Speaker 1: Hello, this is the Itchy and Bitchy Podcast because being
Speaker 1: itchy is bitchy and our medical system sucks. I'm doctor
Speaker 1: Keith Milica, a vetnary, allergist and dermatologist.
Speaker 2: And I'm Stephen Miller, a doctor of nursing practice and
Speaker 2: a Q Care nurse practitioner.
Speaker 1: Send us your questions at ask at itch not dot com.
Speaker 1: We love you, but we're not your doctors. The information
Speaker 1: we discuss is not direct medical advice. Please talk to
Speaker 1: your provider who is the expert on your care. The
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Speaker 1: latest veterinary medical research. Visit docichi dot com or find
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Speaker 1: send us a question at a at itchno dot com. Thanks, hello,
Speaker 1: doctor Miller, how's it going.
Speaker 2: Hi? Welcome to all of our listeners. I'm so glad
Speaker 2: we're back together.
Speaker 1: Yes, and we're now posting on Mondays, so look for
Speaker 1: the uploads on Monday morning.
Speaker 2: And we hope that you will go on our Facebook
Speaker 2: site which I and B Podcast.
Speaker 1: And send us a question that ask at itch not
Speaker 1: dot com Okay, so.
Speaker 3: Are you ready?
Speaker 1: Yeah, Okay, this is going to be a whirlwind because
Speaker 1: this is the craziest, most amazing thing I can think of.
Speaker 1: There are three major events that I know of in
Speaker 1: my lifetime sort of in my lifetime that absolutely revolutionized
Speaker 1: medicine as we know.
Speaker 3: It just totally changed the human species.
Speaker 2: Detail it soundsl.
Speaker 1: So the first is antabotics. What have antibotics done for humans?
Speaker 1: Doctor Miller cured like death, repentuated eighty percent society, So antibotics.
Speaker 1: The second most tragic, crazy thing that happened total misadventure
Speaker 1: is the lidamide. So this was in the nineteen fifties
Speaker 1: and sixties during the valium culture. Mother's Little Helper, make
Speaker 1: you happy, and so thalidamide was an anti vomit morning
Speaker 1: sickness drug and it turned out to cause horrible birth defects.
Speaker 1: Luckily our FDA, which some people don't like very much,
Speaker 1: but they did not approve in the United States, so
Speaker 1: a lot of American babies were spared from the limb deformities.
Speaker 1: But thalidamide was this amazing feel good drug in the
Speaker 1: fifties and sixties for pregnant women, but caused horrible birth
Speaker 1: defects and a whole generation of birth defects. So horrible,
Speaker 1: horrible misadventure. But what's crazy amazing, like the best of
Speaker 1: times the worst of times, is this gel one revolution.
Speaker 1: And I have not seen any other drug or treatment
Speaker 1: that falls into this kind of crazy madness of exploration
Speaker 1: and benefits. And so we're going to talk about GLP
Speaker 1: ones again. This is an updated version. Karen Nicol did
Speaker 1: a really good episode previously, check that out if you
Speaker 1: would like. But things have changed in months, definitely within
Speaker 1: the last year. But every week there's new and new things.
Speaker 1: So we're going to divide this episode into sort of
Speaker 1: an introduction and then what GLP ones are actually approved
Speaker 1: for and how that sort of got started, and then
Speaker 1: we're going to take a break and come back and
Speaker 1: talk about all of the possibilities and the proposed mechanisms.
Speaker 1: A lot of them are thought of and sort of
Speaker 1: hinted at by response to therapy, but not documented in
Speaker 1: really good clinical statistical trials. And then we're going to
Speaker 1: have a last segment of the possible side effects, which
Speaker 1: are kind of interesting when you start thinking about mechanisms
Speaker 1: of how the GLP actually works.
Speaker 2: And for our listeners, that don't know. What GLP one
Speaker 2: receptor agonists are is glucagon like peptide receptor agonists, and
Speaker 2: so these offer all kinds of benefits for metabolic, cardiovascular, renal,
Speaker 2: and weight related benefits. So we'll we'll dive in.
Speaker 1: Yeah, so glucagon is produced in the liver, and agonist
Speaker 1: means that we're going to stimulate the receptors and so
Speaker 1: molecularly that's how these things work.
Speaker 3: And so we started off.
Speaker 1: Do you remember when they first got approved three years
Speaker 1: ago maybe four?
Speaker 3: Yeah, so so.
Speaker 1: Not that long ago in the grand scheme of things,
Speaker 1: and they were first approved. You remember the first drug
Speaker 1: that was approved.
Speaker 2: The first one was sex Sinda and.
Speaker 3: It was approved for weight loss. Weight lossbetes that.
