Latest / The Science of Skin / GLP-1s in Dermatology: Tirzepatide, Semaglutide & Retatrutide for Psoriasis & Metabolic Skin Disease

Transcript

GLP-1s in Dermatology: Tirzepatide, Semaglutide & Retatrutide for Psoriasis & Metabolic Skin Disease · The Science of Skin

• 0:08
  SPEAKER_01: Hello and welcome to the Science of Skin Podcast.
• 0:10
  SPEAKER_01: My name is Dr.
• 0:11
  SPEAKER_01: Ted Lane.
• 0:11
  SPEAKER_01: I'm a board certified dermatologist in Austin, Texas.
• 0:15
  SPEAKER_01: And with me today, I'm very excited, is uh a new friend, Dr.
• 0:20
  SPEAKER_01: Lindsay Bordone.
• 0:21
  SPEAKER_01: Lindsay, how are you?
• 0:22
  SPEAKER_00: I'm great.
• 0:23
  SPEAKER_00: Thanks for having me.
• 0:24
  SPEAKER_00: This is really exciting.
• 0:25
  SPEAKER_01: Yeah, for me as well.
• 0:26
  SPEAKER_01: So Lindsay and I met recently at the AAD, and she specializes in metabolic disease affecting the skin.
• 0:34
  SPEAKER_01: And like my antenna went up automatically, and like I wouldn't let her leave until I like chattered her ears off.
• 0:40
  SPEAKER_01: Poor thing.
• 0:41
  SPEAKER_01: I'm surprised she still accepted my uh invitation to join the podcast.
• 0:45
  SPEAKER_01: But Lindsay is uh she was for 12 years at Columbia on staff at the Columbia uh medical school as uh what associate professor of dermatology.
• 0:54
  SPEAKER_01: Is that right, Lindsay?
• 0:55
  SPEAKER_01: Yes.
• 0:55
  SPEAKER_01: Yeah.
• 0:56
  SPEAKER_01: And she specialized in inflammatory hair loss conditions, then kind of transitioned to metabolic diseases affecting the skin, and was super, super busy, decided to make a bit of a change and now is in Scottsdale.
• 1:09
  SPEAKER_01: And is uh a dermatologist at your own practice, Bordeaux dermatology, right?
• 1:13
  SPEAKER_01: But soon to join the Arizona University of Arizona faculty.
• 1:17
  SPEAKER_01: Uh and so they are very, very lucky.
• 1:19
  SPEAKER_01: So, Lindsay, um, first of all, thank you for being here.
• 1:23
  SPEAKER_01: Um, and I think a lot of derms have thought about GLP1 agonists, maybe considered prescribing them.
• 1:31
  SPEAKER_01: We've seen some of the data that's come out with the trzepatide plus uh ixakisumab for um psoriasis.
• 1:38
  SPEAKER_01: But you really have been one of the first kind of prescribers of GLP1s in our specialty.
• 1:44
  SPEAKER_01: Kind of talk about why you thought GLP1 agonists deserve to be used by a dermatologist and how they benefit your patients.
• 1:53
  SPEAKER_00: So, one of the things that I first noticed was my psoriasis patients, as their BMI went up, there's a lot of data showing that once your BMI is over 35, biologics just don't work as well.
• 2:05
  SPEAKER_00: And I remember when I was in residency going to different talks at the AAD, and people were talking about combining different immunosuppressives and patients who were resistant to therapy and had a very high BMI.
• 2:17
  SPEAKER_00: And it just seemed like this BMI was part of the disease process, but there was nothing really for it at the time.
• 2:24
  SPEAKER_00: Fast forward when GLP1s came out, I thought, oh my God, this seems like the missing piece that we've needed for a long time.
• 2:32
  SPEAKER_00: So I decided to start looking into treating patients with these medications because we have a lot of information showing that fat is basically like an organ and produces tons of inflammation.
• 2:44
  SPEAKER_00: And when you have one of these inflammatory conditions, if you're making more and more inflammation, there's only so much that a medication can do to counteract that.
• 2:53
  SPEAKER_00: So I started checking uh different levels of metabolic markers in people's uh on their blood test.
• 3:01
  SPEAKER_00: And what was interesting is we found something unexpected.
• 3:05
  SPEAKER_00: Um, their sugars were often fine, but if they had a very high insulin to make their sugars fine, that was abnormal.
• 3:13
  SPEAKER_00: But no one was ever checking insulin.
• 3:16
  SPEAKER_00: So that's where we started moving further with checking these metabolic markers.
• 3:20
  SPEAKER_00: And what we found is many people with inflammation have very high insulin levels, not sugar, but high insulin.
• 3:27
  SPEAKER_01: So is there a correlation there for it?
• 3:29
  SPEAKER_01: Like if we checked for hyperinsulinemia and elevated CRP or ESR other inflammatory markers, Lindsay, would we see a correlation there?
