Obesity, GLP-1s and Dermatology

Welcome to season two at Derms on Drugs of Video Podcast brought to you by Scholars in Medicine, the best educational platform in dermatology and provided no cost medical providers. Derms on Drugs is where cutting edge dirt meets hit or miscomedy. A med virus from Dr. Dermatology in each week. I'm joined by my residency buddies, Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh. And we use our 60 years of combined derm experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be on a cutting edge of Derm and you'll actually have some fun listening. New episodes drop every Friday on Scholars in Medicine, Apple Podcasts, Spotify and other major podcasts platforms. And a reminder that there is a video component that has the key figures and tables from the articles that we talk about every week. And this episode is supported by Lilly, a medicine company. We are so excited this week to have Dr. Shanty Narla with us from the Medical College of Wisconsin. And we are going to get into obesity in dermatology. And we couldn't really help it. Like we were super excited to finally do an episode. We're going to talk some about GLP ones in dermatology since everyone in the world talks about GLP ones all the time nowadays. So before we get into Dr. Patton and Ferris' first articles, I wanted to just talk very, very briefly about kind of the role of obesity in inflammation. And so just to give it everybody very quickly up to speed. Right. So you've got these things called adipocines that are basically cytokines released from fat cells. There's one called leptin, one called adiponectin, one called chemorin, one called resistant, one called omentin. And then IL-60NF alpha, CCL-2 and IL-1 beta are also produced by fat cells, adipocytes in psoriasis, leptin directly drives IL-17A, adipose tissue, directly releases, resistant, TNF, IL-6, jackstap. It doesn't release jackstap but can drive it. There's decreased adiponectin that down regulates T-reg. So my play role in atopic dermatitis. There are adipose macrophase ages that switch from M2, which is anti-inflammatory to M1 and pro-inflammatory. And then there's this M-TOR, which is mammalian, targeted of rapamycin-1 that is related to fat, might be relevant to psoriasis and H-S as well. And obesity affects the skin and the gut microbiome. So it, they're just wanted to, I know that was really quick, but just wanted to give people kind of an idea of the mechanistic way of how we think of fat as affecting inflammation and immunologic diseases. So that out of the way, let's go ahead and get started. So Dr. Ferris, what do you got? Okay, so I have a recent paper published in the British Journal of Dermatology, GLP-1 receptor agonist and reduced mortality, cardiovascular and psychiatric risks in psoriasis, a large-scale cohort study. So if we're going to talk about a large-scale cohort study, you know, it's probably going to be trinetics, which is, yes, from a US, so it says a US database, although it's in the British Journal, but we do still have the best databases here in the good old US of A. Biggest databases, the best databases, the most complex databases. Beautiful databases. What did they look at here? They looked at adults who had psoriasis and obesity or type 2 diabetes, all of whom were on systemic anti-soriasis medications. And then they looked at them sort of split them into two groups, GLP-1 receptor agonist users, like semi-glutide, Lyra-glutide, and then other metabolic meds for diabetes or weight loss, things like metformin, SGLT-2s, sulfonoluria, so, you know, those drugs. And so they did propensity score matching and came up with a little over 3,000 patients, and each group matched for demographics, comorbidities, insulin use, and followed them for two years, and the outcomes of interest were mortality, mace events, psychiatric events, and autoimmune sequelae. So, you know, what do we not have? We don't have things like PASI score, so we really don't know disease severity. We just know enough, severe enough that somebody put them on a systemic therapy. So what did we find? The GLP-1s actually had a pretty significant reduction in the comorbidities that we talk about a lot in our psoriasis patients. So if you compare patients on the GLP-1s versus those on the other diabetic or obesity drugs, all cause mortality reduced by about 78%. Yeah. I know, I know. So it's 78% reduction, right? This is still going to be a rare event. Mace events, 44% reduction. This was driven like the two big ones, stroke reduced by about 65% heart failure by about 45%. Those were the two that were statistically significant. They also threw in their alcohol and substance abuse, and I think this is interesting because there is evidence that the GLP-1 receptor agnus also, you know, they basically give a signal of early satiety. So it's like they decrease your craving for food, but there's some evidence that they also decrease craving for things like alcohol and drugs. So a 65% reduction, and