Speaker 2: They are a glue tide. It was indicated for what
Speaker 2: loss Victosa, which was the branded other version. With all
Speaker 2: of these classes, they get branded in different ways, and
Speaker 2: so the branding of Victosa was to decrease cardio event
Speaker 2: cardiovascular event reduction in patients with diabetes and established cardiovascular disease.
Speaker 1: So very specific prescribing guidelines, and so I would bet
Speaker 1: that when it first came out, you didn't really prescribe
Speaker 1: it to a huge number of patients.
Speaker 2: On the cardiology side. We didn't dive in initially.
Speaker 1: That's accurate, okay, So and this is just kind of
Speaker 1: back up a step, and then we're going to take
Speaker 1: a short break and come back with more detail. But
Speaker 1: to back up a step, this is one of the peptides.
Speaker 1: And peptides are all trendy now, but you need to
Speaker 1: kind of understand what peptides are. They're simply proteins that
Speaker 1: are found in the human body and interesting like other
Speaker 1: drugs that are patented and drug companies like Pfizer or
Speaker 1: Eli Lilly can have a patent on it. The Supreme
Speaker 1: Court decided that these peptides are human proteins because they're
Speaker 1: part of the human normal anatomy system, that they're not patentable.
Speaker 1: So these peptides are very specific and they have pros
Speaker 1: and cons They have benefits and side effects depending on
Speaker 1: exactly what the peptide is and what it does. So
Speaker 1: we're going to take a short break here and then
Speaker 1: we're going to come back and talk about the proposed
Speaker 1: and approved guidelines and treatment possibilities for these glp ones.
Speaker 3: Stick with us.
Speaker 1: It gets really interesting and really crazy from here. It's
Speaker 1: magical medicine moments. So hang with us.
Speaker 3: All right, we're back. I hope he stayed with us.
Speaker 1: So now we're going to talk about all of the
Speaker 1: different proposed treatments and treatments for these GLP ones and
Speaker 1: it gets it gets really interesting. So just as crazy
Speaker 1: as antibotics and pholidamide, where these GLP one started off
Speaker 1: with this little bitty niche kind of treatment protocol and
Speaker 1: now it is just crazy what they're showing to have
Speaker 1: benefits for. So from the data side of things, Stephen,
Speaker 1: what what are they actually used for and prescribed for?
Speaker 3: Right now?
Speaker 2: Yeah, so follow me into the weeds a moment.
Speaker 3: Yes, I like weeds. Yeah, data is good, give me
Speaker 3: a good action.
Speaker 2: And so initially we talked about sex and and nick tosa,
Speaker 2: and then the next generation was seema glue tide, which
Speaker 2: was ozimpic, and then Rightbelsa's and we go by and
Speaker 2: they're all it's interesting how as they've been branded, they
Speaker 2: the branding has has been approved for certain different indications.
Speaker 2: And so this is why people will meet barriers at
Speaker 2: the pharmacy counter if the drugs not written under the
Speaker 2: certain indication that it's approved for. And so for example,
Speaker 2: we go V is for weight management and obesity with
Speaker 2: weight related comorbidities, which is kind of a broad label and.
Speaker 1: That could be anything from diabetes, pre diabetes, even cancer
Speaker 1: is related to abusie.
Speaker 2: It is also indicated for cardiovascular event reduction and obese
Speaker 2: patients with established cardiovascular disease, so anybody with atherosclerosis. And
Speaker 2: then it is also indicated for metabolic dysfunction with fatty
Speaker 2: liver disease, specifically looking more into fibrosis of the liver.
Speaker 1: So glucagon is liver produced and so that's where this
Speaker 1: whole mechanism kind of.
Speaker 3: Resides in the body. So how do they so all
Speaker 3: of these peptides are similar in cross reaction.
Speaker 2: Yeah, so it wasn't done because they have to give indications.
Speaker 1: Right, but do the pharmacist and the providers if so,
Speaker 1: if they have a lot of overlap, but are they prescribing?
Speaker 1: You want you want treatment A, and so you do
Speaker 1: drug A, and you want treatment B, so you do
Speaker 1: drug B even though both drugs will do A.
Speaker 3: That's great.
Speaker 2: And so in the clinical setting, if you are prescribing,
Speaker 2: say for example, you're prescribing zep bound, which is tears
Speaker 2: zeppatide and it's approved for chronic weight management and obstructive
Speaker 2: sleep apnea. And if the patient doesn't have those disease processes,
Speaker 2: but yet they may have cardiovascular disease, then they would
Speaker 2: be covered for we go Vy, which has the cardiovascular indication.
Speaker 1: So that becomes an insurance paperwork kind of thing. But
Speaker 1: as far as the drug is actually the mechanism of action,
Speaker 1: does it really matter which one tick and then some
Speaker 1: maybe once you're next summer, once a day. They now
Speaker 1: have oral drugs because it's much cheaper and easier to administer,
Speaker 1: so their injecting devices are actually quite expensive.