• 3:36
  SPEAKER_01: Or would uh the insulin levels maybe precede an elevation in the other inflammatory markers that we're used to?
• 3:43
  SPEAKER_00: Um, well, it's a it depends on when the disease started.
• 3:46
  SPEAKER_00: There are people who baseline are going to have psoriasis and their metabolic disease or adiposity or obesity will make it worse.
• 3:54
  SPEAKER_00: And then there are people that are prone to these conditions, but something needs to push them over a threshold before they actually start developing the condition.
• 4:03
  SPEAKER_00: So it can go either way, though I have seen patients that I think they probably develop metabolic disease first, but I have no way of going back and knowing that.
• 4:13
  SPEAKER_00: Regardless, the management improves when you put people on these meds.
• 4:16
  SPEAKER_00: So we haven't gotten um to the point where we're doing these deep dives and testing people who just have a family history of psoriasis, for instance.
• 4:25
  SPEAKER_00: Um, but most likely we would see that there's some metabolic disease contributing from the start.
• 4:30
  SPEAKER_01: Okay.
• 4:31
  SPEAKER_01: And just logistically, Lindsay, since many of us don't test for insulin, is there a time of day kind of like cortisol when you should check for insulin?
• 4:38
  SPEAKER_00: Absolutely.
• 4:39
  SPEAKER_00: So the one of the challenges I've had is that patients will come to me and they'll say, Oh, I I have my insulin check because someone heard about it on the internet.
• 4:48
  SPEAKER_00: It has to be done at a specific time of day.
• 4:50
  SPEAKER_00: You want it to be fasting between eight and nine in the morning because later on your circadian rhythm lowers your insulin.
• 4:57
  SPEAKER_00: And in the morning, you get a good snapshot of what it's like after you haven't been eating.
• 5:03
  SPEAKER_00: So your insulin should be low.
• 5:04
  SPEAKER_00: And if it's high when you're fasting, that's abnormal.
• 5:07
  SPEAKER_01: Okay.
• 5:08
  SPEAKER_01: So uh you you see a patient high BMI, perhaps.
• 5:12
  SPEAKER_01: Um, you check insulin based on, you know, between eight and nine in a fasting state, it's elevated.
• 5:18
  SPEAKER_01: You see them, they're they're developing this moderate to severe psoriasis, perhaps, and you're thinking, okay, I'm kind of behind the eight ball here, right?
• 5:26
  SPEAKER_01: Because I could start them on a biologic um or a small peptide or something like that.
• 5:32
  SPEAKER_01: And you know, I probably will get some good results, but because of their obesity and the fact that that adipose tissue is acting as a source of inflammatory cytokines, inflammation in the body, um, I'm not I really need to uh target the that source of inflammation.
• 5:49
  SPEAKER_01: So which one do you pick?
• 5:51
  SPEAKER_01: Do you do you go with uh semaglutide or do you think you go straight to terzepatide?
• 5:57
  SPEAKER_00: Well, in the modern medical world, I think a lot of times we default to whatever the insurance will cover.
• 6:03
  SPEAKER_00: My preferred medication is terzepatide for various reasons, um, because it has additional GIP, it's good for your bones, tends to have less side effects.
• 6:12
  SPEAKER_00: But basically it comes down to what insurance will cover.
• 6:15
  SPEAKER_01: Yeah.
• 6:16
  SPEAKER_01: So assuming that terzeptide, we could get it, right?
• 6:18
  SPEAKER_01: Either through cash pay or we actually get it covered through obesity, for example.
• 6:22
  SPEAKER_01: Um, so many benefits.
• 6:24
  SPEAKER_01: I mean, you just kind of covered them very quickly, but there's so many additional benefits for terzepatide.
• 6:30
  SPEAKER_01: First of all, can we just talk about how it works as a GLP1 agonist?
• 6:34
  SPEAKER_01: Uh Lindsay, I I heard recently that most of us kind of have this false idea that we think it works by delaying gastric emptying and therefore kind of giving us this full false sense of satiety, maybe not false, but the sense of satiety.
• 6:47
  SPEAKER_01: But it there's actually more central mechanisms of actions in terms of at the brain level, which is how it works.
• 6:53
  SPEAKER_01: Is that is that true?
• 6:55
  SPEAKER_00: Yeah, so it works.
• 6:57
  SPEAKER_00: There's receptors for GLP1 in the brain, the pancreas, the gut.
• 7:00
  SPEAKER_00: There there seems to there's GLP1 receptors in the testes.
• 7:04
  SPEAKER_00: Um so there's uh a wide number of organs that this medication, this peptide binds to, and it's not just delaying gastric emptying.
• 7:15
  SPEAKER_00: Even without weight loss, people have improvement in things like cardiovascular disease because it binds to receptors along the endothelium, uh, similar to insulin.
