Ozempic and the Obesity Revolution

I got that burger, man. It was awesome. I I love that place, >> dude. Burgers are the That's my weakness, man. I can I can eat the especially the smash burgers, >> dude. They're good. >> But nothing beats the goat chop at AAS. >> Fair. Fair, dude. >> And Houston has so much good food.

Like you can't just I can never keep up uh with the restaurant scene and there's always like you you go to one restaurant after a long time and then you you get there and you're like, "Oh, finally I get to try this." and then you read some article or some blog and guru newer one that opened up I was like you know catching up to the restaurants but you're >> I know you're already out of style there's always something new that's for sure man >> what are what are some uh man there's so many restaurants but what are some good uh couple of restaurants that you've been to recently what would you say are your top you know restaurants in Houston >> gosh you know one restaurant that like you know even like 10 years ago when I was here for med school um I loved this spot the Hobbit Cafe I I think they have some of the best burgers in Houston, there's just such a huge variety.

I mean, they have like every kind of meat you can imagine. They have the burgers like Greek style with taziki in them. They have Mexicans uh southwest style with jalapenos, the standard mushroom Swiss style. All in, you know, the the vibe in that place is pretty cool. It's kind of Lord of the Rings themed. Um all the burgers are named after some Lord of the Rings stuff. Um you got statues of the movie and book characters.

So that the place is just a cool spot and they I mean they have like over 40 burgers on the menu. All of them are awesome. >> You know, speaking of burgers, I think one of my absolute favorite restaurants in the city is uh NY's Hustle. And NY's >> I haven't been there, >> dude. It's It's one of like it I' I'd say it's top five in Houston. And NY's Hustle has this burger, which is which is amazing. But they have other things, too. They, you know, they do interesting stuff.

They use like techniques from South Asian cooking, from Turkish, and they they use new American style cooking. And they just use the multicultural makeup of Houston to create the food there. And this just it's just amazing. They have this thing called the Nancy Cakes, which is this fluffy cake that they have and they put salmon row on it >> and this they it's it's freaking dectable. You know, you have to have it. >> Dude, I'm getting hungry just thinking about it. >> No one can go wrong with aas.

I mean, that's, you know, the absolute. >> Yeah, Agas is the OG. That's for sure. >> I mean, if you're South Asian, you know, in in in the US, you know about agas. like people fly in from other other states to go to AAS and and and try the good chunk there. >> Dude, every time every time my parents come in to to see us from Dallas, I mean, pretty much every time we're getting AAS. >> Yeah. And then the other one that, you know, um I think both of us have been to is Nobies. >> No is good.

>> I really like Nobies because they do really good like they they have this uh the pastas, the breads, that's amazing. And and that's that's one good one. But the other one that a lot of people don't know about, but it's it's really highly rated. It's called Theodor Rex. >> Dude, you talked about that a lot. I haven't checked that spot out. >> You have to go to that place. That place has this thing called the tomato toast, and it's I can't explain it. It just You have to try it.

>> It doesn't sound awesome, but I'll take your word for it. I'll have to try it. >> Yeah. >> Blueorn is also a sweet spot. I really like that place, >> dude. Blueorn. Oh my god. I Yeah. So, Blue Dorn, I mean, this is classic steakhouse, but they also have the classic like that pot pie thing they have. I mean, >> lobster lobster pot. >> Yeah, it's so good. >> It's so good. The the the last one I kind of want to hit on is one we went to together uh with a group of other friends was Neo.

>> Oh, dude. The omocasi. >> That was one of the best meals I've had this year, you know? >> Yeah, that was awesome. I think we can keep going about the restaurants, but Neil is Neil was one I just can't forget sometimes because I was like, you know, when um you know, I do want to take Miam there one of the days because once uh we're done with the you know uh uh you know then she's ready to go to the sushi restaurant, then we'll go and we'll have some some good. >> Yeah. Yeah.

Dude, that that place was cool. The the chef was also awesome. I mean, his story is really cool how he traveled all over the world and even met that guy Hero um the Netflix famous guy Hero Dreams of Sushi. uh and learn how to make it. I think that was really cool. >> Yeah. You know, the the best thing I you the thing that I like about the new age of restaurants is they're focused on, you know, this the fresh farm-to-table food, growing the produce locally, uh sourcing their food, right?

And that's a big thing missing in our society, right? I mean uh having fresh unprocessed food, making the pasta from scratch, using the right kind of you know uh ingredients because obesity has been on the rise you know since you can say like in the past 50 years 60 years the the rise of processed foods in our country has made it really difficult for people and people have gained and ballooned up you know it's >> like crazy man. Yeah.

I mean our whole society like the rates of obesity and overweight even not just obese but overweight. I mean they've skyrocketed like 50% plus the population is overweight. >> Yeah. And the food quality I mean the stuff that we grew up eating I sometimes look back and see like I I knew kids were eating Lunchables for lunch at school and remember Lunchables that's the most processed. >> It's like such garbage food, >> right?

And like all those snacks like fruit rollups and gushers and Fritolay chips, >> the cereals that we uh eating, >> I mean, Lucky Charms and Co like the the Cocoa Puffs and you know, uh >> Toast Crunch, all of them. I mean, yeah, it's >> highly processed and there's no there's no doubt. I mean, look at look at the way society is. I mean, you know, people have gotten obese. People are less active. You they're sitting in front of the computers. They're they're gaining weight.