Speaker 2: Yeah, so there's oral we go Vi, which is now available.
Speaker 2: There's Rybelsis, which is semaglutide as well, and it has
Speaker 2: the indications for diabetes cardiovasco or men reduction in patients
Speaker 2: with type two diabetes melitis.
Speaker 1: So we're kind of in this situation where we have
Speaker 1: lots of different drugs and the paperwork kind of regulates
Speaker 1: which drug gets which diagnosis and which treatment, but in reality,
Speaker 1: all of the drugs kind of do similar things and
Speaker 1: they have an expanding list of benefits.
Speaker 2: Yeah, so patients just need to discuss this with their
Speaker 2: prescribing provider to make sure that whatever drug is written
Speaker 2: is written under the labeling that's appropriate.
Speaker 1: Okay, otherwise you're going to get pushed back from your
Speaker 1: insurance company.
Speaker 3: That's right. So I'm going to.
Speaker 1: Read a list of all of the proposed theoretical benefits
Speaker 1: that may or may not have been proven with really
Speaker 1: good statistical studies based on tens of thousands of people.
Speaker 1: But I want you first to tell me what the
Speaker 1: actual approved indications are.
Speaker 2: So really you want to break the benefits down into
Speaker 2: three major categories, or four major categories. One is glycemic.
Speaker 3: Control, which is sugar dibe.
Speaker 2: Like glucose, and the other is weight loss, The other
Speaker 2: is cardiovascular benefits, and then of course renal protection, and
Speaker 2: then I left off one, which is the fatty liver indication.
Speaker 1: Okay, So those are the indications. But what gets really
Speaker 1: crazy and why this drug is so amazing is that
Speaker 1: it's one of the moments in medicine where the expected
Speaker 1: benefits were fairly narrow and limited, and then what the
Speaker 1: patients are actually experiencing has just exponentially exploded. So under
Speaker 1: weight loss, for instance, your joints get better. Under weight loss,
Speaker 1: your libido gets better. So it's just this crazy exponential,
Speaker 1: expansive list of benefits that these drugs have, even into depression, anxiety,
Speaker 1: drug addiction.
Speaker 2: So on my end, I really pitt because I'm work
Speaker 2: in cardiology. You look at just so, cardiovascular death as
Speaker 2: the number one leading cause of death in the United States, right,
Speaker 2: So they did this meta analysis, which was ten clinical
Speaker 2: trials looking at seventy three hundred and fifty one patients.
Speaker 2: That's a huge number of patients. And so major adverse
Speaker 2: cardiovascular events such as stroke, cardiovascular death, and non fatal
Speaker 2: am I were reduced by fourteen percent, heart failure hospitalizations
Speaker 2: were reduced by fourteen percent, and then all cause mortality
Speaker 2: for dying from anything was reduced by about twelve percent.
Speaker 2: So just looking at the one indicated group, the major
Speaker 2: reductions in depth are impressive with this drug class.
Speaker 1: Yeah, and anything above ten percent is really pretty significant.
Speaker 1: So Okay, we're going to take a short break and
Speaker 1: then we're going to come back and talk about the
Speaker 1: other benefits. So if they look at these studies and
Speaker 1: they're more and more of them, So we have now
Speaker 1: hundreds of thousands of patients globally that are on these medications,
Speaker 1: and what they do is they say, well, what else
Speaker 1: is happening in these groups of patients? So anything above
Speaker 1: ten percent is really impressive. But when we come back,
Speaker 1: we're going to talk about some of these unexpected things,
Speaker 1: like a thirty percent reduction in cancer risk.
Speaker 2: And I think it's really really important for our listeners
Speaker 2: to understand that when we're looking at some of these benefits,
Speaker 2: that most of those things are coming out of subgroup
Speaker 2: analysis from these studies. So it may not be the
Speaker 2: indication for the drug, but certainly benefit was seen and.
Speaker 1: More evidence is needed before it's a proven So we
Speaker 1: have correlation but not causation yet. Okay, we're going to
Speaker 1: take a break and then we're going to come back
Speaker 1: and talk about these kind of amazingly weird, crazy things
Speaker 1: that this drug therapies can do. Okay, hang tight and
Speaker 1: join us on the other side. Hey, I hope you
Speaker 1: made it back with us.
Speaker 3: So what we're going to do is I'm going.
Speaker 1: To read a list of all of the proposed benefits
Speaker 1: and doctor Miller here is going to chime in with
Speaker 1: some data if he has any kind of opinion about it.
Speaker 1: So I looked up on Claude. Actually is what I've
Speaker 1: switched to you now from chat, and I came up
Speaker 1: with sixty five different proposed benefits of GLP one and
Speaker 1: they're grouped into kind of specific organ systems. So cardiovascular
Speaker 1: benefits are pretty well done.