• 7:24
  SPEAKER_00: So these drugs are like I think they're gonna be like the advent of penicillins, where there was a time in my career before GLP once, and there will be a time after.
• 7:36
  SPEAKER_00: And probably my career is gonna be marked by that um more than any other drug or drug class.
• 7:44
  SPEAKER_01: Yeah.
• 7:45
  SPEAKER_01: It's so I I just think this kind of um the way you're thinking about metabolic disease and how it kind of affects the skin.
• 7:55
  SPEAKER_01: And uh, you know, we were just having a conversation that metabolic disease may uh affect the skin and be the first place that we actually find the the signs of metabolic disease is in the skin as well.
• 8:07
  SPEAKER_01: And that's really important because we know that with untreated metabolic disease shortens lifespan.
• 8:12
  SPEAKER_00: Yeah.
• 8:12
  SPEAKER_01: So can you talk about that?
• 8:14
  SPEAKER_01: Just um how metabolic disease affects the skin?
• 8:16
  SPEAKER_01: I mean, we obviously through increased insulin you talked about is a way to to kind of look for it, but in terms of how it's affecting the skin.
• 8:24
  SPEAKER_00: So I think people think of like your liver or your kidneys or your heart as the organs that get damaged by metabolic disease.
• 8:32
  SPEAKER_00: The heart is, I mean, the skin is just as susceptible and we can see it.
• 8:36
  SPEAKER_00: And typically what insulin should do when you're sensitive to it is you have these like blood vessels and there are insulin receptors along the blood vessel wall that insulin binds to.
• 8:47
  SPEAKER_00: So the blood vessel opens, the blood rushes through, cells pick out the sugar and the sugar comes down.
• 8:52
  SPEAKER_00: But when your insulin's always high, it's like your mom always screaming at you.
• 8:55
  SPEAKER_00: You stop listening.
• 8:56
  SPEAKER_00: And those blood vessels don't open in response to insulin, and you need more and more of it to compensate.
• 9:03
  SPEAKER_00: So this there's this compensatory hyperinsulinemia.
• 9:06
  SPEAKER_00: So your insulin gets very high, and it's like a muscle that you keep flexing, like your pancreatic cells that make insulin, the beta-islet cells, they start to hypertrophy.
• 9:16
  SPEAKER_00: They get larger, they become more productive, but then they start producing insulin all the time.
• 9:20
  SPEAKER_00: And it's this faulty feedback loop where in periods of famine, it might be beneficial to have a lot of insulin to store food as fat and then get hungry again quickly.
• 9:28
  SPEAKER_00: But now that we don't need it, the problem is you can have a crash of sugar and people can get really like tired after meals.
• 9:36
  SPEAKER_00: That's an early sign of insulin resistance.
• 9:39
  SPEAKER_00: And um you can have a lot of inflammation from that insulin as well.
• 9:44
  SPEAKER_00: But there are all these downstream effects of chronically high insulin that we see in the skin because um we can actually see blood flow in the skin, for instance.
• 9:55
  SPEAKER_00: Like if you look at the hair on someone's forearms, once someone starts developing insulin resistance, they'll start to have loss of hair along their forearms.
• 10:04
  SPEAKER_00: It's because of the chronic vasoconstriction as a result of chronically high insulin.
• 10:09
  SPEAKER_00: So there's other things like we'll see thickening of skin on the back of the neck or skin tags because co-localized with insulin receptors are um insulin-like growth factor receptors, and insulin itself weakly binds to that.
• 10:25
  SPEAKER_00: So it starts to have the effect of growth factor and your skin starts thickening.
• 10:29
  SPEAKER_00: So we see these before other people do, and there's soft tissue growth internally, but we see it on the skin.
• 10:36
  SPEAKER_01: That is so interesting.
• 10:38
  SPEAKER_01: Okay.
• 10:39
  SPEAKER_01: So we've kind of convinced hopefully our audience of the benefits of terzepatite in particular.
• 10:44
  SPEAKER_01: Um, you know, we there's a new one that's gathering a lot of media attention, Lindsay, the med retitrutide.
• 10:51
  SPEAKER_00: Yeah.
• 10:51
  SPEAKER_01: Uh can you talk to us a little bit about that?
• 10:53
  SPEAKER_01: Maybe give us um some insider info on retitrutide.
• 10:58
  SPEAKER_00: So I am beyond excited about that medication, but for the right person.
• 11:03
  SPEAKER_00: So there's semaglitide, which is GLP1, and then there's terzepitide, which is GLP1 plus GIP, and then retitrutide is like the cute name for it is like triple G, because it's GLP1, GIP plus uh glucagon.
• 11:16
  SPEAKER_00: And glucagon um helps with with use of fat so that you don't store it as much.
• 11:23
  SPEAKER_00: And the miraculous thing about retitrutide is its effect on fatty liver.
