the drug have a 20 percent reduction in developing one of these major cardiovascular events.

So we see that with metabolic and bariatric surgery. Caused about 40%, but here's a one drug in a population that caused 20 percent reduction. So, um, I think anecdotally there's probably longer

data, but here's one trial five years showing and the side effects, as you were saying, are there. Some people it's, it, the blindness is more along the lines of if you have somebody who has, um, disease in their eye related to their diabetes.

We do see some of those individuals have a worsening of their, their eye disease related to their diabetes. Um, but that is not something that would happen in the general population. So I just wanted to quickly address that. But I think that's important to say about the heart disease. And then I would say, uh, the implication on other metabolic diseases.

I mentioned fatty liver disease earlier. So there's trials that have shown their improvement in fatty liver disease. There's trials that show that there's improvement in kidney disease, which is important in people with diabetes. And we know that obesity is an independent risk factor for kidney disease.

And we see heart disease, heart failure. All these studies have been done with the drugs

that manipulate these gut hormones. And it's all been really positive. Scott, as we wind down here, two quick questions. You mentioned before that, you know, this is drugs that we're all chronic drugs have, you know, taking these medications for chronic disease.

And so what happens when the patients come off? And then is one of the things we touched on a little bit earlier is. How do we go hand in hand with surgery? How do these drugs fit into that profile? Because, like, like, I'm a colorectal surgeon, IBD patients, you know, we work with our gastrologists all the time to, what's the medical management, what's the surgery side of the house, how do we work together?

So, can you touch on the patient, what happens when they stop taking it, then they go right back and get on the weight, and then the role of the kind of combined multidisciplinary therapy for these patients? Great, great question. Um, so as I mentioned earlier, You know, if you stop the medication your, your disease is going to come back.

Um, you, we, I think we all have to have an understanding that obesity is a

disease. So we, we can't say that there goes, and we, we have to have language around that that speaks to the effect of disease. So it's a person with obesity, not an obese person, not a fat person. We have to stop with the pejorative language that's existed in our medical community, specifically our medical community.

Okay. We have to treat obesity as a disease. When we treat a disease, we have to understand that there's a spectrum of that disease. So there's people who maybe just need small dietary interventions and can, and can resolve their obesity. There's some people who need, uh, to behavioral change, who have you know, eating behaviors and other things that that alter their, uh, body weight.

Some people need, uh, medications that we've largely talked about, and then some people need surgery. But just like cancer, you think about people who have cancer, you're a colorectal surgeon, you take the cancer out, but then somebody needs chemotherapy. So we have to understand that the disease of obesity may not be, may not go away.

You

may not change that person's set point. To a regular body weight with just doing metabolic and bariatric surgery that they still need treatment of that disease. Before, it was thought that, well, you haven't changed your behaviors, I gave surgery, and if you still have obesity, well, it's your fault. Now, we realize that it is obviously, you know, maybe you needed a medication to, to hit another target.

We think that metabolic and bariatric surgery hits multiple targets around that way. So again, if you're giving a therapy and then you take it away like a drug, that disease is going to come back. We see that in hypertension. We see that in hypercholesterolemia. We see that in everything. We've just never had the mindset in obesity to think that someone has to stay on the medication.

So, I, I think, you know, specifically to your question, you take the drug off, absolutely someone's gonna, uh, have a weight regain. It's not their fault. It's the drug being, uh, not on board anymore.

We see that because of these drugs being put on over the last three years, then their insurance doesn't cover it or the coupon is over or they can't afford it.

They have to go off it. And we see this all over the place over the last three years. So, your question about the, the implications beyond And looking at combination therapy, I think largely I'd want our, our listeners to understand that if you think and believe that obesity is a disease, it's a chronic disease, you're going to need chronic therapy.

So if surgery is what is needed in the beginning because of the severity, the complexity of the disease somebody may need a medication. Uh, or they may need to continue to see a psychologist, or they may need to continue to see a a registered nutrition, uh, nutritionist, dietician nutritionist. So you know, I think the multidisciplinary group is essential for treating the treatment of obesity.

And that's what we've done here at the Cleveland Clinic. We've, we have an area that focuses, a clinic that focuses on, uh, obesity, the metabolic, excuse me, the Bariatric and Metabolic Institute.

And we have an array of treatment options for patients. And so, as we go forward, I think, you know, surgeons are realizing that, you know, they can do a very good job in treating obesity and obviously there's a pathway if someone is not responding well or still needs treatment.

Now that we have some of these very effective, uh, medications. So do you see the patients, so, you know, I work at a bariatric center, we have a bariatric pathway. Where do you fit into that pathway? Do you, do the patients see you first, or do they see the surgeon first, or is it very, or just practically, how does that work?