again, you're looking at coding for alcohol abuse and 50% for substance abuse as well. So decreasing shots of insulin and shots of alcohol. I'm always looking for a bad joke, bad dad joke. That was a very funny joke. That reminds me. Have I told you guys my farmer joke? No, but let's hear it. It was about the best farmer in Ohio, like literally one in a ward for being the best farmer in Ohio. He was outstanding in his field. Yeah, okay. I don't know that the GLP-1s can do anything for a stency humor, but it happens. So they did. Yeah, go ahead. The biggest thing that kind of struck me about this. So in that one, like forest plotty thing, they showed the impact on all of these things in people with psoriasis versus the impact on people who don't have psoriasis. Yes. And they have bigger, you know, because this is all stuff that you think of the GLP-1s is probably help with anyways, but it had a bigger impact on all of that stuff even in psoriasis. In psoriasis, then people would not on psoriasis. So I guess it's maybe a little more and I was wondering about that too. I mean, we think about this as being like a very, you know, talk about all the inflammatory mediators. We know there's a lot of systemic inflammation associated with obesity. We also know there's systemic inflammation associated with psoriasis, even a non obese patient. So I was kind of thinking it's the double whammy of two causes of inflammation. And so, you know, potentially to me that would suggest that there's actually an anti-inflammatory impact of the drugs, not just obesity reduction, but or, you know, you're so inflamed when you've got bad inflammatory disease, you know, think about like H.S. You know, those patients, you just look at them and they you feel like they're so they've got rampant systemic inflammation. You look at CRPs and patients, you've got bad H.S. or really bad psoriasis, you know, they're off the chart. So that was kind of what I took into that. So definitely, do you, because the question to me has always been like, okay, it's because when the days started coming out that the G.O.P. ones really helped with psoriasis. And so this is not, we're not looking at, do they help with psoriasis and this already went to the comorbidities, but similarly, you know, trying to dissect out the, is it just you lose weight? So your healthier versus the G.O.P. ones having direct effects on the stuff that we're just talking about, you know, to the G.O.P. ones affect the adipocines, you know, separately from just, you just, you know what I mean? What do people think about this? So that's like the million dollar question. I think that we run into and also when I looked at this study is that, so right now, basic science-wise, I think even just starting with are there G.O.P. one receptors on keratinocytes? You'll see very conflicting evidence. And then when it gets to psoriasis, so I think there was, there's one paper that's always cited in a lot of the G.O.P. one, like skin disease papers. It's the mention of how they took, I believe it was psoriasis, human biopsies of psoriasis, but they see that like gamma delta T cells were found, like they were decreased, I'm not completely remembering the gist of it right now. But from that paper, they make this, you know, hypothesis that the GLP1 receptors that are found in the skin are found on these, you know, T cells or killer cells. And those are migrating to the skin and they're not necessarily on the keratinocytes itself. Okay. But I don't think anybody knows the exact GL, like I think GLP1, honestly in my brain, is kind of like depylliamab. I think it's just magical. It works on a lot of different things. And no one actually knows how it works. And so I feel like GLP1, if you look in the literature, there's like, oh, GLP1 modulates the, you know, conversion of M1 back to M2, which is anti-inflammatory in the macrophages. You'll see, oh, it works on these natural killer cells. It works on these delta gamma cells. It reduces TNF alpha, IL-17 and whatnot. But I think that goes back to both of the questions that you and Laura were asking, is that, yeah, I think there is anti-inflammatory effects. But like when it comes to us, right, psoriasis, atopic dermatitis, HS, those are all metabolic, syndrome, obesity. But in my mind, it's like the chicken before the egg is this severe obesity. That is predisposing you to these skin conditions. And by helping the obesity, helping the metabolic syndrome, is it, you know, helping your psoriasis and your skin disorders, or is it a combination of both? And I think that's where we really need like more basic science to help us out. I don't think we're just going to be able to, from doing like chart reviews, observational studies. I don't know if we're ever going to be able to separate those in the way that we want to. I think like prospectively following these patients will be helpful. So one of the things that they did look at was like, what is their impact on other inflammatory