• 11:28
  SPEAKER_00: So the WHO estimated that by 2030, the number one cause for like liver issues in the world was gonna be fatty liver.
• 11:35
  SPEAKER_00: And now they're gonna have to totally re-uh rethink their um algorithm because we're actually gonna see um liver transplants as a result of fatty liver and liver cirrhosis from fatty liver drop dramatically.
• 11:49
  SPEAKER_00: I think the hope was that in the clinical trial, like 30 or 50% of people may have seen some degree of improvement, but actually at the higher dose of retitrutide, 93% had complete clearance of their fatty liver.
• 12:03
  SPEAKER_00: Like that's unheard of compared to 4.6% of the placebo.
• 12:08
  SPEAKER_00: So, I mean, the amount of liver disease, the single most costly medical event is a liver transplant.
• 12:16
  SPEAKER_00: Um, it costs a lot of money leading up to the liver transplant, all the care after, uh, the actual surgery is a fortune.
• 12:22
  SPEAKER_00: And I think we're gonna see those types of medical costs go down.
• 12:26
  SPEAKER_00: So we know that there's liver that accumulates, I mean, there's fat that accumulates in the liver.
• 12:32
  SPEAKER_00: The other thing I want people to wrap their heads around is this steatosis that happens, which is the infiltration of muscle or any regular tissue with fat.
• 12:43
  SPEAKER_00: So there's something called myosteatosis, which occurs when people gain a lot of weight.
• 12:47
  SPEAKER_00: They don't just get fatty liver, they get fatty muscle, fatty cardiac tissue, fatty pancreas.
• 12:53
  SPEAKER_01: And that's I never thought about that actually.
• 12:55
  SPEAKER_01: Yeah.
• 12:55
  SPEAKER_00: Yeah.
• 12:55
  SPEAKER_00: So your pancreas actually becomes less useful as you become more insulin resistant because it becomes less functional because of all of the fat that's deposited within.
• 13:05
  SPEAKER_00: So um, yeah, I mean, retotrutite is gonna change medicine generally, and we're gonna see a heck of a lot less fatty liver.
• 13:14
  SPEAKER_00: But the thing that's now been spoken about is these drugs are getting to the point where they're almost too good.
• 13:21
  SPEAKER_00: Retitrutide is so effective at weight loss that I think it's gonna be used as part of step therapy rather than first line therapy because you could inadvertently cause too much weight loss too quickly in someone who's very sensitive to it if they've never tried another medication in this drug class.
• 13:37
  SPEAKER_01: Got it.
• 13:37
  SPEAKER_01: Yeah, I mean, I was reading some of the data for retitrutide.
• 13:40
  SPEAKER_01: People were losing 30% of their body weight.
• 13:43
  SPEAKER_01: And some people were dropping out because they were nervous about all the weight loss they were losing.
• 13:47
  SPEAKER_01: Oh, yeah.
• 13:48
  SPEAKER_01: To your point, it was working too well and making people a bit alarmed.
• 13:53
  SPEAKER_01: Terzepatide helps with outdy liver as well, though, right, Lindsay?
• 13:56
  SPEAKER_01: Doesn't it?
• 13:56
  SPEAKER_01: Um there's data.
• 13:57
  SPEAKER_00: It absolutely does.
• 13:58
  SPEAKER_00: And and trzepatite is a little bit better for bones, too.
• 14:01
  SPEAKER_00: It's better for bone remodeling.
• 14:03
  SPEAKER_00: So if I have someone with a history of osteopenia, I prefer that over um semaglutide for sure.
• 14:08
  SPEAKER_01: Okay, that's interesting.
• 14:09
  SPEAKER_01: Is are there any other um uh characteristics of trzepatide um that would make you choose that drug over semaglutide or and or retotrutide?
• 14:20
  SPEAKER_00: Um, just the decrease in symptoms.
• 14:23
  SPEAKER_00: Patients seem to have like better tolerance of the medication.
• 14:27
  SPEAKER_01: Okay.
• 14:28
  SPEAKER_01: Now, can we talk about sarcopenia?
• 14:30
  SPEAKER_01: Um the idea of muscle loss, because that I I oh yeah, such a big deal um for everyone that they're so worried.
• 14:38
  SPEAKER_01: They don't ever go to the gym, but they're worried about losing muscle, right?
• 14:40
  SPEAKER_01: So um it's just I just don't understand that.
• 14:44
  SPEAKER_01: But uh if you could talk to us about like why we think sarcopenia occurs and how do we combat that, and does reditrutide have uh that side effect of sarcopenia um or not?
• 14:55
  SPEAKER_00: So I actually have a ton of thoughts on this.
• 14:57
  SPEAKER_00: Um first of all, the way that the uh the studies were done to look for loss of muscle mass was through DEXA scans.