Now I I do like the trend of this this new trend over the past few years of people trying to take care of more of their health and I think um a lot of online media and online podcasting and has a huge role to play and people focusing on their health and sometimes people can be misled as well, right? >> Yeah, they certainly can. I mean people are definitely more interested uh and there's these alternate forms of media that are making it more public.

People are very keen to take their health and their fitness and all of this stuff into their own hands. And there's a growing sense of like avoiding unprocessed avoiding processed food. Kind of what a lot of these restaurants that we were talking about do. They make it from scratch. They take pride in the preparation of the food and sourcing it from wholesome ingredients. Um it's all about that same trend about being healthy and avoiding excess weight loss, excess weight gain. >> Excess. Yeah.

Obesity is a trillion dollar industry, man. And now with the you know the advent of new obesity treatments I think it's the exciting space as a cardiologist is very exciting for me.

I've been working with a lot of these medications over the past you know 3 years four years as soon and I feel like I'm I've been on the on the cutting edge of things where I get introduced to a lot of the new of these new medications that are targeted towards weight loss just because of my work in cardiology and in clinical research. So, it's a very exciting time for me cuz I'm learning a lot. We're learning together as a society of what these medications do as well. >> Yeah.

I mean, it's fascinating. You know, everyone has heard of these drugs like ompic and majaro and stuff, even though they may have initially been created for diabetes and blood glucose um control. They've basically mass market appeal for weight loss. And it's not just weight loss. I mean, it's it's control of your metabolic state, right? And I I think it's fascinating. I I see it in, you know, as an orthopedic surgeon, so many of my patients are on it.

Um, people have lost tremendous amounts of weight. Uh, and it's not just like the actual amount of weight that's lost. There's so many effects that it has on your brain, on satiety, on appetite, all of that stuff.

I mean talk talk a little about that like what what do you think when a patient comes to clinic just taking like a real life example like when would you suggest or talk to a patient about a medication like for for instance ompic or any of these there's so many different types >> yeah so you know uh a big part of uh cardiovascular health that I think we've talked about in the past is metabolic disease and metabolic disease is your waist uh not as much as BMI I think BMI was >> has had been for a long time uh target of uh you know way to measure your your your weight against your height and see are you obese or not but many people have large amounts of muscle and their BMI might be higher right uh but uh I think waist circumference is turning out to be a bigger indicator of your cardiovascular health where uh waist size over 36 in can be high risk uh you know people who have uh uh metabolic um induced fatty liver, right?

People who have metabolic disease and because of that they have fat accumulating around the liver that's causing liver dysfunction and that's one of the most frequent causes of liver disease. Now um you know things like um high triglycerides and high lipids that that's causing a lot of cardiovascular disease and because of obesity people are developing uh insulin resistance which is a precursor to diabetes.

is when you start developing insulin resistance, it's it's a cycle that leads you to becoming a diabetic which comes with a whole host of diseases afterwards including you know uh retinopathy which is you know your retina getting disease neuropathy you know cardiovascular disease which is vascular you know vascular disease so you know that's when I see patients kind of inching towards metabolic disease or have metabolic disease inching inching towards these endstage diseases that's my first indic medication that hey, we have these uh medications now that I can urgently use to kind of reverse them and pull them back from where they're heading towards.

So, for me, it's been a great tool and a lot of my patients have benefited. Man, I I can't I mean, you know, we still don't know the long-term effects of some of these medications. I mean, they've been around for a long time, so we have a good idea they're overall safe, but there's they're not free of side effects, right? >> Yeah. No. And I So, I'll I'll jump in there for a moment.

I think that's really interesting that you know in terms of how you think about these meds for your patients, how you prescribe them, how you talk to your patients about them, it's really focused more on the metabolic aspect rather than purely the weight loss. Even though that's kind of the the hot button and the hype topic is how much weight loss can I get? Can I lose weight? Is this a tool for me just to get more fit to shed those last little bit of pounds?

More so is the potential positive metabolic effects. the weight loss is obviously a plus um but it's not even necessarily a primary effect. >> Yeah. So you know the story about how uh the these these medications were discovered. I mean people have known about the GLP uh one receptor for a while right? But the hardest thing was uh to find the analog that would you know uh activate that receptor. And the way, you know, uh, it's funny.

They the way they found out was there this there were there's a there's a type of animal that's called hila monster. It's in the southwest region of the US or in Mexico. And they find that they noticed that the hila monster uh only ate few times a year and it survived in those harsh conditions without having to eat too much.

And when they isolated some of the venom that the hila monster has, they found that there are GLP like uh you know uh there's a there's a chemical that could activate the GLP receptor and that was the precursor to the first uh type of GLP-1 medication that was produced. It was called Biotaa, right? And that was the Biotaa was the first type medication where initially it was for diabetes for glucose control but then they started seeing some some weight loss of that medication.

the appetite suppressant nature of that medication and that eventually led to the formation of seven wut you know there were some other >> that's awesome that like uh you know like translating this stuff from you know an animal model I mean there so much research involves rats mice dogs things like that but like studying it and seeing something that's totally different and then applying it to this like that hila monster poison I think that's fascinating you know this this is something that's funny um so when I was a little kid a hila monster is like a lizard that lives in the desert, right?

When I was a little kid, you know, like I don't know, two, three, whatever years old, you know, sitting at the table, I had a little placemat and my parents wanted to make it fun. So, one of the placemats I had was desert animals and it had, you know, like desert hairs with the long ears, desert falcons, and then one of the animals on there was a Hila monster. And, you know, I'm a little kid. I was like two and a half, whatever. And my parents at the time only spoke to me in Udu at home.