Speaker 2: So we already yeah, we already touched on.
Speaker 1: That, and that's that's even down to like reduced hospitalization
Speaker 1: visits associated reduced hypertension, and then metabolic benefits, which are
Speaker 1: global and these are going to be related to weight
Speaker 1: loss and sugar insulin diabetes, and when you start affecting
Speaker 1: in a beneficial manner, that whole pathway, it pretty much
Speaker 1: relates to everything else. It relates to sex, drive, to joints, exercise,
Speaker 1: just pretty much whole morbidity, which is your overall disease.
Speaker 1: Accumulation is improved. Hepatic disease. So you mentioned fatty liver disease,
Speaker 1: but actually liver enzymes will go down, so if you
Speaker 1: have any kind of associated with liver issues.
Speaker 2: And the day Lily is strong on that in that
Speaker 2: the indication for these drugs is there for fatty liver disease.
Speaker 2: You skipped over the whole renal I'm.
Speaker 1: Getting there, okay, yeah, okay, So and we'll come back
Speaker 1: to renal disease. So you know, kidneys, Like, who would
Speaker 1: think that kidneys are I wouldn't think that kidneys are
Speaker 1: associated with like weight loss drug But so how are
Speaker 1: kidneys benefited?
Speaker 2: Yeah, so GLP one a's decreased micro albumin area or
Speaker 2: albuminary and slow EGFR decline. There's a particular study called
Speaker 2: the Flow trial which looked at semaglue tide and it
Speaker 2: showed there was a twenty four percent reduction in kidney
Speaker 2: outcomes such as EGF to our decline, kidney failure, and
Speaker 2: kidney slash cardiovascular death. So pretty four percent.
Speaker 1: So he said a lot of that's really he works there. Yeah,
Speaker 1: anything about ten percent is impressive. So what he's basically
Speaker 1: talking about is how well the kidney processes fluids and
Speaker 1: toxins and GFR is glomyl glomerular filtration rates, and that's
Speaker 1: kind of what the kidney does, It filters out.
Speaker 2: And there was a meta analysis, by the way of
Speaker 2: all of that data, which is a huge It still
Speaker 2: seventeen percent reduction and composite kidney outcomes across the class.
Speaker 2: So that's a fairly impressive.
Speaker 1: And who would have thought kidneys so neurologic disorder, so
Speaker 1: alcoholism and liver disease. That kind of makes sense that
Speaker 1: if you're improving liver function, that doesn't mean We were
Speaker 1: talking with our friends last night who are into all
Speaker 1: of these vitamin supplements to improve their health, and I
Speaker 1: pointed out that the biggest improvement would be to stop
Speaker 1: drinking alcohol, which is a neurotoxin.
Speaker 2: YEA, So I will point out to our audience that
Speaker 2: they're yes in the subgroup analysis there, which means not
Speaker 2: the primary outcome for the trial, but they broke down
Speaker 2: the subgroups and they looked at people's alcohol intake, and
Speaker 2: early signals were found for reducing alcohol and substance use,
Speaker 2: although this is not totally clear and needs further investigation.
Speaker 1: So I was talking about liver health and the effect
Speaker 1: of the toxic alcohol, and we're recording this as we're
Speaker 1: having a glass of wine, so we definitely are not
Speaker 1: anti alcohol, but so the liver health benefits. But you're
Speaker 1: actually talking about behavior and addiction. So the amount of
Speaker 1: alcohol consumed, and this also happens with weight, that the
Speaker 1: food drive, the annoying, obsessive, compulsive food thoughts get reduced,
Speaker 1: and this is a huge impact on addiction.
Speaker 2: Yeah, the central nervous system effects are not clearly understood
Speaker 2: yet and so certainly need further investigation.
Speaker 1: Yeah, but the benefits for addictive behaviors, even shopping addiction,
Speaker 1: porn addiction, There are all of these sort of hints
Speaker 1: that these drugs may be beneficial.
Speaker 2: So again in the subgroups where we looked at trends
Speaker 2: on the forest plots, we saw that the data trended
Speaker 2: toward the SGLT two our GLP one.
Speaker 3: A yeah crazy, so okay, And what about Alzheimer's.
Speaker 2: So neuro degenerative disease. The preliminary evidence suggests some potential
Speaker 2: benefits in preventing dimension improving Parkinson's disease. Again, these are
Speaker 2: investigational poorly understood, but when you looked at subgroups, certainly
Speaker 2: there was some indication that this needed to be evaluated further.
Speaker 3: Do we have a proposed mechanism?
Speaker 2: Is it?
Speaker 3: We don't.
Speaker 2: Again, the whole central nervous system impact of this class
Speaker 2: is poorly understood.