• 15:05
  SPEAKER_00: And DEXA scans will look at volume, but they won't really look like an MRI would at the composition of muscle.
• 15:12
  SPEAKER_00: And MRIs would be extremely expensive and time consuming.
• 15:15
  SPEAKER_00: So DEXA scans are the standard.
• 15:18
  SPEAKER_00: So we don't know how much of this was myosteatosis, like fat in the muscle that went away, and how much of it was actually lean muscle loss.
• 15:29
  SPEAKER_00: And I think another study that might be useful, which I I don't have the capacity to do, is some sort of resistance metrics where someone shows their strength level through different exercises ahead of starting therapy and then throughout therapy to see if their strength actually changes, because I really question whether or not this is true muscle loss or if it's just loss of myosteatosis.
• 15:55
  SPEAKER_00: And then the other thing is there's um loss of hunger, but it's not a selective loss of hunger.
• 16:01
  SPEAKER_00: There is a decrease in the amount of food that people want to take in generally.
• 16:05
  SPEAKER_00: And I think if someone's not counseled very well on taking in enough protein, then you can start to have muscle loss.
• 16:12
  SPEAKER_00: So I think there's two factors here that we haven't really teased out.
• 16:16
  SPEAKER_00: People are much more informed now about getting enough protein.
• 16:19
  SPEAKER_00: And I think we've gotten the message out that while they're on these medications, they really should be doing resistance training because it's good for you anyway.
• 16:26
  SPEAKER_00: And muscle accounts for about 80% of glucose use, and it's the body's uh only currency to deal with glucose without medication.
• 16:34
  SPEAKER_00: But I I wonder how much of this muscle loss is true muscle loss versus a decrease in the volume.
• 16:42
  SPEAKER_00: And with that said, retotrutide is a much more powerful medication.
• 16:47
  SPEAKER_00: So if there is muscle loss, I would anticipate that it would be more significant with retitrutide with weight loss.
• 16:54
  SPEAKER_01: Yeah, I was it's it's confusing, right?
• 16:56
  SPEAKER_01: Because you hear of drugs that are in development that that say, and we spare the sarcopenia, right?
• 17:01
  SPEAKER_01: But we don't understand the cause of the sarcopenia.
• 17:04
  SPEAKER_01: So I don't I don't understand how they can make that claim.
• 17:07
  SPEAKER_01: Do you have any insight on that?
• 17:09
  SPEAKER_00: I think that there needs to be more research in this area because I just don't there isn't tons of great data.
• 17:16
  SPEAKER_00: They have like the standards that they used for the clinical trial, but I think there is some components missing there to um give us more detail on like muscle composition and actual strength.
• 17:28
  SPEAKER_01: You know, the the idea that the fat in the muscle, the myosteatosis, is that fat that's in the muscle, is it as estrogenic, for example?
• 17:37
  SPEAKER_01: Is it as inflammatory as any fat that we find?
• 17:40
  SPEAKER_01: Uh any brown fat?
• 17:42
  SPEAKER_00: Visceral fat is the worst.
• 17:44
  SPEAKER_00: It produces tons of interleukin 6.
• 17:46
  SPEAKER_00: Subcutaneous fat produces more interleukin-17.
• 17:49
  SPEAKER_00: Um but I'm not sure about muscle fat.
• 17:53
  SPEAKER_00: There's not as much as much research on that for sure.
• 17:57
  SPEAKER_01: It would be much much more difficult to research, I'd imagine.
• 17:59
  SPEAKER_01: Okay.
• 18:00
  SPEAKER_01: Yeah.
• 18:00
  SPEAKER_01: Um, okay, so you're a dermatologist who's never prescribed trusepatite or semaglutide before, and you're thinking, okay, here's an obese um high BMI psoriasis patient.
• 18:12
  SPEAKER_01: I really want to try it.
• 18:14
  SPEAKER_01: I can see that the starting dose is 2.5 once a week.
• 18:18
  SPEAKER_01: You know, do I need to check labs?
• 18:20
  SPEAKER_01: Do I, is there anything I should check before I get started or I should follow up on after a month?
• 18:26
  SPEAKER_01: Is there anything that you would recommend in terms of kind of enveloping the start of terzepatide with good medical care?
• 18:34
  SPEAKER_00: There so there's no standard of labs that need to be checked while on these medications.
• 18:39
  SPEAKER_00: That being said, I think for insurance purposes, it's good to have some sort of baseline labs.
• 18:44
  SPEAKER_00: I do like to check a HOMA IR score where I check fasting insulin and fasting glucose to see how insulin resistant someone is.
• 18:51
  SPEAKER_00: Okay.
• 18:51
  SPEAKER_00: I'll also check an A1C.
• 18:53
  SPEAKER_00: And then the other thing I always uh put in with my labs are a lipid panel because I want to see if someone's triglycerides are up.