Yeah, so I'll give you the, sort of, how it works and how it should work. Um, how it works now is that you, your treatment of obesity is dependent on who you see. Okay. So, you see a dietician, you're going to get some dietary nutrition counseling. You see a psychologist, you're going to get CBT, uh, if you see a surgeon, if the indications are there, you're going to get surgery.

If you see a medicine, uh, obesity medicine specialist like myself, you're going to get a medication. The treatment of obesity has largely been developed that way. And also, and obviously, bariatric surgery has been so effective and still remains the most effective treatment for severe obesity. Uh, there's been bariatric and metabolic clinics, you know, scattered throughout the world for, for many, for several decades.

And now you see the growing subspecialty of obesity medicine, but there's only 200 of us in the last you know, 17 years. So it's not a large group of individuals who are trained in obesity medicine. Certainly there's people out there who do the certificate, who take a test and pass the test.

But they may not have the experience that those who are trained in obesity medicine do. All of that said, I think what you see moving forward is just like a treatment of every other disease. It should start with medical therapy primarily first. If the severity and the

complexity is such, metabolic and bariatric surgery is absolutely a first.

And so, there's probably, and should be, different tracks. You have people based on certain criteria that, that need metabolic and bariatric surgery. But then there's those, and now with these effective medications, highly effective medications, that probably should start a medical path first, and eventually, certainly may go to surgery and, and do, but you, uh, but, but I think that's where you'll see the majority of people begin.

There's also endoscopic therapies, which we haven't talked about today, too. So we have a gastroenterologist who's doing endoscopic therapies. We have metabolic and bariatric surgeons. We have dieticians, psychologists, and people like us. And so you have all those people under one roof, which is perfect.

And then really the, the challenge I think for our field as a, as a whole is to, to have standards of care and, and algorithms that speak to the,

these criteria. It's not going to be based anymore on just BMI. We're going to look at visceral adiposity, fat around the gut. We're going to look at metabolic complications of obesity.

So I think that's where we're going, you know, down the road. You hit a very important, I think, like, system based problem there, and that's, there's, there's not enough of you. And that's the problem that we're, I'm finding in, in our community, in our system, is, is, it's very difficult, actually, to get these patients on these medications.

There's, there's a prior authorization obstacle course to even get them started on these medications. So, for those that are outside of the, the mecca of, of Cleveland Clinic, who should own this process? That's a problem we see too. Should it be primary care? Should it be an obesity specialist? Should it be the bariatric surgeon?

Who should own that process and how do we navigate that? Do you see that changing? Are

insurance companies going to come around and it's going to be easier to get people on these medications? And Scott, before you answer that, I want to jump in and say, can you also touch base on the rise of these? Like we see on some of the companies for erectile dysfunction or depression or anything that you can just go online and all of a Sudden they come to your door.

You don't even have to quote unquote talk to a doctor in person to to tag on to jason's question What role does that play in this particular field? Yeah in both perfect questions You know, I would say if you didn't ask that question, you should watch south park episode on obesity Which is fantastic and really gets to the point of the health care system Where we are in the larger community of taking care of obesity and, you know, I've been in this, this game for a long time.

I've been a very strong advocate and have changed laws in different states and also nationally. Uh, there's still a lot of change that needs to be happened. But Jason, to your question about, you know, the difficult, Cleveland Clinic is not a unique case here.

We are very challenged. We're a bigger system.

So we're even more challenged with a lot of these obstacles. I think you, you stated it perfectly. This obstacle course, again, is largely based in stigma and bias against people who have obesity. The thought is right now, insurance companies uh, people who run hospital care systems, they can't see farther than their own noses.

They're so focused on the financial implications. Of these these medications that they cannot foresee the future benefits of weight loss and all the array of implications. Not only medical implications, but think about self confidence. Think about work force and, and doing, uh, going to your work, not having, you know, difficulty moving.

There's so many implications downstream. That is ridiculous not to cover these medications across the board and it can't rely on a dumb economist to do some stupid

simple, uh, equations to predict this because medicine, as we know, it's not physics, it's physiology. There's multiple spectrums of benefits down there that we should see.

All that said, as I said earlier, we have a rebranding of a squashed wellness community That is trying to make itself in the obesity space. Largely relying on people who are desperate, who want to lose weight, who are not well informed, and want something, want their autonomy. They want to make the decisions themselves.

So you have telehealth, which is a great platform which we all use, and you have a weaving in of the business savvy wellness industry that gets you your, your wellness, obesity care. But you're not getting somebody who knows anything about obesity. You're going to get somebody who is not going to understand what

drug to use for how long, what its implications are, what the side effect profile is.