Speaker 1: And this is just what blows my mind is that
Speaker 1: you know, this was launched for a very narrow, limited
Speaker 1: diagnosis set and just the potential impact. I mean, there
Speaker 1: are even discussions if you know entire populations. If every
Speaker 1: American citizen or Australian or Canadian should be put on
Speaker 1: these drugs just for overall health and well being, it's
Speaker 1: just amazing. So okay, respiratory impact. So you mentioned sleep apnea,
Speaker 1: So how is that benefit.
Speaker 2: Tears zeppetide is approved for obstructive sleep apnea? Is a
Speaker 2: web bound Well we don't know. Again, so there's the
Speaker 2: whole central nervous system piece that we don't understand. But
Speaker 2: then there's also that with obesity comes this pickwick in physiology,
Speaker 2: which is where the diaphragm so they really excurred and
Speaker 2: so then it's nine.
Speaker 1: Predominal fat and you just mechanically can't breathe.
Speaker 2: Yeah, So it's indicated for moderate to severe abstruct restrictive
Speaker 2: sleep apney and patient in adults with obesity.
Speaker 1: So even going to like arthritis and knee osteoarthritis and
Speaker 1: pain and cartilage degeneration. And that's probably related to weight
Speaker 1: that if you lose one hundred pounds with these drugs,
Speaker 1: then that's one hundred pounds less that your knees have
Speaker 1: to absorb.
Speaker 2: Yeah, So there is symptomatic improvement with this class in
Speaker 2: knee specifically knee osteoarthritis, and we think that is probably
Speaker 2: related to, you know, just the weight tension on the joint,
Speaker 2: although we just don't know.
Speaker 1: Okay, women's mental stricles become more stable and predictable and regulated.
Speaker 3: What the hell's up with that?
Speaker 1: Like, how does a weightless drug cause better menstrual suz.
Speaker 2: So if you just think about it, that is where
Speaker 2: hormones are stored, right, and so then you start reducing
Speaker 2: fatty tissue in central obesity, and then you start shifting
Speaker 2: hormones and so people do have some hormonal shift that occurs.
Speaker 1: Again, this just blows my mind. This is one of
Speaker 1: the most amazing things I've ever even contemplated. We talked
Speaker 1: about neurodegenerative diseases like Alzheimer's.
Speaker 3: What about stroke reduction? Is there any benefit for that?
Speaker 2: The drugs are indicated for cardiovascular event reduction, which includes stroke,
Speaker 2: so of all cardiovascular disease, so that's included there yet Okay.
Speaker 1: And then I've talked about my chronic migraines. This is
Speaker 1: researching this. I learned this that there's actually some evidence
Speaker 1: that migraines become less severe and less episodic, so fewer
Speaker 1: migraines per month on these trucks.
Speaker 2: Yeah, so this is evidence coming from the subgroup analysis
Speaker 2: and again poorly understood, not absolutely indicated, So make sure
Speaker 2: our audience understands that, but also knowing that there is
Speaker 2: some potential potential for improvement in those symptoms.
Speaker 1: Just so I've rethought starting to take these. I'm not
Speaker 1: terribly obese, and actually I'm very sensitive to the side effects,
Speaker 1: which we're going to cover in the next section. But
Speaker 1: I've actually restarted these for my migraines. I've had horribly
Speaker 1: uncontrolled migraines. Okay, so then what about reproductive benefits. We
Speaker 1: talked about the menstrual cycles that reproductive fertility seems to
Speaker 1: be increasing in this way.
Speaker 2: Yeah, so again, you know, you look at something when
Speaker 2: you look at a syndrome like PCOS polycystic ovarian syndrome,
Speaker 2: which can contribute to some infertility issues, and it's kind
Speaker 2: of a pre diabetic state and that impacts fertility. Again,
Speaker 2: fatty tissue stores hormones and shifts hormones, and so we
Speaker 2: just don't really know, but there is some some data
Speaker 2: and evidence in the subgroups to indicate there might be
Speaker 2: some benefit there. Just mind blowing, well, I think, yeah,
Speaker 2: so I think that they're at my pliants. So we
Speaker 2: in the US, all food is readily available everywhere. You
Speaker 2: drive down the highway and there are signs everywhere, and.
Speaker 3: We eat French fries for a week more.
Speaker 2: Then we go to a restaurant and we're served a
Speaker 2: three person portion and we continue to eat that way
Speaker 2: and our bodies can't, uh can't keep up, and so
Speaker 2: then there's this shifting of hormones that all of the
Speaker 2: obesity problem does impact neuroentocrine system, central nervous system, cardiovascular system.
Speaker 2: And so this impact is what we're trying to understand better.