So, I didn't know any English until I went to kindergarten. Uh, and you know it was every animal's name was on there and it was spelled G I L A. And I thought it was like, you know, my parents at the time they didn't know either. They thought it was Gila monster. And so I learned the name Gila monster. And Gila in Udu means wet. And I thought like forever when I was a little kid, I was like, Gila monster, it's just it's always wet. It's just like there's water everywhere. It's in the desert.

I didn't understand. And I just looked at my mom and I was like, Gila monster gila like it's very wet. I would like be wiping it with a tissue every time I sat at the table with that place, man. So, the the Hilo monster has made a full circle in my life. It's now it's now brought up in my podcast. >> You're talking about it on your podcast and it's a it's a medication that cancels a lot of your surgeries. >> I know it. Yeah. No kidding, man. No kidding.

The Gila monster is the culprit >> leading to surgical cancellations. That That's something too. I mean, this is like a fight with the anesthesiologist. Sometimes you have a patient who needs surgery like I'm doing a shoulder replacement or something and a patient's on ompic or mjara or one of these medications and new guidelines are coming out all the time and I feel like every hospital has different guidelines.

Every individual anesthesiologist the day of has a different opinion on oh you need to stop this one 5 days before this one 7 days before this one 2 weeks before. It's like h how long I mean how long is that potential delayed gastric emptying and all that stuff? I mean do we even know since these are short acting long acting? They're very different medications. >> Yeah.

They, you know, they started noticing as the as the the these medications grew, they started noticing that people are having a little bit of increased aspiration events because, you know, when when the stomach transit the the transit of the food is slow through the stomach. If they even had not eaten after midnight, they still had some residual food left over and that could lead to aspirations after anesthesia.

But you know we've been saying these names and there's a lot of confusion uh about these names and what is ompic what is mangjaro what is wiggoi what is zebound so you know let's let's talk about what these medications are you know these are incrurtinbased therapies incrretins are different uh receptors or or you know molecules that are present in the body that are that are activated or produced uh in response to food or nutrition coming through the stomach or the small intestine. Right.

So there's four major type of incretins that we've been targeting lately and one is GLP. All right. One is GIP. Uh one is amalain um and there's a few other uh you know um uh incretins but the main most of the medications um have been kind of towards targeting either GLP gip or most of them are activating these these receptors.

The GLP1A is G GLP-1A is like semaglutide right semiglutide is purely a GLP1 agonist and it activates the GLP-1 receptor right now semaglutide uh in its generic form is semiglutide but there's a diabetic form of it which is called oenthic right and the semiglutides weight loss version which was marketed towards just weight loss and not for diabetics is wig goi is the same exact compound they're they're not any different same liquid if you broke the the pen and took out the compound.

It's the same exact thing. It just marketed the same way. The semiglutide is wiggoi and oanic. Now the other one is uh you know trespite which is which is a glp1 agonist. It activates GLP1 receptor just like this semiglutide but it's also a gip agonist you know and it activates two different types of receptor. GIP is another receptor that you know works in glucose metabolism and satiety where it tells your brain to stop stop eating because you're full.

It has some effects directly on fat metabolism as well. Um so that's one of them. So that's trespound which is purely for weight loss. You know that's what it's marketed as not that it's a different compound and the other one was mjaro. So the two major ones on the market right now are semiglutide and trespide and these two uh brand names are uh one targeted towards weight loss and one targeted towards um the diabetes portion of it.

Now each of those medications the semaglutide has an oral form called ribbelis and the trazepite also has a oral form coming up called orphogluteron. So that's the two major ones.

One is produced by Nova Norris and one is produced by Eli Lee and you know the that's been a big fight lately of you know who's are big they've been the biggest competitor in the space where is Noah Norris going to win is Eli Lee going to win >> so those that's >> yeah know that's really interesting I mean you know because we hear these names all the time right like patients on one versus the other it's like is there a benefit is there not um is their side effect profile different is their weight loss different um and it's interesting to know I mean like the actual receptors they act on and potentially act on multiple receptors because you know we're so we're using these terms like agonist antagonist agonist is just something that mimics a molecule and acts similarly at a receptor that that's really what an agonist is and a lot of this whole pathway about fullness and regulating weight loss that all these medications act on obviously they act in our gut our intestine um in an incrretin fashion like is talking about to stimulate these receptors um but they also affect the speed at which your gut empties its food.

And that has big consequences because there's a lot of stretch receptors inside of our gut. And when those stretch receptors, they're neurons that you have, what's crazy to think, you have as many neurons in your gut as you do in your entire spinal cord, which is kind of kind of wild. But the the gut nervous system, the entic nervous system is remarkable. And so with these stretch receptors, you are consistently full. The gastric emptying is slowed and it expands. And it remains expanded.

It sends a signal through those entic neurons up to the brain to stimulate satiety. Another thing that stimulates satiety, right, is that especially with these more long acting medications, these peptides, they can cross into the brain and they can stimulate directly the receptors in the brain for satiety as well and control of your appetite. That's why it's not just the fact that you're losing weight. You're actually not feeling hungry on these medications.

And it's even stimulating beyond just satiety and feeling full and not having an appetite. It's stimulating how much pleasure you derive from appetite. And that that's something I found very interesting when reading about these medications is the positive feedback that we get, right? You eat something that's delicious, you enjoy it, you want to eat more of it. That's a very common thing. But it somewhat eliminates that.