• 19:00
  SPEAKER_00: There's something called selective insulin resistance where you can be resistant to it in your liver, but sensitive to it in your muscle, which helps with your sugars looking fine.
• 19:08
  SPEAKER_00: But then what happens is triglycerides go up, HDL goes down, LDL goes up, and then there's inversion of the liver enzymes.
• 19:15
  SPEAKER_00: So instead of your ALT being lower than your AST, you'll start to see them flip.
• 19:20
  SPEAKER_00: And then ALT will be like double, even if it's in range, you start to notice these trends.
• 19:25
  SPEAKER_00: So I like to have that as a marker so I could A, show patients the improvements that they're gaining from these medications, but also so I have some ammunition in the future.
• 19:35
  SPEAKER_00: If a patient ever needs to get reapproved for the medication or changes insurance and their new insurance doesn't want to cover them because their BMI wasn't over 35 or whatever that insurance decides is their standard.
• 19:47
  SPEAKER_00: Okay.
• 19:48
  SPEAKER_01: Gotcha.
• 19:48
  SPEAKER_01: Okay.
• 19:49
  SPEAKER_01: So you get some baseline lab work.
• 19:51
  SPEAKER_01: That's some labs that we can follow over time, like you said, for ammunition for the payers.
• 19:55
  SPEAKER_01: I totally get that.
• 19:56
  SPEAKER_01: And then uh after what what is your thought and what is your algorithm for escalating the dose?
• 20:02
  SPEAKER_00: So it depends.
• 20:03
  SPEAKER_00: Um, in the when these drugs first came out, the standard was escalate every single month to the point of tolerance.
• 20:09
  SPEAKER_00: I I definitely don't do that because you don't want people losing weight too quickly.
• 20:13
  SPEAKER_00: They'll develop gallstones, they'll get a telogen a fluvium.
• 20:16
  SPEAKER_00: So instead, you pace them at one to two pounds a week max.
• 20:20
  SPEAKER_00: Okay.
• 20:20
  SPEAKER_00: And I usually don't move up the dose unless I plateaued for at least three weeks.
• 20:25
  SPEAKER_00: Because if you keep escalating, that weight loss can snowball so quickly.
• 20:30
  SPEAKER_00: And um it it starts to cause problems after.
• 20:34
  SPEAKER_00: So I would say just base it on one to two pounds a week.
• 20:37
  SPEAKER_01: Okay.
• 20:38
  SPEAKER_01: And do you escalate per kind of the label where it goes from 2.5 to 5, or will you ever jump up to 7.5?
• 20:44
  SPEAKER_01: What are your thoughts on that?
• 20:45
  SPEAKER_00: I I only go up uh based on the standard dosing because I I've had patients who I'm I don't know where they were getting the medications.
• 20:54
  SPEAKER_00: They've had these big jumps.
• 20:55
  SPEAKER_00: And I actually had one patient who wound up in the hospital.
• 20:59
  SPEAKER_00: Um, I think they this is before they had the self-pay option, and they got gastroparesis because it was just too much of a shock.
• 21:06
  SPEAKER_00: I know.
• 21:07
  SPEAKER_01: Yeah.
• 21:09
  SPEAKER_01: Well, talking about the gut though, right?
• 21:12
  SPEAKER_01: But most of the side effects that happen, most of the adverse events are related to the GI tract.
• 21:17
  SPEAKER_01: Um and a lot of people experience constipation, certainly nausea.
• 21:21
  SPEAKER_01: Do you have any tips or pearl to help with those kind of adverse events?
• 21:26
  SPEAKER_00: Yeah, so I have patients, I tell them never eat at night because if it's delaying gastric emptying and then you're laying down, like that is not gonna help with your nausea.
• 21:35
  SPEAKER_00: Um, it's also good to have a fast overnight so your insulin comes down.
• 21:38
  SPEAKER_00: So I caution people on that and eating high fiber foods at dinner.
• 21:42
  SPEAKER_00: If they're gonna have high fiber foods, I tell them to do it earlier in the day because that also can delay gastric emptying a little bit.
• 21:50
  SPEAKER_00: Um, and then many people will drink water when they eat, but they don't think of drinking water like between between meals or between snacks.
• 21:59
  SPEAKER_00: And since they're Not snacking anymore, they get dehydrated.
• 22:01
  SPEAKER_00: So I tell them take psyllium husk or some sort of fiber gummy, drink a lot of water.
• 22:06
  SPEAKER_00: And usually that's about enough to get things under control.
• 22:09
  SPEAKER_00: If not, I have them take a little bit of magnesium.
• 22:11
  SPEAKER_01: Magnesium.
• 22:12
  SPEAKER_01: Okay.
• 22:13
  SPEAKER_01: This idea of B6 to help with nausea, has that ever worked for you?
• 22:17
  SPEAKER_00: I haven't found it to be useful.