Speaker 1: And then what actually stimulated us researching this and do
Speaker 1: in this episode was recent information that was just released
Speaker 1: on cancer rates. Yeah, so anything above ten percent is impressive,
Speaker 1: and the recent data looks at reduction in cancer all
Speaker 1: sorts of cancer, prostate, ovarian, breast cancer of twenty to
Speaker 1: thirty percent.
Speaker 2: So again, the latest information on this particular evidence is
Speaker 2: that we don't really know. An Umbrella review found no
Speaker 2: substantial association between GLP one ra's use and cancer risk
Speaker 2: across thyroid, pancreatic, and overall cancer outcomes. So we don't know,
Speaker 2: and I think it's important for people to really understand
Speaker 2: that in that certainly port eating can cause all kinds
Speaker 2: of GI cancers and this and that.
Speaker 1: So one of the reason he mentioned thiraid is one
Speaker 1: of the contraindications in the next section. We're going to
Speaker 1: take a break and come back with side of But
Speaker 1: one of the contraindications of this drug was a genetic
Speaker 1: tendency towards thyroid cancer, and so they were specifically looking
Speaker 1: at does this drug really cause an increase in thyroid
Speaker 1: cancer with people with this genetic trait, And it turns
Speaker 1: out that a huge meta analysis of ninety different studies
Speaker 1: that there's no correlation. So that's not specifically talking to
Speaker 1: the reduction in breast cancer. That's just talking about one
Speaker 1: of the potential side effects. So we're going to take
Speaker 1: a break here and then we're going to talk about
Speaker 1: the side effects when we come back. Sound good, Okay,
Speaker 1: we'll be right back. Hang with us again. Mind blowing
Speaker 1: crazy therapy, Alice in Wonderland, magic medicine kind of stuff.
Speaker 1: We'll be right back. Okay, we're back. I hope you
Speaker 1: stayed with us. So now we're kind of in the
Speaker 1: side effect the benefits of all of these things are
Speaker 1: expanding and in ways that are again mind blowing for me.
Speaker 1: But so the two big really scary things three probably
Speaker 1: that were associated with these therapies was the genetic risk
Speaker 1: of thyroid cancer, and you just mentioned that, studies now
Speaker 1: show that's probably not as significant as what it was
Speaker 1: initially thought.
Speaker 3: That is.
Speaker 1: The other big issue was retinal blindness associated with our
Speaker 1: arteritis so vessels in the retina, and huge large meta
Speaker 1: analysis multiple studies show that the risk of blindness with
Speaker 1: these drugs is also pretty negligible.
Speaker 2: So I think it's important also to point out that
Speaker 2: that very same meta analysis that was done showed there
Speaker 2: was no significant increase for hypoglycemia. So people get all
Speaker 2: caught up because they're on all these things, and so
Speaker 2: they're concerned about their blood sugar dropping. And certainly if
Speaker 2: you can.
Speaker 3: Cause you to feint to pass out, have car accidents.
Speaker 2: If you are on insulin or diabetic agents, certainly at warrants,
Speaker 2: as you lose weight, that your requirement for insulin will
Speaker 2: go down, or your requirement for those medications may go down.
Speaker 2: So it's really important to keep monitoring and discuss that
Speaker 2: with your provider if.
Speaker 1: You're disabetic doing these drugs, you absolutely need very frequent monitoring.
Speaker 3: By your provider. Also, that's exactly what these drugs affect.
Speaker 2: That meta analysis also did not show an increase in
Speaker 2: the risk of retinopay or pancreatic events, and so that
Speaker 2: really was reassuring to the population that those were not
Speaker 2: going to be issues unless you had a previous history
Speaker 2: of some pancreatic you know, right.
Speaker 1: So, pancreatitis is the pancreas produces digestive enzymes that get
Speaker 1: released in the small intestine and they help break down
Speaker 1: proteins and carbohydrates and absorb various nutrients. So when you
Speaker 1: have like a really really bad faty meal, or if
Speaker 1: you're predisposed and you have leaking of these gastric pancreatic enzymes,
Speaker 1: you get a parrotinitis and really severe pain, and it
Speaker 1: can be life threatening. So that was one of the
Speaker 1: potential side effects, and I will say that that is
Speaker 1: still probably the group of side effects that are most prominent.
Speaker 2: Well, the most prominent are nausea, vomiting, and diarrhea.
Speaker 1: Which I'm very very sensitive to these drugs. I've been
Speaker 1: I tried to go on various different ones over the
Speaker 1: course of a couple of years, and I'm trying them
Speaker 1: again for my migraines, but I am extremely sensitive to
Speaker 1: the nausea aspect. My daughter, genetically related to me, actually
Speaker 1: tried these drugs. She was probably one hundred and fifty
Speaker 1: pounds overweight, ended up in the hospital with chronic vomiting
Speaker 1: for three days that she couldn't control. And those side
Speaker 1: effects are the most common and they can definitely be
Speaker 1: diminished by dose.