Um, and it can make a lot of things that are formerly addictive not addictive. Like that. That's a an interesting note with these medications that even people that are smokers like cigarette smokers, it's actually been noted in a lot of studies that people stop smoking who are on these medications because that similar brain loop, that similar stimulus and positive feedback cycle you get, these medications act on that and they stop that or they diminish it. I thought that was very fascinating.

>> Yeah, it's very interesting.

I have a lot of you know patients that I've started these medications on and initially you know the feedback that I get from a lot of them is hey you know I just you know just food is not as exciting anymore for me you know a lot of people say that I don't have the food noise like some people were like hey you know before I used to eat my breakfast and I would start thinking about what I would have for lunch and now I just don't those thoughts don't cross my mind anymore so it suppresses that food noise as well right now same goes for a lot of addiction pathways where you know um uh Since it's suppressing that desire for food, it does I've noticed a lot of people have cut down on their smoking quite a bit.

This they tell me, hey, cigarettes are just not as as exciting for me anymore. Not I'm not craving it as much more alcoholism, you know, uh people have reported to me personally in my experience that, you know, hey, I don't drink as much anymore based on that. Now, the side effects of that as well, you know, some people do get depressed on these medications sometimes.

I'm not there's not clear I mean you know when through the trials there's a lot of careful monitoring of people uh um mental health and a lot of people with severe depression are excluded from the trials uh but uh people do feel a little sad because before they used to get the pleasure out of the food that they used to enjoy and sometimes maybe that was one of the few daily pleasures of their life you know uh and now they don't have that anymore so that sometimes can make some people sad and that's these are just more anecdotal findings as Yeah, I know it's interesting.

I mean, the the positive effects are are certainly there in terms of metabolic control, weight loss, and even suppression of some of these addictive potential things like smoking or even getting addicted to eating excess food, right? Gluttony. Um, but the side effects are concerning, right? Like, you know, if you read the side effect profile of any drug, the fine print, you can start getting worried.

But something that I think is relevant and happens to a lot of patients on these is sarcopenia, right? muscle loss, losing lean mass in addition to just the desired weight loss in addition to just fat weight loss. What have you seen with that when you have patients on this? Like what realistically is the amount of weight loss? What do you talk to people about in terms of their muscle mass and maintaining muscle mass while on these drugs?

Yeah, that that is that is the case and you know in the large scale studies they do studies where where they measure uh body lean mass through dexa scans as well and a lot of studies are then way people take these medications and then they lose weight and their bone mass and muscle mass is measured through dexa and uh from my understanding and some of the reading I've done is uh of the of the trial is through semiglutai there was around uh 33% uh lean mass loss the the total amount fat loss or to total amount of weight loss out of that 33% was lean mass loss or non-fat loss right with trappepite it seems to be a little lower around 25% of it was uh non-fat loss as well um now what I've seen and through the clinical trials uh you know with semiglutide there's around a 14 to 15% body weight loss a little less maybe 13 to 14% loss and then diabetics is a little less than that.

With trespite, you're seeing sometimes anywhere from 17 to 20% loss non-diabetics and a little less that in diabetics as well. So, Tresepide does have a little extra weight uh increased weight loss and a little less of non lean mass loss as well. Um what what they've done in the past is they done studies in you know they they did studies with GLP-1 and it showed that GLP-1 by itself causes a significant amount of weight loss.

Then they studied uh studied the GIP alone GIP agonist by itself and the weight loss was m there but not as much but when they combined them the weight loss of them together was very synergistic and it was much more enhanced than than just each of them alone. >> So what what do you think could be some strategies to prevent that?

Like I um you know from the muscular skeletal perspective obviously the muscle loss is concerning because muscle loss is very dangerous for overall body health and your frailty index and muscle loss is going to lead to skeletal failure a fracture right because it's going to lead to bone mineral density loss um there's some studies again this is not consistent some studies haven't shown any real link between like osteoporosis and these meds but some have and I I think just in general a lot of patients are not on them for long enough yet that a lot of these medications are newer and they keep coming out newer form form.

So maybe it's just time will tell and maybe the patient population is not yet old enough to get real fluorid osteoporosis while on these meds. But it's a worry I have and I I wonder how to counsel patients who are on these medications for good reasons. Metabolic control and weight loss is a good thing. How to maintain your lean mass and selectively lose or try to selectively lose fat. >> Yeah. Uh you know that's that's a that's a true concern.

I always have a conversation with my patients that when I put them on these medications, they're going to promise me and we'll have a check-in about strength training. Um, you know, every week or every time we do dual escalation. I really want them to do strength training, weight training. Now, I don't know if that's helpful. I mean, that it is helpful. We know strength training is helpful. I don't know if it's counteracting the effects of the the the lean mass loss from these medications yet.

And honestly, we don't know the answer.

a lot of there's a lot of and I go to a lot of conferences and I do a lot of clinical trials with these medications and we don't have the exact answers of what that means long term right uh some of the other things to consider when you counsel patients I mean any kind of neuroendocrine tumors that they've had you know um menary thyroid cancer or any kind of pancreatic cancer is complete contraindication and you should not if you have any uh history of men one men two uh the the multiple endocrine neoplasia disorders, you should not take these medications.