disease? So they did say that they did not see a reduction in fatty liver disease, sleep apnea, Crohn's, ulcerative colitis, UVitis, or interestingly incident, psoriatric arthritis, although I believe I've seen studies that suggest that, you know, GLP1 use can be associated with reductions in incidence of psoriatric arthritis. So they go to be really interesting as ever time. Like if it's, you know, do you drive like reduction in the incidence of psoriasis? And I don't know that I've seen that study, although it may be out there or somebody will be doing it tonight and try netics and put it out there. I think that's interesting that you mentioned that because now one of the GLP1 inhibitors I think is FDA approved for liver disease, for match. Yeah, for, yeah. Yes. So it's like why aren't you seeing why did they see what they're doing? Why did you not see it in that population? I think it's the devil's and the details. And you know, also they only did the GLP1 receptor agonist. So they didn't do the newer like combined GI, like chersapotide, which has two targets. So, you know, it's like we're going to need to redo all of this when we, as we have more and more drugs that have different targets, you know. And we know that like for example, like the chersapodide, you know, weight loss is way more, as it seems to be significantly more effective than just like the GLP1, you know, receptor agonist. I'm assuming it's because there's two targets, although that may not, I'm not an expert in that area. So I think it's going to be interesting as we have more, like a lot of these have Lyroglutide which was sort of first generation and probably not, I think a drug that's not used quite as often anymore. Yeah. So educate me just in the very basic way of like how to GLP. So there is a normal protein in your body called GLP1. This is correct. And it when it is elevated makes you not hungry. That is the basic idea. So it's actually when you take in, I wrote this down because I had a feeling that someone was going to ask me this question. So I wrote it down here. I have, you know, I wrote it down. I have, I can go, I can literally read off the things that I've written too. But essentially GLP1 and GIP1, they're in curtains. So essentially what that means is their hormones that respond to increased, like sugar, increased food intake. And so what happens is there's this whole concluded pathway, right? The main activity of GLP1, GIP1s, or especially GLP1 is they release insulin from your pancreatic beta cells. And then you need to decrease glucose. But there's receptors. There's GLP1 receptors on actually a lot of organs. Brain, heart, kidneys, liver, pituitary, it's everywhere. So there's a lot of blood in the blood. Like did they, do we know if they excluded, like if you're on a JLP one and a TN. if they didn't count you. If you, so when they compared those two, and this didn't make any sense, but if you look at the category, the columns, it was like, okay, H.S. patients on the GLP1, what percent of them were on Adelimimab, it was zero. But the problem with that chart, and we talked about this, and it still didn't make sense to me, is the percentage of patients in the, this patient had H.S. and was on Adelimimab, the percentage of those patients that are reported as being on Adelimimab was 22.21. According to the paper, it didn't make any sense. Yeah, and that is a weird thing about how genetics report state. And I started trying to do some work with somebody on genetics, and after like a couple of you most back and forth, I was like, this just doesn't make any sense. I can't figure this out. I'm not putting my name on anything that comes from genetics, because I don't understand how they're reporting the data. And I try to get explanations, and they're like, right, that's what they said. This is just how genetics reports it. And I'm like, what does that number mean? If 100% of the patients aren't on Adelimimab, then you can't make a comparison about reduction of surgeries of patients on the GLP1RAs versus Adelimimab. So, I don't know what to make of this. That's not believable to me. It could absolutely be true. But -- Right. It's not. Yes, it quickly got hard to believe, right? So that like there was not, you know, outcomes in all patients with H.S. with comparisons. I mean, patients taking Terzepatide, not a single one had a, you know, simpler intermediate cyst repair compared to 40 in the people not take -- like it just something's weird here. Yeah. Something is weird. Dr. Narlah, what did you think of the H.S. paper? Yeah, I agree. I mean, you know, I think we can all say even in our clinics, I do see a lot of H.S. here being in Milwaukee. And a lot of my patients are on like Mojaro or Terzepatide and all these different things. So -- and it's hard for me to believe. I agree. I think it would have been a better paper if they compared Adelimab and Adelimab and a GLP1. I think that would have been -- because again, I don't think that GLP1s will ever be