Speaker 2: Regulation, so you can mitigate most of the nausea, vomiting,
Speaker 2: and diarrhea. BA gradual dose titration is very effectively kind
Speaker 2: of you know, microdose at the front end and work
Speaker 2: your way up, which is what is recommended and certainly
Speaker 2: within the labeling of these drugs. And then as we
Speaker 2: move forward, some of the emerging concerns, which we will
Speaker 2: dive into a bit is potential loss of muscle and
Speaker 2: bone mass with weight loss.
Speaker 1: Yeah, so this is the ozimpic face, is what it's
Speaker 1: been called on Doctor TikTok, where you lose fat and
Speaker 1: some muscle, but mainly the fat in the muscle, and
Speaker 1: then you start looking kind of skeletal, and a lot
Speaker 1: of celebrities we're just talking to our other daughter on
Speaker 1: this is Father's Day when we're recording this, and we're
Speaker 1: showing pictures of celebrities that look pretty skeletal.
Speaker 3: Yeah, and that's definitely one of the side effects.
Speaker 1: So how does that happen, Like, what's the mechanism of
Speaker 1: that skeletal appearance.
Speaker 2: Well, so there's some concern of true muscle loss. But
Speaker 2: then also, and.
Speaker 1: We talked previously that muscle mass is a huge metabolic
Speaker 1: organ and if you're losing muscle mass, all sorts of
Speaker 1: bad things can happen.
Speaker 3: So we like muscle.
Speaker 2: So there's muscle tissue, skeletal muscle tissue, but then there's
Speaker 2: also the fat. As we get fatter, deposits into muscle
Speaker 2: tissue and so then the muscle gets more lean. Additionally,
Speaker 2: then you've got the loss of subcutaneous tissue and so fat.
Speaker 1: Yeah, most of your dormis or that if you can
Speaker 1: pinch your skin, most of what you're pinching is actually fat.
Speaker 2: And there are ongoing studies looking at that particular issue.
Speaker 2: So I think we just need to make sure that
Speaker 2: we know that you know, when we're losing weight, we
Speaker 2: want to achieve healthy weight loss. We want to make
Speaker 2: sure we keep our protein intake high while we're losing weight.
Speaker 1: So then one of our friends the other night brought
Speaker 1: up could you take other peptides like a growth hormone
Speaker 1: analog to then stimulate muscle development, And we talked about
Speaker 1: all of these peptides having benefits and side effects, and
Speaker 1: the problem with growth hormone therapy is that it can
Speaker 1: cause diabetes. So you know, you want to be careful
Speaker 1: what you're mixing and matching here that if you're having
Speaker 1: a side effect of muscle loss, you know, don't necessarily
Speaker 1: rely on another treatment quick and easy fix, because that
Speaker 1: can have side effects too. So interesting, before we get
Speaker 1: into weird things, any other kind of documented side effects
Speaker 1: that you'd like to talk about?
Speaker 2: Those are the big ones. I did have a question
Speaker 2: for you, Keith in that in the bitinery medicine world,
Speaker 2: what is the space looking like for animal health and
Speaker 2: are we using GLP one ris for animals and are
Speaker 2: they documenting the same side effects that we're having and
Speaker 2: clearly some are not documentable.
Speaker 1: But yeah, so let me answer that in a second
Speaker 1: after I talk about the other kind of weird human
Speaker 1: side effects.
Speaker 3: The other weird thing that's.
Speaker 1: Happening with these drugs and side effects that we really
Speaker 1: don't quite know and understand relates to the gastric motility.
Speaker 1: So all of these drugs, you know, affect gastric motility, appetite,
Speaker 1: eating calories in bulk fiber. Just you're eating less, you're
Speaker 1: pooping less, your gi system slows down, and what that
Speaker 1: seems to be doing is decreasing the absorption of some drugs.
Speaker 2: Yeah, so he's speaking to gastroparesis, which is one of
Speaker 2: the potential side effects flowing down of the gut. And
Speaker 2: certainly when the gut slows down and you take other
Speaker 2: medications and then the transit time for those medications in
Speaker 2: the gut is decreased and so absorption is higher.
Speaker 3: Usually lowers the concern.
Speaker 1: So the problem with this, and it could be higher too,
Speaker 1: But the problem is that if you're on certain drugs
Speaker 1: that are really really important, like statins for your cholesterol,
Speaker 1: and suddenly your drug dose goes down or up, that's
Speaker 1: a problem. Birth control. If you're taking birth control and
Speaker 1: it becomes less effective, less absorbed, and you get pregnant,
Speaker 1: that's a pretty big side effect.
