GLP1s Masterclass transcript

okay all right hi everyone um I'm having some technical difficulties actually we just lost power I think because of the weather here in New York and um and I lost internet access which I'm hoping um is back and will be okay for a bit um if there are any issues please comment um so that we know that um uh okay that we know that things are okay um so you can um Post in the chat or Q&A um I have Kyle with me uh she's on my marketing team and so she's going to be keeping track of uh the chat box while I do the presentation I thought I would do today since we're doing a master class on uh gp1s um what I thought was since it's kind of a complex topic um I couldn't resist putting together a little PowerPoint slide presentation and um I'm going to try to keep it pretty basic but I think it's it's really great to kind of see um the some some some illustrations and diagrams and things like that to try to understand the concept better and I think it makes it a little easier um to you know again understand what we're what we're talking about so I'm GNA share um I'm going to share the PowerPoint and I'll go through it and then we should have plenty of time at the end for for questions so let's uh let's get started let me put that okay so hopefully um you see that um I have a couple of QR codes for my Instagram and my website if you want to take a look if you're not familiar um and then um sort of Let's uh yeah let's let's uh dive in I have a little disclaimer just to be very clear right that this is all educational and and informational um and you know obviously everything I'm talking about doesn't constitute any medical advice um so things that that are that are specific to you in your case you should always consult your own uh physician for my patients who are listening you know you know let's talk at another time about these things but um but you know me and I and I think many of you know me that I love to share my experiences and you know the new research I'm doing and so I was really excited to to share what what um what's uh the latest on um gp1s but also how it relates to the stuff that I treat which is immune dysfunction massel Activation Syndrome uh chronic uh infections Etc um so uh I want to start with some Basics um you know I talk a lot about at least my patients know this I talk a lot about insulin resistance and I really think that um unfortunately the majority of people um that have medical issues have some level of insulin resistance and um and and really what insulin does so we're going to talk about about what the the role of insulin is and how your body utilizes it so in a in a perfect scenario um what's supposed to happen is when you eat the food that you eat breaks down to sugar or glucose the glucose um has to be utilized by your cells for energy um and but in order for the cells to to get the glucose into them there's a specific um mechanism for that because glucose cannot just float into the cell the cell has a door right and it's sort of you see this here these are like they're called glucose channels I think of it as a door door the door is closed if there's glucose in the bloodstream that has to get into the cell you need insulin and insulin is released by your pancreas immediately when it's when you're exposed to glucose and Insulin binds to receptors on the surface of the cell The receptors I think of like they're just like little seat as you see here where insulin can and insulin and receptors we're going to be talking about a lot they for signaling for cell signaling so in this case insulin's released by the pancreas it sits on the receptor and it tells that glucose Channel open up and let the glucose into the cell right so we see glucose outside of the cell when the insulin sits on the on the receptors now the glucose can enter the cell now it's inside and now it can be used for energy what happens with insulin resistance is a couple of scenarios one is in some cases um the pancreas is not producing enough insulin so there's not enough insulin to sit on the receptor to tell the cells to open the glucose Channel and so then the glucose can't get into the cell and so now you have more glucose in the bloodstream and now the your glucose levels are are going up so if you check your blood sugar and maybe higher um that causes a host of things glucose and sugar in general is sticky so it's going to stick to the cells it's going to stick to the blood vessels um and that's that's part of the problem with diabetes diabetes is essentially too much sugar in the bloodstream causing um uh breakdown of you know blood vessels or inflammation in blood vessels causing inflammation in the nervous system um causing issues in the kidneys and you know other things right so so glucose is bad it's sticky you don't want it sticking to things you want to make sure that the glucose gets into the cell appropriately now the other thing that happens uh often in insulin resistance is that there actually is enough insulin produced by the um by the pancreas but these insulin receptors are not um are not sensitive to the insulin they're not responding appropriately so insulin is sitting there and saying hey hey I'm here you know open the glucose Channel but the cell is not listening and the cell is is basically Al finding it that it needs more and more gluc