used as monotherapy for any of these, you know, any heart skin disorders. And so it just, you know, I agree. And it's not like they couldn't be on anything else. And you know, fair number of patients were on Clinton, Mison, a tetracycline antibiotic. And they matched those percentages pretty well. But it was -- none of them were on Adelimab compared to the people on Adelimab. And there was this huge difference that I just -- it's not believable. But I guess -- And it goes back to the Sarisis question is -- and I don't think the Sarisis paper looked at this either. Do you find these benefits independent of weight loss? If you find these benefits independent of weight loss, does that -- like do you see the patient staying on those drugs? You know, you have a -- maybe a patient who's overweight, Sarisis, you have them on a biologic, their skin's much better. You have them on this weight loss medication, and they're not losing weight. Do you keep them on it? Because you're like, well, she would show these other benefits. And I know you're not losing weight, but we showed this improvement in cardiovascular -- like I can't see that happening. I can't see the patients continuing to take the drug if they're not seeing the benefits of like the weight loss, which -- or, you know, type 2 diabetes. Yeah, I think it's hard to get patients to stay on a medication for an unknown thing. Like, maybe this will reduce your risk of having a heart attack or stroke, right? If they have something tangible, like your blood sugars are down, you're not on as much insulin, you're losing weight, your disease is getting better than that probably. I think that if it makes the disease that they can quantify better, they'll probably stay on it. Like if it's like, you would have a 35% reduction in your stroke rate, that's going to be a tough cell. Yeah. Or patients to stand. You know, the other thing that's interesting, Mack, because you're talked about being on compounded, terzapatitis, I always wonder, like, you know, these things are so prevalent out there. And so, none of these are going to be captured in trinetics, right? They're only looking at pharmacy prescriptions and pills. They're not going to capture the people who are on compounded medications. So I don't know the answer to what percentage of people on GLP ones are on the real deal, or those that are kind of getting it off the internet compounded. Interesting. Well, let's, so the, I think the takeaway from Dr. Patton's article sounds too good to be true. Probably is. And, you know, part of me thinks, you know, if you think about what we're saying, somebody who's got the wherewithal to get on a GLP one, but has never been on a biologic for H.S. And has H.S. That probably is selecting for a pretty mild H.S. group, right? So there are people who have competent to get themselves on an expensive drug. Have a horrible disease and never got on an expensive drug for their horrible disease. So it's, it strikes me that it's probably, that's got to be a big part of the explanation is, is something like that. You know, that. Yeah, and I guess I go back to like, I'd like to see incidents. So what I would like is people who don't have H.S. who then go on these drugs, you know, versus another drug. And like, does that another weight loss drug specifically? And does that, or you know, another diabetes drug, is there a difference in the incidence of H.S.? Interesting. I mean, it would be interesting to see. And yeah, I think surgical intervention for H.S. is very directly correlated with like, how long standing or how severe or how what your hurly stage is, right? Like so. So I paid this for a patient today for H.S. who was like, oh, I started going tanning and my H.S. is getting better. And initially it's like going greater, I have any lesions and I was like, initially like, so you're like, you standing in there with your arms above your head, like I've never heard of this. I didn't think, you know, tanning could cause skin cancer. And then I look at her meds and she's on Muncharo and Metformin. And she's like, oh, I was like, oh, so when did you start those? Oh, right around the time I started tanning. And now she had fairly mild H.S. to begin with. So but yeah, it was just an, it's hard to fair it all this stuff out, right? It's hard to fair it out. What like is really the underlying cause of stuff? Like it's fascinating, fascinating. So we're going to, I'm very briefly going to touch on my article. So mine was Association of GOP1 Agonist with a topic dermatitis and obese patients, a retrospective cohort study. And what I will tell you is I, I think this article showed that it doesn't work, that it doesn't make a difference in a topic, derm. What they showed was that people with a topic, derm, end obesity, who went on a GOP1 had like an 8% reduction in their use of topical or systemic steroids. So you know, given the whole trinetics thing and everything else, I'm like an 8% reduction, like in your use of topical steroids