• 22:19
  SPEAKER_00: I wish it was.
• 22:20
  SPEAKER_01: Yeah.
• 22:21
  SPEAKER_01: Okay.
• 22:22
  SPEAKER_01: And then a lot of times you'll find compounding pharmacies compound it with B12 for vitality, I guess.
• 22:29
  SPEAKER_01: I don't know if that's metformin.
• 22:31
  SPEAKER_00: We do know that over time, the one side effect of metformin is B12 can get low.
• 22:36
  SPEAKER_00: Okay.
• 22:36
  SPEAKER_00: Um, they probably are just thinking in the same like realm of metabolic meds that maybe B12 would be helpful so it doesn't get low.
• 22:43
  SPEAKER_01: But okay.
• 22:44
  SPEAKER_01: All right.
• 22:45
  SPEAKER_01: And so now I want to ask you, we didn't discuss this, Lindsay, so I'm kind of giving you a left field kind of question, but the idea of using peptides along with GLP ones, right?
• 22:55
  SPEAKER_01: GLP ones are peptides, but adding in some of these peptides that are not well studied, but certainly extremely popular, uh, a lot of them are secretagogs for human growth factor human growth factor.
• 23:07
  SPEAKER_01: So semorin or tesamorin.
• 23:09
  SPEAKER_01: Um, any thoughts on adding that in with your GLP ones?
• 23:13
  SPEAKER_01: And have you ever done it?
• 23:15
  SPEAKER_00: No, I've actually never ordered peptides.
• 23:18
  SPEAKER_00: I get nervous about things that don't have a a lot of data.
• 23:22
  SPEAKER_00: Um I don't know.
• 23:23
  SPEAKER_00: I and then even with other meds like that are FDA approved, like starting an estrogen patch, for instance, there's certain um outcomes that you would expect with estrogen and certain outcomes that you would expect with a GLP one and side effects with one or the other, and they can um overlap in some ways, and estrogen can augment the effects of a GLP one.
• 23:45
  SPEAKER_00: They've done studies showing that if one plus one doesn't equal two, they they actually have like a synergistic amplified effect.
• 23:53
  SPEAKER_00: So I tell people if you're gonna start one, do one and then wait a couple months and then start another so we know what's doing what and we don't start to try to figure it out after the fact.
• 24:02
  SPEAKER_00: Um, because especially with the GI side effects and um with other issues, like for instance, with estrogen, your blood pressure can improve a little bit.
• 24:11
  SPEAKER_00: So so can they because of the GLP1's effect on the endothelium?
• 24:15
  SPEAKER_00: So if someone starts getting hypotensive and their blood pressure gets low, it's like which one do you stop?
• 24:21
  SPEAKER_01: Yeah.
• 24:22
  SPEAKER_01: I hadn't heard that before that there's a synergy between estrogen and the trasepatide.
• 24:28
  SPEAKER_01: That's really interesting.
• 24:28
  SPEAKER_01: So certainly not something that I think a derm would want to kind of manage uh in terms of estrogen patches, but good to know uh that if you are going to start a drug like that and they're on an estrogen patch, note that you may get a kind of a turbo boost of the effect.
• 24:44
  SPEAKER_01: Any other hormone like testosterone, would that do the same thing?
• 24:48
  SPEAKER_00: Or no, testosterone, well, testosterone is good uh somewhat metabolically, but the data on testosterone hasn't been as encouraging as estrogen.
• 24:57
  SPEAKER_00: Um estrogen has been shown to be significantly beneficial.
• 25:01
  SPEAKER_00: Now the um Menopause Society as of 2022 recommends all women under the age of 60 and within 10 years of menopause be on estrogen.
• 25:09
  SPEAKER_00: And the the results with testosterone, I think people would were hoping it would have a bigger health impact because I think it makes people feel good, but actually it it's been a bit disappointing.
• 25:20
  SPEAKER_01: Okay.
• 25:21
  SPEAKER_01: Uh anything that we that you commonly add to the trzepatide for either enhancing benefits, decreasing uh side effects.
• 25:30
  SPEAKER_01: I know we talked about psilium and increasing water intake, any other vitamin that you would recommend, or do you recommend taking vitamins with it?
• 25:37
  SPEAKER_00: Yeah, because people um, if they go through periods of nausea and they're missing some micronutrients, I just have them take a multivitamin.
• 25:44
  SPEAKER_00: Um, other than that, I usually counsel on good exercise, getting good sleep.
• 25:50
  SPEAKER_00: Um, if they want to do something that augments it and they're in perimenopause, I say absolutely go and consider hormone therapy just for the other health benefits as well.
• 26:01
  SPEAKER_01: Yeah, yeah.
• 26:01
  SPEAKER_01: And in terms of um protein intake, Lindsay, uh, do you recommend, you know, we've heard a lot of this um, you know, one one gram per weight, body weight pound, uh, ideal body weight pound.