more and more insulin to sit on those receptors to finally get that signal transmitted the glucose channels open and the glucose in the cell okay so that's insulin resistance and in that case where there's more and more insulin produced to try to overcome this this insulin resistance insulin itself is very inflammatory glucose itself is very inflammatory and the two together is is a really perfect storm for uh for inflammatory conditions now we can pretend actually that the cell is a mass cell because it turns out that massed cells have insulin receptors on their surface it turns out that mass cells need glucose to work and so you can imagine if there are issues with insulin and glucose that mass cells may become dysfunctional we also know that mass cells read changes in the environment right we know that too much of something too little A Change is Going to trigger them and so if there's a change in blood sugar up or down you know all of a sudden there's a lot of blood sugar and then all of a sudden the insulin started working and now there's a flooding of glucose into the cell and all of a sudden the glucose in the bloodstream drops and you become hypoglycemic then the mass cells will see that that's a trigger for mass cells high low all those things are potential triggers to think about okay so the other thing to think about as we talk about insulin glucose and in sort of the management of that is just in general what glucose homeostasis is like so if you're if you're if you don't have enough um glucose okay when glucose levels are low and they can be low if there's too much insulin pulling the glucose into the cells and out of the bloodstream so now the cells are full uh maybe even too full but the bloodstream doesn't have enough and now the brain doesn't have enough so that will um signal uh the pancreas to produce a hormone called glucagon and glucagon based basically takes uh sugar out of the liver and um and and breaks it down um to make more glucose um when you eat a meal that has sugar or gets broken down to Sugar insulin is released again triggers the uptake of glucose into muscles various cells adapost tissue which is fat cells um and also if there's excess sugar the body will um uh go through a process called gluconeogenesis where it kind of like makes more sugar and kind of like stores it in the in the liver and storage of glucose in the liver can then turn into fat and and turn into a fatty liver right so I wouldn't worry too much about about all these like arrows but it's just thinking about you know the role of like we we need some glucose um for for certain cellular functions it turns out that some cells don't need glucose it turns out that the brain actually does need some glucose and and the regulation of this and what we know is that in diabetics or in pre-diabetics there really is a disruption in a lot of the processes with insulin with gluc agon and with some other proteins and peptides including this particular uh peptide called glp1 or glucagon like peptide 1 now this is a peptide it's actually released by uh certain cells in the intestines um mostly in the colon and then like in the the lower part of the small intestine and it's released almost immediately when when you eat food and its primary function is to help regulate blood sugar um and so it's working um on the pancreas so basically it's sort of sending the the signal for the pancreas to release um insulin which then you know uh then cause it helps the cells absorb and um uh allow the glucose to enter the cells okay so glp1 is a really important peptide that you need to help stimulate the release of insulin now um when we talk about drugs that um you know this what the master class was about the drugs we're talking about are called glucagon like peptide one receptor agonists so they look like the um that peptide that's produced by the intestines okay they're almost identical with very very small changes um that allow it to actually last longer in the body the natural one we have is very fast acting and very quickly um it very quickly dissipates so these drugs are are are designed you know to look like the peptide but to um to last longer and they bind to the the same receptor that the GL that gp1 binds to and it turns out that there are lots of cells in the body including the pancreas that have receptors um uh for this peptide including mass cells so if we talk about that uh that one uh drug um semaglutide um it's also on the market known as OIC or wovi um these are pure glp1 receptor agonists and they act by they activate these glp1 receptors and they send the signal to the brain uh to the gut to lots of areas I'm going to show you I'm I'm going to show you all the cells that that basically it binds to but but but we think that some of the function is related to the signaling in the brain that's telling it okay you're you're full um so stop eating um and it slows down um the rate of gastric emptying so how fast your stomach empties so if if there's more food left there for a longer period of time you'll feel Fuller and that also reduces caloric intake so that's kind of like what we what we what we know about it but the research is is really really expanding on on how we understand where these receptors are and what is happening when glp1 agonists bind to these various areas of the body so I said