or systemic steroids, makes me be like, if there's an effect in a topic dermatitis, it is very, very minimal, which, you know, we've always kind of like everybody always knew psoriasis in H.S. like you didn't need a study to be like, that happens to people that more commonly to people who are overweight, AD is not a disease like that where you, you know, we look at it and say more likely than people who overweight. So it, yeah, once I read this study carefully, I was like, yeah, don't really buy it, don't buy it. So, Dr. Sagar, do you prescribe GOP1s? Have you, I can't imagine any derms do other than like if you've got some kind of a wellness spa or something, you know, could you imagine prescribing a GOP1? I, I can because I mean, I, I think the first thing is, you know, we see a lot of different other specialties, you know, all levels of providers prescribing them. So I think as doctors, I, or even dermatology providers, I do think we have enough training to prescribe them. And similar to yourself, Matt, full disclosure, I use a GOP1 for my own, uh, how problems of things like that. So I feel like I'm probably more uniquely positioned as a clinician scientist and, you know, to be prescribing these in conjunction with it. And, you know, as far as I know, you know, my own positions that have given me that they're not really monitoring anything other than, you know, check in with me if you have any side effects. Right. Like, for example, something that I think a lot of doctors or providers in general don't know is there is a warning. But like a recommendation, right, on Teresepatite, because it leads to delay gastric emptying, a woman of childbearing age, you're supposed to, you're supposed to tell them not to be on an oral contraceptive because that can lead, it's, it's on the product insert. Why, why? Because it delays gastric emptying of pills. So they don't get you have you don't get regular option. Correct. And so they tell you in the product answer they need to be on other some form of systemic birth control, like an IUD or patch or whatnot. Because you know how they attribute it in the beginning, the baby boom of ozempic. It's hard to say if that was from, you know, reducing key US from weight loss or is it because you had all these women who were on all our contraceptive pills and even though it was written on the label, no one knew about it. So I guess this is all to say I feel like see I had always assumed that the baby boom from ozempic was just that people were like feeling good about themselves and feeling frisky. And so there was a, you know, that kind of that's why I always the little nervous when you start somebody. I'm always surprised there isn't like a big increase in pregnancies whenever we start people on doope or like skyrezy where like people who have just felt good, ungood about themselves suddenly feel great about themselves. And yeah, thank God all he got was a cough from your brain. Fortunately, the cough drove most women away from you. You didn't really have that problem. That's good enough. Yeah, you know, we found the pregnancy before you met. Yeah. Yeah. So it's, you know, it's an interesting. I do. I've been like waffling if I want to bring this up, right? So it's interesting. There's now the deal that if you're on a certain biologic for psoriasis, you can get a monjaro right? I don't know if it's monjaro or whatever the tears up. I've tied her's repotied for 25 bucks a month. Correct. That seems like it has to break some kind of a rule. But it obviously doesn't because it's not like it's not like it's being kept under the rug. Yeah, something like that. Yeah. Like it's a, I mean, has that or would that affect you guys's prescribing of, you know, do you tell patients this? Hey, you know, we got like a bunch of different drugs. We could put you on. They all work great. If we put you on this one, you can get, you know, a GLP one drug for 25 bucks a month. Well, they have to meet the criteria, right? Like it's not like I could be like and by the way, you'll also get tears appetite. They would have to meet the criteria of having obesity or type two diabetes. So, but so do you tell where are you going to start telling your obese patients this? Like I technically by be my icon is obese. Right. So I was a BMI third just just over 30. I think 27 is overweight. I think 30 is obese. I think like lots of people count as obese. Like it's, it's an interesting thing. I don't know what you're, what do you think? You, are you going to start telling your patients who could benefit from a GLP one that if they choose to go on Tults, they can get a GLP one for 25 bucks a month? I don't think so unless that came up in the conversation. If they said I'd also like to lose weight and I, I, it wouldn't be something that I would pursue. I'm, I'm just not ready to do the GLP GIP. They have primary care physicians that have just more overall experience in managing those diseases. So I think it's, I mean, I, it doesn't make any