Likewise, if you have any history of pancreatitis or chronic pancreatitis, you should not be on these medications. Uh you know, if you're if you've ever had inflammation of the pancreas, you know, uh that's excluded. Uh anyone who's too frail, too weak, uh already has osteoporosis, I try to avoid uh these medications in them because I don't want them to have that, you know, significant weight loss. >> There are things being done to counteract that in the future.

um you know some of the so we talked about the you know the GLP1 GIP so GLP1 you know by itself can increase the insulin in the body so it lowers your blood blood glucose right uh it decreases your appetite it decreases your gastric emptying right the gip itself um it does have a little effect on fat metabolism so it is a little bit more target towards the fat so when you have the GLP combined with the gip that's why you see a a little bit more fat loss >> and do those medicines do those then the ones that are combined do they also have less lean mass loss or it's it's not it's not a change on lean mass >> no no it is so so that's what I was saying is around 25% compared to semiglutides >> 30 33% >> okay >> lean mass loss so the GLP gip medications have a little bit less lean mass and I think it's getting better now >> that's good so they're they're basically able to make them more selective and that that's where the research is going right >> it is it is and then uh the other receptor that you know we talked about amilin as well uh uh there are medications nova nordis is coming out with a medication where they're combining uh semaglutide with uh with kangride which is uh amlanin agonist where they're targeting amin receptor and that has possibly has less side effects of nausea and gastric emptying you know uh possibly we don't know yet uh some of the it's early studies and possibly less muscle loss as well.

But the other promising medication is reatride and reatride is uh it's GLP-1 agonist, GIP agonist and glucagon agonist where it directly targets the glucagon receptors and glucagon has you know a direct effect in fat metabolism a much more faster. It uses fat as energy rather than using your you know protein as energy or carbohydrates in the blood or sugar. So, uh, that medication does possibly tend to have a little bit less fat loss as well or less lean mass loss as well. >> Interesting. Okay.

So, by hitting that, it it basically tries to select out more for fat loss, which I guess that makes sense. I mean, glucagon, you know, to bring it back to a little high level, I mean, glucagon is basically a hormone that's released kind of in the starving state, right? a state of we call it starvation, but when you're fasting or you haven't eaten for a while and your body needs energy stores, so it selectively will be released when the glucose is low.

Um, and it leads to fat metabolism like the beta oxidation of fat. Um, so that's pretty cool that they can selectively target that and kind of shift it more towards fat loss and less towards kind of general mass loss. >> Exactly. So that's why it's a little exciting. Now I in my experience I I am doing a lot of trials with redatite as well.

Uh so you know some the fat loss is pretty profound uh and people are losing a significant amount of weight but it does come with a little bit more side effects and that's that's the big um you know issue that I've noticed is uh the weekly injection and taking that medication and and having nausea for at least one or two days uh a week u you know is can be very taxing on some people and and maybe after a year year and a half of doing the medication they get tired. >> And let me ask you this.

So, how bad is that nausea? I mean, is it bad to the point that they're having to take medications like Zopran or something to mitigate that or is it mostly just you kind of just feel uncomfortable like a nauseous feeling and you're not really vomiting? I mean, how how bad is that side effect? >> Yeah. So, some for some people some people that side effect can be uh pretty significant and some people don't even feel it, right?

So for some people the side effect can be uh just a little bit of nausea when they see you take a little bit eat a little bit of food. Um you know maybe one day of feeling a little tired, a little under the weather.

Uh but and that gets better with taking Zopran or eating a little bit more high-fiber diet, low smaller meals uh rather than big large fatty meals, you And that's a part of the counseling that we do where we talk about, hey, make sure you're eating short small meals that are high in fiber, high in fruits and vegetables, less greasy, less fatty foods. Right. Some people just have minor side effect, but some people have pretty significant side effects.

I've had people I've seen in the hospital that have ended up there because they just couldn't stop vomiting. >> Wow. uh and and that be terrible. >> Unfortunately, unfortunately, a lot of the side effects that we're seeing is from a lot of these um compounded uh medications that have uh been distributed in the market.

uh you know there are somearmacies they're compounding these medications uh especially with semiglutadide and transepide uh comp compounded mix with B12 or some other things and somearmacies are doing a good job compounding and their medications are effective but some are not and it's not being regulated right there's no body that's regulating those these are not FDA approved compound medications and they're being uh given to patients and sometimes these patients have severe side effects and almost I can tell you almost always when I've seen a patient end up in the hospital in the ER is with a compounded seminal glutide or compounded.

>> Right. Right. You know, you know that kind of begs the question of cost too. I mean a lot of these medications are very expensive and it's a question does insurance cover it or not? what is the so-called indication for the medication? And you know, a lot of people get these from other countries like I I remember when I was um we were I was on vacation a few months ago.

I went to Cabo with u my my wife and son and um we were just at the airport and one of the little local kiosks at the airport was selling I think I can't I think it was Mojara it was one of these medications but I think it was Mjaro specifically. Um and dude people were buying them like crazy. I mean, people had bags that they were taking with them because it was so cheap there in comparison to trying to get it here in the US.

And you know, after I saw that, I like talked to a bunch of people like I just remarked on it that I thought this was an interesting phenomenon. And people were saying, "Oh yeah, I know people that do that." Like that's a thing. Like they will go on purpose to places like Mexico or Turkey or wherever to get these meds and then come home and either use them themselves or I mean I guess sell them, you can call it black market, whatever.

Um but it's I mean whenever there is a overpriced item especially with early research right things are always more expensive uh people are going to try to subvert it and and do what they can.