To your point, Scott, you can just sort of sign up. I can get, I can, I can get my erectile dysfunction medication. I can get some hair, uh, treatment and now I can get a semi glutide, uh, injections from somebody who doesn't know anything out there. And this compounded industry is really taken off. There's no evidence that compounding versions of these medications are effective.

We do not know their side effect profile because they've never been studied. It's not to say that they can't be used and they don't have an effect. But we just don't know the side effect profile. And somebody who's practiced in the state of, of Massachusetts for so many years before I came to the Cleveland Clinic, I, we all know about the compounding disaster, pharmacy, compounding pharmacy disaster in 2012 that led, you know, over 750 people died because someone just tainted the product in the compounding pharmacy and all of a sudden in an unregulated system you had,

you had death.

This is obviously more regulated now. You have these 503. Uh, B pharmacies that have some regulation around it, but we don't know any evidence right now of the effect. Um, that said, that's what, that's the challenge in, in academics like me who practice obesity medicine and also you Jason, who is looking for a partner.

How do I know this person knows what they're doing and how do I ensure the safety of my patients? And I think that's the challenge that we're going to see for the, that that's, that's grown out of this post pandemic telehealth and sort of, again the combination of telehealth and rebranded, uh, wellness industry.

So where do we go from this? We need a tiered system. We need, uh, we need a system that not only allows primary care providers to take care of obesity, which they should, but they need to be educated and informed. of how that works. Then you have a second tier system, which largely is what you see.

Cardiologists, surgeons.

Um, psychiatrists, OBGYNs, hepatologists, uh, endocrinologists, all can now begin to manage obesity regardless because it's part of their spectrum and it complicates their own diseases that they naturally, that normally take care of. So we need to educate and inform them. And then you have the top of the tier, which is people who have expertise in the area.

And that's people like ourselves. And again, that tiered system will go from community hospital to. to, to larger institution, just like it does in every other disease, but that's the way I'd frame it, I think, for the future. So Scott, last question. Give us a look into that future, whether it be with obesity medications themselves or, uh, you know, something else that's on the horizon.

What's to come? Yeah. I think just piggybacking on what I just said, Scott, you're, you're going to have a system that now is going to include highly effective anti obesity medications, which will have anywhere from 10 to

25 percent body weight reduction. So there's a triple agonist right now that we just studied here at the Cleveland Clinic.

It's been studied around the country. It involves. The GLP 1, GIP, as I mentioned before, because that's terzapatide, and now glucagon is plucked into there. So that triple agonist called retatratide is highly effective, uh, up to nearly 25 percent body weight reduction, 24 percent body weight reduction.

Uh, with that drug. So you're going to see numerous drugs hit these, uh, these targets within the brain and within the gut. And these again are nutrient stimulating, uh, hormones. We call them nushes. So that includes not only GLP but we have glucagon, amlin, which I mentioned earlier, and you're going to see combinations of those, which are now being studied in phase two, phase three trials.

And then

you're going to see other combinations with drugs working at other targets, whether it's looking at the muscle, where there's drugs that won't look at the muscle, there's drugs that, the drugs that we continue to use now. So you're going to see multiple combinations, which befits a very complex disease moving forward.

That's on the medical side. On the surgical side, as Jason can point out easily, is that you're going to see less, less invasiveness. You're going to see endoscopic therapies probably do something as well. And then again, combinations of those. But my concern, Scott, is, is that you're not going to have a healthcare system that, that reduces its own bias.

I think there's a larger awareness of providers. There's a larger awareness of patients over the last three years because of these drugs. And, you know, there's, there's, there's, um, more stories about it, but there's still a lot of bias that deflates the benefit. And you have this telehealth, uh, compounding slash wellness

industry, uh, that's cropping up.

So you're going to have a lot of challenges in the next three to five years as some of these drugs come out of where to go, who to go to see, how do I use these therapies, etc. that is still going to be a spectrum of care. I think it's going to turn into progressive obesity care, and there's going to be a lot more change, but you have to invest in not only research, which has largely not been invested in, you're going to have institutional buy in to have people run obesity departments or obesity divisions.

You're going to have to have people accept that this is a real disease and that may take some time. Well, on behalf of Jason and myself, as well as all the listeners, we would like to thank you so much for just an amazing journey and really enlightening, uh, podcast to walk us through this. And for those of us who are out there, And if you want more from Scott, he also was a guest appearance on the Oprah Winfrey show and that's special.

So

you can find him there. So we just, we just didn't bring somebody in off the block for this particular one. But Scott, once again, thanks so much for joining us here on BTK and we hope to have you on in the future. So appreciate it very much. Yeah. Thanks Scott. Thanks Jason for the opportunity to talk and we'd love to come back on at any time.