sense to me personally that I would jump in there and be like, Hey, I know you're seeing your PCP and he's been managing your diabetes for a long time, but guess what? I can give you, you know, this, this other medication you may have seen commercials for. Like let, let's just not are. Do you have to, so Dr. Nellie, do you know about that? I know nothing about the program other than somebody told me about it and I was like, what? Is it? I think it's for private insurance. Okay. And they have to get the exochysmab approved. Okay. And then I think if it's approved, I'm not sure exactly if there is specific criteria. I think it's just if they want it, it's, I think like $25. Yeah. And presumably it would be like, you'll, you'll lose weight on this drop. Right. And you don't have to actually have an active clinical trial right now where they're also doing that combination. They do have an active clinical trial. And just so like for the audience too, when we're talking about trizipotide, there are two separate drugs, right? Menjuro and Zepbound, man, Juro FDA approved to treat type two diabetes, Zepbound, FDA approved to treat weight loss. And are there dosing differences there? Okay. It's the same exact drug. It's just that with the one with chronic weight management, which I think is Zepbound, it goes up to like 2.4 milligrams, versus with the other one, it just cuts off. That actually took me a really long time to figure out. It's the same thing with ozepic and wagobi. It literally just has to do with the dosage. That's allowed for that indication. Right. Same same drug, different dosing, depending on the indication. So in that program, do you, I mean, could Pat and say, Hey, go talk to your primary care doc. If they want to prescribe, like maybe there's, I don't know, maybe there's a handout that you can give to the patient and tell him to go see their primary care doc. Yeah. Does it have to come from the same prescriber that's doing that the talt. Right. They'd be weird. I don't know. I will say there are enough benefits of these drugs. I mean, and they are like clearly shown to look like lower hemoglobin A1c lower, like, you know, a lot of the bad outcomes that even if we're not saying I'm doing this for psoriasis. I mean, we've spent years and decades talking about comorbidities of psoriasis. So, you know, I'm not opposed. This is a class of drugs. It's turned out to be relatively safe. Right. I mean, there's some little nuances, but like, relatively safe. And we've been talking about comorbidities and we actually have data for, you know, reducing comorbidities. I don't know. Um, but I always have opposed the whole comorbidity thing with germs getting as much into it as what some of the experts on comorbidities want us to get into it. I, your psoriasis patient, yes, there are comorbidities. These comorbidities are managed by primary care physicians. Make sure you have that discussion. That's the end of it. Going beyond that and saying, well, let's follow up with it. Like we don't, we've got enough to do. I don't want to follow somebody's hemoglobin A1C. I don't want to follow their BMI. I'm a lot of time. Mary Cara docks are just lolly gagging around at the beach all the time. I think your bad mouthing, these are our listeners. Ship is going to plummet now after this. Right. I guess Kim, I have a question though. Like if they're so that. So actually going back to something that you said, the studies that in, I think it was psoriasis do some of them say that the, the benefits of it are independent of weight loss. I, I'd have to pull up the exact study on my laptop, but they, there's like always a line in there. So I guess would you be okay like, you know, a 30 year old HS female, otherwise healthy other than her HS just has obesity? No, not a brittle diabetic. I can believe you understand I would not touch the true diabetics. But would you okay in the sense of like again, going back to I think the full theme of the show, is it just helping the obesity, which is indirectly helping the HS? But again, HS, we still don't have great treatments. We have treatments, but you know, we still need more. So would you be okay then give it prescribically or no, even then in those cases, you'd be like, go back to your perfect. Yeah. So if, if they showed the data and actually did a study where they said, look, with these GLP one inhibitors in HS, for instance, they have shown it doesn't affect weight loss, doesn't affect type two diabetes. It is FDA approved to treat HS because we see these benefits. I'm fine with that because I can man, like I can manage a test. And that's how I'm going to be clinically following the patient. I think when you get into, you're on this drug for weight loss, there's a whole other way to manage weight loss that I think as Durham, I've never really done that. And I'm not going to start, you know, what about the cost effectiveness of it, Pat? And this is orders of magnitude more cost effective than any other drug we have