>> Yeah I mean these medications are extremely expensive you know uh a lot of my patients want to do cash pay uh and a lot of times cash pay can any can be anywhere from $350 a month to $500 a month for the for the ph directly from the pharmaceuticals idially or no one order selling them directly to the patient. They can be around $500 a month.

Now, the compounded ones can be sold from anywhere from 175 to some people I've even seen paying way more than the actual medications like $650 or $700 a month because that's they just don't know. They just are getting told by a lot of these physicians or pharmacies that hey this is my semiclutin. I'm selling it and this is effective. And you know, I'm not going to lie, there are some very effective ones.

And there's people that have lost a lot of weight on some of these compounded medications, but it's unreliable. And uh now people are also starting to sell the compounded reatride, which is in phase three trials, but we don't even know the long-lasting effects of from from largecale clinical trials, but is being sold as a compounded medications in some of thesearmacies. >> Yeah. I guess they're they're capitalizing on people's like desire for a rather quick result, right?

Um you know, most people that are buying this are doing it for weight loss. Um that are not getting it through their physician. Um they just want to see results. I mean, they they're maybe unaware or they don't care as much about the potential side effects.

Yeah, the side effects, you know, a lot of these online websites like HIMS or hers um you know some other there's one called fellas and all you have to do is answer a few questions online and you can get your compounded semiblutide or transepide in the mail but um I personally advise my patients against that. You know, it's kind of like a similar um a similar thing with like marijuana dispensaries.

You know, I don't know, like 10 or so years ago, those were just kind of coming out, maybe even more than 10 years ago, but you would go in and you see kind of a doc in the box. You answer a couple questions. Oh, are you depressed? Or, oh, are you lethargic, whatever, or you're in chronic pain? Okay, here is a prescription now for medical marijuana. It was just like a dime a dozen. and you have a BS survey that checks off the so-called boxes needed to legally prescribe it. It's a similar thing.

>> Yeah. Yeah. You know, but that that weekly nausea and weekly just feeling like, you know, the first day after you take it, just feeling a little tired, nauseated, that just takes a toll on it. So, there's there's interesting medication and I'm um also part of some of the clinical trials for that is um through Amgen and Amjen is creating creating this medication which is once a month. It's a once a month uh weight loss medication and interestingly it's a GLP1 agonist with a GIP antagonist.

So it it inhibits the GIP receptor which has had similar effects and pretty significant profound weight loss. But the interesting part is through some of the clinical trials the nausea only lasts a couple of days on the first dose but then the whole month you have that the continued weight loss which is kind of exciting. You know it's you know Amigen is a company that's that's been uh big into create creating antibodies.

It created a medication called Rapatha which as cardiologists use that uh in in um for cholesterol uh lowering therapies in people who have had heart attacks. And since they have this expertise in antibodies they they have this antibbody um you know backbone that's attached that allows it to uh stay in your body much longer, right? And that way you can have it in your body for one month and you know you take it once a month and it's it has a similar weight loss to the other medications.

So what I tell my patients is sevenutide uh you know trespite where it was iPhone 1 and iPhone 2 you know and and now you're >> the iPod touch >> iPod touch and you're about to see the explosion in this market where there's all these types of companies that are working on so many compounds. I know estrogenic is working on it. There's Viking Therapeutics. The Chinese have gone into the game as well and they have come out with their obesity medication as well.

So there's a lot of exciting work going on in this space and this is just the beginning of obesity treatment.

I mean I think it's fascinating you know the the the other interesting thing I think is like when you talk to people about this a lot of people are curious um like why it has to be injected you know and now more oral medications are coming about but like even when GLPs were first identified I mean this was in like the early 1900s u not not long after insulin itself was discovered GLPs were known they just couldn't stay around they were very short acting because they're just short little peptides they're nothing but little chains of protein molecules.

That's all these things are. And you just couldn't stick, they couldn't stick around. And so you couldn't actually have them exert a reasonable enough effect, hit that threshold level needed to actually have something meaningful occur. Um, and that's what a lot of this pharmaceutical research has been is creating these longer acting medications that now can last long enough, their half-life is long enough that they can hit enough of those receptors to now exert an effect.

Um, and since they're peptides, that's a big problem, too. you're taking it orally because when you eat anything, your stomach acids dene, meaning they destroy the protein molecules and so these medications, they go through your mouth and your gut. By the time they actually get to wherever they could exert an effect, they're toasted. So that's why a lot of them have to be injected into the bloodstream.

Um, a lot like you're mentioning, these new oral medications obviously found ways around that, which is nice, so the patients don't have to stick themselves once a day, once a week. >> Yeah. Yeah.

the the oral medications are usually once uh you know it's a pill form and the two big ones is one one of them is already on the market it's called ribbelis which is oral semiglutide uh and it's being used mainly for diabetes treatment but there is a little tiny bit weight loss component to it anywhere from uh 6 to 8% and the orphoglyeron which is being produced by ely and that has a pretty significant weight loss not as much as the injectable form but a lot of people are thinking about these pills as a possible future uh maintenance therapy for people who do lose weight because one thing with these medications is once you stop using them the weight does come back.

>> Yeah. The rebound effect right >> the rebound effect is much uh longer. Now interestingly uh the the rebound effect from from semiglutide was a little bit faster.

Now with trespite a little slower you know and with uh this this new some of from what I've read in some of these MJ medic the longer acting medication they last in your body longer the rebound effect is a little slower so the the medications that are lasting in your body a little longer have a have a longer halflife they they do last a little longer and the weight loss is not as much but I I see the potential of these oral uh weight loss medications uh as as a maintenance therapy in the future where people can take a pill once they've lost that weight to maintain that weight instead of having to inject themselves constantly.