• 26:14
  SPEAKER_01: Is that something that you are aligned with?
• 26:17
  SPEAKER_00: Well, when you're losing weight, you actually want to get a little bit more.
• 26:20
  SPEAKER_00: You want 1.2 to 1.6 uh grams per ideal body weight kilogram.
• 26:25
  SPEAKER_00: Kilogram.
• 26:26
  SPEAKER_00: Okay.
• 26:26
  SPEAKER_00: Yeah.
• 26:27
  SPEAKER_00: So I recommend a little bit more when someone's actively losing weight.
• 26:31
  SPEAKER_00: And then the other thing I was gonna say is you mentioned what do I add with these medications.
• 26:38
  SPEAKER_00: Actually, the bigger thing I've um encountered is subtracting drugs.
• 26:43
  SPEAKER_00: So if patients have high blood pressure, I have to monitor, have them get a home blood pressure cuff and take their blood pressure uh once a week because I I had one patient go off of four blood pressure meds while he was on trzepatide.
• 26:57
  SPEAKER_00: Um, and I've had other patients go off of medications that uh we were not anticipating they would go off of.
• 27:03
  SPEAKER_01: Okay.
• 27:04
  SPEAKER_01: I just want to circle back to the protein because I think we may have um confused.
• 27:07
  SPEAKER_01: Um I said something that may have been confusing because I said one gram per pound, ideal pound, and you were saying one point two to one point six ideal kilogram.
• 27:15
  SPEAKER_01: Uh, and so I've heard both, but you stick to the 1.2 to 1.6 of per kilogram, um, especially during the the kind of initial rapid weight loss phase.
• 27:24
  SPEAKER_00: Yeah, it's this that's what the standard is.
• 27:27
  SPEAKER_00: Um because if it were per pound, it would be significantly yeah more.
• 27:32
  SPEAKER_01: It would be much more.
• 27:33
  SPEAKER_01: Okay.
• 27:34
  SPEAKER_01: Okay, gotcha.
• 27:35
  SPEAKER_01: I I have to say something about the the hydration.
• 27:38
  SPEAKER_01: Um, I totally agree with you.
• 27:39
  SPEAKER_01: When you start losing your your kind of appetite, you lose your thirst as well.
• 27:45
  SPEAKER_01: And so it is a huge push for patients to continue with their hydration because otherwise they'll be consistently dehydrated, constantly dehydrated, which of course can affect the kidneys over time.
• 27:55
  SPEAKER_01: So it's it's really important to push hydration for these patients and make sure that you are um you know checking capillary refill.
• 28:02
  SPEAKER_01: I mean, there's just just ways to check um to see how they're doing with their water intake because it can be a major issue.
• 28:09
  SPEAKER_01: Um, Lindsay, thank you so much.
• 28:11
  SPEAKER_01: We're already at the end of our episode.
• 28:12
  SPEAKER_01: I'm I I told you I think we're gonna do two or three because you're so knowledgeable.
• 28:16
  SPEAKER_01: I love this so much.
• 28:17
  SPEAKER_01: Thank you.
• 28:17
  SPEAKER_00: No problem.
• 28:18
  SPEAKER_00: Thanks so much for having me.
• 28:19
  SPEAKER_00: This is great.
• 28:20
  SPEAKER_01: Yeah.
• 28:21
  SPEAKER_01: Oh, wow, this is great.
• 28:22
  SPEAKER_01: So uh I'm Dr.
• 28:23
  SPEAKER_01: Ted Lane, board certified dermatologist in Austin.
• 28:25
  SPEAKER_01: I'm your uh host for today for the Science to Skin podcast.
• 28:28
  SPEAKER_01: Of course, we've had the amazing Dr.
• 28:30
  SPEAKER_01: Lindsay Bordone in Scottsdale, Arizona on.
• 28:33
  SPEAKER_01: Lindsay has tons of published literature.
• 28:35
  SPEAKER_01: So if you just want to find out more of what she's done in her amazing career, B-O-R-D-O-N-E is how you spell her last name, and you can check it out.
• 28:43
  SPEAKER_01: Uh listen, if you enjoyed the episode, we have found that the word of mouth is the best way.
• 28:49
  SPEAKER_01: We've uh kind of spread the word about the Science of Skin podcast.
• 28:52
  SPEAKER_01: So if you've enjoyed it, please let your friends know, your colleagues.
• 28:54
  SPEAKER_01: Of course, give us a five-star rating and subscribe as well.
• 28:57
  SPEAKER_01: We would appreciate all the support we can get.
• 29:00
  SPEAKER_01: Uh for Lindsay Bordone out in Scottsdale, Arizona, I'm Dr.
• 29:03
  SPEAKER_01: Ted Lane.
• 29:04
  SPEAKER_01: Thank you so much for listening.