Speaker 2: So the point that I was making with the higher
Speaker 2: absorption drug is that the pharmacode dynamics have now changed
Speaker 2: and we don't.
Speaker 3: Know yet, so you have to be careful though. Yeah.
Speaker 2: Yeah, so I think more information needs to come forth about,
Speaker 2: you know, dosing with other medications on board. However, if
Speaker 2: antibotics for NOMEN in their studies, you know, the drug
Speaker 2: drug interactions are not super impressive.
Speaker 3: So yeah, but it's a concern.
Speaker 1: I mean, certainly if one of the side effects is
Speaker 1: getting pregnant, that you know, we need to kind of
Speaker 1: know about that. The other thing that we really don't
Speaker 1: know is what's going to happen in thirty years when
Speaker 1: you stop these drugs the weight gain returns?
Speaker 3: Is that correct?
Speaker 2: It does? And so the point being that if certainly
Speaker 2: for the indicated use, what we don't know and what
Speaker 2: we hope to have more information on is maintenance dose.
Speaker 2: Is there a maintenance dose or do we stop?
Speaker 3: Yeah, could you use this?
Speaker 2: So we just don't know that we don't have or
Speaker 2: take it.
Speaker 3: We don't have once a year, or we.
Speaker 2: Don't have you know, twenty year studies to look at
Speaker 2: outcomes that far out. And so these are question unanswered
Speaker 2: questions on the human side.
Speaker 1: Yeah, So going back to veterinary medicine. We're talking with
Speaker 1: some friends about this last night, and there are a
Speaker 1: lot of medications that on the veterinary side we can
Speaker 1: use them because they have a lot of side effects.
Speaker 1: But the dogs only live fifteen years, where humans live
Speaker 1: potentially ninety years, and so if you're on a drug
Speaker 1: for thirty years, that's a lot different than being on
Speaker 1: a medication for three years. So there is a there
Speaker 1: is an absolute difference in a lot of medications in
Speaker 1: the veterinary world that we can use and avoid the
Speaker 1: side effects simply because the lifespan is much short. And
Speaker 1: that's sad, but that's just the reality. The other question
Speaker 1: that you had asked before is are we using these
Speaker 1: drugs in veterinary medicine, And the answer is that we're
Speaker 1: beginning to. They're very expensive, and so a cost price
Speaker 1: threshold is a little bit of.
Speaker 2: A So are there any studies among dogs or cats?
Speaker 1: Is actually where most of the interesting information is. So
Speaker 1: most indoor cats are obese as they get older. And
Speaker 1: what's also interesting is that they have a lot of
Speaker 1: very annoying OCD food seeking behavior tendencies that drive you
Speaker 1: own are crazy. So my daughter's cat when we go
Speaker 1: visit non stop, is begging, meowing, buying at your ankles,
Speaker 1: wanting food and very healthy weight cat but just once food,
Speaker 1: NonStop and if you give it food, then it vomits
Speaker 1: because it ate too much food. So these drugs, actually
Speaker 1: they're not big studies. So we have like six animals here,
Speaker 1: ten animals here, very very small compared to the human side,
Speaker 1: but they are showing benefit in obesity and diabetes is
Speaker 1: not that common in dogs, much more common in cats,
Speaker 1: and so definitely this is something that's being explored across species,
Speaker 1: and you know, it seems to have a lot of benefit.
Speaker 1: But again mind blowing crazy, you know, unpredictable. Human medicine
Speaker 1: had no glimpse of where this drug was headed in the.
Speaker 2: Potential, so in animal size, it looks like exanatide is
Speaker 2: the drug that's being used.
Speaker 3: I was just looking at me.
Speaker 1: We use a lot of compounded drugs, so the Supreme
Speaker 1: Court said that you can't patent these or trademark copyright
Speaker 1: these drugs, and so there are a lot of compounded
Speaker 1: drugs available. If we're using brand names, it gets really expensive.
Speaker 2: It appears in cats there was a forty percent diabetic
Speaker 2: remission versus twenty percent in control, so kind of again about.
Speaker 1: Ten percent how many cats though, so it was it
Speaker 1: was a small stuff.
Speaker 3: Yeah, and that's the problem.
Speaker 2: So the confidence intervals are really wide and so trusting
Speaker 2: that data is.
Speaker 3: Based on the human data. I mean, it definitely looks
Speaker 3: like it has a lot of potential.
Speaker 2: Sport to five cats by the way, five cats, Yeah,
Speaker 2: that's not really a well that's medic caase study case report.
Speaker 1: Okay, So that's our update on the GLP ones. Please
Speaker 1: send us any questions or comments to ask at itch
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Speaker 1: dogs and cats, and visit our websites at itchy and
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Speaker 3: Stay well, stay safe, get up and move Okay, Bye
Speaker 3: bye guys,