for HS. I mean, but is it is it effective effective? Right. That's that's if they, if they really showed if there was, you know, it's, it's a fascinating thing of doing that clinical trial of, you know, monotherapy or maybe you put them on, yeah, just monotherapy with the GLP one for a yes. Like it would be like so cost effective. I haven't had any, like I haven't had that conversation with any of the HS patients, you know, they've never said to me, hey, there's these new drugs that cause weight loss. And I've been struggling with my weight. And I think that'll help HS because of certain things, you know, guide me through that process, help me there. That conversation hasn't come up. If they're talking about the GLP, the GIP combination. It's because they've already been discussing that with their PCP. That's not been a conversation that I've instigated. Will I start doing that? I don't know. Yeah, I don't know. Okay. All right. Well, Dr. Chenuele, I didn't, I don't think I warned you. We always close our episodes with a little trivia section here. It'll be vaguely related in some way to what we've been talking about. Okay. As long as it's not sports. I can't do any eye. I can't be done. No, no, no. Here's. So it now here's the only road you got. You got to let Pat and finish reading the question before. But as soon as he's done reading the question, the first person to shout out the answer gets the point. All right. These are people who may have benefited from the use of GLP wants. All right. Fiction only non fictional. I'm going to make this anything personal. Matt, you already benefited. So we've already had that discussion. Let's go back to the conversation you guys were having before I came on. A little bit. This second question. I think, well, we'll see. All right. I'm ready. This man was believed to have been over 300 pounds at the time of his death. He was survived by his sixth wife, Catherine Parr. Babe Ruth. No. Marlon Brandt. Historical. One of the Russians are. No, it's an overseas country, though. Who famously had six wives? Yeah, I know. Yeah, that's it. Henry. Okay. Oh, I got it. It was only like 18 clues. I was going to guess there was one of the old one of the original one of the emperors of the Holy Roman Empire after Charlemagne. There was a Charles the bald and a Charles the fat. Oh, yeah. I thought you made it on Charles the fat. I don't know how many wives he had. I should have known from the famous musical six. That should have. Yeah. If you read about Henry the eighth as he did get older, he was a mess. He probably had like horrible stasis ulcers. And he needed like mechanical things to like lift him on his horse and just get around. It was it was brutal. Poor who? All right. Who is the title character of the animated series that ran from 1972 to 1985 starring the junkyard gang with members like Russell, Mushemouth Rudy and weird Harold. Albert Albert. This was the one where I'm like, there's no way. This was before you were born. Probably. You've never heard of fat Albert. Oh gosh. I love you believe me. Hey. Hey. Yeah. This is where the generational divide. Family matters is probably like family matter. Oh yeah. No, this was yeah. We grew up with fat Albert. You couldn't have a show called fat anybody now, but this was the stuff of our child. That was like, he was wise. He was wise. He was. He all looked up to. Yeah. All the gang looked up to him. He was their leader. Yeah. All right. Which US president who served from 1909 to 1913 is widely considered to be the most overweight president. Garfield. No. Years after that. I don't know. Tell you Rose about. No. It was William Howard. Yeah. He's from Ohio. He was even the president. Yeah. You should have known that. Oh, hi. I should have known. Yeah. You know, interesting thing about William Howard Taft. There's probably this apocryphal story about how he got stuck in a white house bathtub. And so he had to get a special one brought in. That's probably not true. But did you know he went on to serve as the chief justice of the Supreme Court after his presidency? I forgot he was even president. So I certainly didn't have poor guy president thousands and beyond. No. This is this is why when you have a trivia team, you need people of many different generations. Yeah. You know what? So the whole overweight issue is is cut. It can be difficult to talk about. And I didn't want to bring up anybody who like was a lot. So I had to pick like dead people or made up people. Okay. So yeah, sorry about that. I'll write through three new ones with more modern take. I'll email it to you. Yeah. All right. Well, I would, Dr. Narlay, I want to thank you for joining us this week. This was a really fun and interesting discussion. And I want to thank all of our listeners for joining us. I hope you learned a few things. I hope you laughed once or twice, but mostly I'm hoping to plan to join us next week. And until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are Derms on Drugs.