So that's that's exciting. >> Yeah, I know that is you you know one thing that um it's interesting just to think about I I don't know the answer or what it is but like insulin in general is an anabolic hormone like it it builds up your body it can lead to weight gain but it also is a critical component for muscle gain. Um, in fact, one of the most common cocktails for professional athletes or bodybuilders and stuff that you know is so-called take steroids, right?

That's the the common phrase, but when people are on those, they usually it's a cocktail of testosterone, growth hormone or IGF-1, insulin, and then ariththropotin. Um, the last just being increasing red cell mass so that you can carry more oxygen in the blood. But insulin is critical. It's needed in order to build muscle. And I find it fascinating that all of these medications being incretins, they by definition agonize.

They stimulate the receptor to increase insulin production, but at the same time, you're still getting loss of your lean mass. And I I I think that's an interesting phenomenon that maybe there's some amount of threshold level needed or that it's missing to hit the muscle gain or anabolic effect of insulin and it's just able to stimulate enough to keep the glucose in check but not let it go above a certain amount. I don't know. I mean I think it's interesting the way that I think about it.

>> Yeah. You know in my experience people who are injecting insulin they tend to gain much more fat, get get gain weight. you know, weight loss is much harder when you're on insulin. Uh, but there are medications being developed now that do completely suppress the weight loss and they're early trials. That's why I said it's iPhone 1 and iPhone 2 right now. There's exciting medication.

There's a there's a medication called bimagromab and it it it's being it's somewhere in the phase 2 clinical trials and what it's doing is it's targeting the active receptor and what that prevents is is muscle loss and they've seen that medication being combined with some of these GLP1 agonist and is is showing a purely fat loss with maybe some muscle gain component to it as well. So that is a very exciting prospect. I know we >> sounds like the holy grail is fat gain muscle by taking a pill.

>> It is the holy grail but nothing what I' what what I've realized uh in in in in the practice of medicine is there's no such thing as free meal. Uh and there's always some kind of u you know u >> there's no magic bullet. >> There's no magic bullet. You know, who knows?

Maybe this could be I I do think there's a lot of long-term effects of it, especially with the concerns with bone loss, weight loss, nutritional deficiencies, and a lot of people are losing a lot of weight and they're not maybe uh taking the right kind of nutrition. Like, you know, you've seen that in in those patients that go through the beriatric surgery, right? I mean, some of those patients do really well.

They get off all their other medications, they lose tons of weight, but some people just keep losing weight and they become uh severely nutritionally deficient. A lot of them have B12 deficiencies and folic acid deficiencies. Uh they get severe anemia. Uh >> yeah, frail frailty is a big risk, especially those patients that lose massive amounts of weight after buriatric surgery. That's for sure.

>> So have you have you come around people who've had beriatric surgery in the past and what their bone quality looks like and what their muscle quality looks like? I mean, have you have you noticed that in your practice at all?

Yeah, I mean you know patients after buriatric surgery uh quite a few of them I won't say most or all but a lot of them who have had a history of beriatric surgery they can become quite osteoporotic um it just affects your stomach and your gut's ability to absorb um adequate amounts of nutrition right because it just eliminates your ability to intake your calories um and patients can get very protein maln malnourished and protein deficient and protein as we know is the building block for the muscle and muscle is critical for skeletons uh to maintain their bone mineral density.

So yeah, I mean you see that a lot patients that have prior buriatric surgery now they have a fragility fracture. Yeah. Yeah. So I worry about that right with these people that might be on it for a long time lose a ton to lose tons of weight and might develop some nutritional deficiencies unless they can uh get the right kind of weight loss right kind of nutritional counseling as well. The other the other concern is the concern for gastric paralysis.

I mean is that a point at some point where we continue taking these medication over 10 15 20 years at some point would our guest gastric emptyings really slow down and cause us to develop gastroparesis? Uh I don't know the answer to that yet. >> Yeah, that's an interesting question right like could could basically like your stomach I mean it's a muscle. Could it atrophy? It gets so delayed and so conditioned to be slowed and emptying. Could it actually atrophy in some way?

And I mean that that would be a big problem. >> Yeah. And and and with that with that, you know, I always have an exit plan with my patients where we talk about this when we're starting uh that, hey, eventually want to get you off these medications.

Uh, and maybe once you get to your target weight loss, maybe let's let's kind of decrease the dose and maybe uh decrease the frequency of these medications as well and see maybe we're taking it maybe once every two weeks, once every 3 weeks to kind of maintain the weight loss and maybe you continue to exercise, build those good habits, do strength training, um, build muscle, do cardio as well and and and build the good habits to sustain that weight loss so we can maybe completely get you off the medication cuz I personally don't want anyone to be on on the med on the medication for for the rest of their life.

Now, what at some point it might get to a point where we're only taking these medications every 6 months or every once a year and that's sustaining us throughout the year. And that might be a a good option because obesity is a is it is a disease. It's we know that some people can eat a lot of food and not gain fat and not not get fat and some people can sometimes be on a perfect diet and not lose weight. And obesity primarily is a disease.

For some people it's very hard to control and obesity brings on more u you know need to eat your you know your the leptins uh are suppressed and that you don't uh get full as fast and you know and you keep craving food. So we'll see where where it goes. >> Yeah. I mean obesity really is just like a a disease that causes a failure of your metabolism like you can't regulate whether it's brain mediated, GI mediated or or combination.

You just can't control whatever that axis is of keeping your metabolic rate high enough and you just add and you maintain you hold reserves of nutrients in your body and that's how you gain weight. >> Yeah. You know, but the only right now um Wiggoi which is the weight loss medication semiglutide is the only medication that's uh approved from insurance companies uh for uh cardiovascular disease and reduction of cardiovascular disease. So that's the one I've been able to prescribe a lot more.

So I have the most experience with that >> because there is a cardiac indication for that but you know some of the medications like Zebound now have indications for sleep apnnea and I think a lot of them will get cuz I'm doing a lot of those cardiovascular outcome trials so I think a lot of them will eventually get the cardiovascular indication as well but uh uh interestingly a lot of these GLP1s gip medications are becoming uh cardiac medications and people know that cardio cardiac disease is the number one cause of death in the world in in in our country especially and weight obesity is is a big component of that and uh that's why cardiology is being targeted.

The one one big aspect of cardiology that's being targeted is uh this this this phenomenon called heart failure with preserved ejection fraction where you know we have heart failure where the heart is squeezing well you know the heart is not weak but it's not relaxing as well because of obesity because of the fat around the heart and weight loss has significantly shown to improve the relaxation ability of the heart to be able to expand easily and intake a lot of the blood so it can squeeze well and um I'm seeing a lot of improvement in that heart failure with preserved ejection fraction those patients who have heart failure even though the heart is not weak uh with these medications.

So that's that's exciting for me because heart heft as we call it did not have any real any real uh treatments as of yet. >> That's pretty awesome. I mean you know these medications are kind of like a a revolution in terms of the ability to treat metabolism. I mean it's like insulin was discovered in 1922. Um so just a little over a hundred years ago um basically the first medication that was able to regulate metabolism in some way was invented and now we have so many more.

I mean the the speed with which science and discovery advances is crazy. Like an initial spark when insulin was found and I mean really like changed completely the lives of all those patients with type 1 diabetes. It was basically a death a death sentence. Um you now you have these medications that are helping so many people in the population. They're not perfect just like insulin isn't perfect. It has other effects too but it's pretty remarkable. >> Yeah man. Uh it's exciting.

And then you know I talked about hep you talked about type 1 diabetes. Now the other big condition that uh a lot of people struggle with a lot of people have is fatty liver disease.

you know nash or as we now call it mash metabolically uh mediated st hippat hippatosis you know I can't speak >> it's a hard word >> pretty much fatty liver that is because of metabolism and these medications are at the forefront of treatment of mash now where the fatty liver is completely being reversed because of the significant weight loss cuz you know before people would have fatty liver and doctors would just go lose some weight you know like go what do you mean lose some weight how like what what do I do?

Uh, you know, but now, >> you know, but it was it was vague because doctors themselves didn't know. You know what I mean? Like doctors had no clue how to really counsel patients on what is weight loss, what is exercise, what is a good diet. Just like you're left to your own devices. Go figure it out. I'm just telling you, be healthy. Go to >> be healthy. Go eat right. Go eat right. Good luck. Go >> find out how. Let me know. >> Yeah. Like the patient would be so confused like what do I do?

I've been doing everything. But now, you know, MASH is becoming treatable with some of these uh, you know, weight loss medications. And that's that's exciting because a lot of people might >> end up not getting the liver failure that they get because of the severe obesity that they have. Uh, and with weight loss, their mash nash could be reversed. So, that's exciting as well. So, I think it's it's it's uh exciting, but I would like to caution.

I mean, you know, there there's no such thing as free lunches, and we'll see where things go. But I think I'm going to be using these uh medications in in patients that urgently need it, but maybe it could add many more years to their life, which might be heading the wrong direction right now.

So, I'm going to use it until I I see something alarming or otherwise scary because without these medications, some patients might not have a very long life left because they're very metabolically deranged and their their cardiovascular health is heading towards a place where things might not be as easy for them in the future. Yeah, it's like a ticking time bomb.

I know me personally in terms of these medications, I'll continue to uh have fights with the anesthesiologists when they want to cancel cases. No, I'm just kidding. I mean, it is what it is. Um, but it's just funny, you know, from uh from the perspective of surgery, and it's not just me being an orthopedic surgeon and like goofing off about it.

like it's so common with all surgeries that the number of cancellations um because a patient is on these medications and the uncertainty around it um is remarkable. But that's what happens with anything new, right? The advent of new technology creates uncertainty. There's more questions than answers when something new comes about because people don't know how to use it. That's something that it's so hard to predict. Here's something new.

We have an idea what it does, but how it's going to be utilized. Like these medications initially for diabetes, just like the next step after insulin discovery, but they're being utilized for so much more. >> Yeah. Exciting times ahead, man. Well, we'll we'll until then, we'll keep uh hitting up some of the Houston restaurants. >> Oh, yeah, baby. Try it out. I got to check out Theodor Rex. >> Yeah, you should. You should, man.

I think we can do another episode on just the restaurants that we like. >> Oh, dude. We should. We should. Maybe we'll do it from the Hobbit Cafe. Their burgers, man. I'm telling you. >> You know, I I don't think I've been there, so I'll have to >> Oh, really? >> Oh, dude. There we go. We got one each. >> All right. Perfect. >> All right, guys. Thanks for tuning in. We'll see you next time. Two docs, one mic. Bye.