that it binds in the pancreas and it increases insulin secretion now for some people would think that that might be bad you don't want too much insulin right that I told I said earlier right too much insulin could be bad too but it seems that in the way it's it's stimulating the increase in insulin it's also making the cells of the pancreas uh more productive and and in that case actually over time it seems to to make the pancreas um more efficient so that initially it may cause more insulin production but over time it actually levels off because the whole body is working more efficiently um it works at the level of the the GI tract um to slow gastric emptying um to slow gastric motility um and um you know so in the variety of functions there and and some of that could actually lead to side effects and we're definitely going to talk about side effects but some of those effects are actually potentially positive we know that in the kidneys um it um reduces things like oxidative stress reduces inflammation re reduces um um uh albuminuria and and we know that in um what that means is that's that's protein that is leaking out of the kidney that uh can damage the kidney and so in like diabetics you know some diabetics wind up with kidney disease renal disease um and these these drugs or these compounds have been shown to reduce the amount of leaking in the kidney making it more efficient in in the brain um it it is seem does seem to reduce the amount of food intake interestingly it also May reduce uh the amount of water um intake and so I I have patients I definitely see this in patients that I treat where they they um uh almost forget uh to drink like they used to um so there there's that constant like they have to remind themselves because they don't have that same urge um but you know a study just came out today on um uh the effects on maybe reducing um cognitive dysfunction maybe reducing the risk of Alzheimer's um so they seem to be neuroprotective in in fat cells they seem to sort of help with a breakdown of fat lipolysis they increase the sensitivity to insulin so things can be can work properly then maybe increase Brown fat which we think is is better for the body um in muscles it makes the muscles more sensitive to insulin so that more glucose can be uh can go into the muscles making the muscles more efficient stronger if you're a bodybuilder or you like to lift weights that can have a positive effect um in bone health um this is a little bit of mixed um we know in research that that there may be a positive effect on bone we don't know if it's truly going to help osteoporosis yet in humans we haven't we don't have studies right now it seems to be bone neutral but there's some my studies that have shown that maybe it's improving um bone health potentially and so again the the lisco on what it's doing in the liver the vasculature the heart um you know lots of potentially positive effects um Now The Other Drug on the market um is tepati which is also known as mararo or Zep bound U mjara is the one that's approved for diabetes and zound is the one that's approved for obesity and this is what's called a dual an incretin um which is a glp1 receptor Agonist like the OIC and wovi but also a Gip receptor Agonist so incretins are are hormones or peptides that are released in the intestine in response to the presence of nutrients inside okay so these are incron um and these are the two um main incron that we know of the gp1 we said is the glucagon like polypeptide and the Gip is is also known as glucose dependent insulinotropic polypeptide um these are both peptides so they're a string of amino acids IDs the glp is produced mostly in the colon and the end of the small intestine the Gip is mostly made in the small intestine in the dadum and the dunum okay and again it's in response to food and nutrients and what we what we're starting to understand is that in patients who are insulin resistant pre-diabetic okay having the start of increased blood sugars increased hemoglobin A1c numbers or even in diabetics there's there seems to be a decreased release of glp1 in response to food if there's a decrease in the release of the glp1 then there's a decrease in the insulin response it's going to take longer for the insulin to get released and the right amount to be released so the cells can take up the glucose um but then it's potentially going to have all those opposite effects to what we just looked at right you don't have gp1 so now you have more inflammation now you have all these other potential Downstream effects and what we also find is that the there may be um enough Gip released in these states um of of high blood sugar but uh the response to giip seems to be decreased so there's like a resistance in diabetics pre-diabetics and those insulin resistance um and what we think is that these receptor resistance can be reversed um and possibly there it can be reversed with these drugs that we're talking about so uh this is um sort of showing what uh what we believe that Gip is doing initially we thought that Gip was only acting at the pancreas level and also like glp one increasing insulin secretion increasing the production of insulin increasing the beta cells um which are making insulin but it also happens that that the Gip seems to bind to the brain there are Gip receptors at the level of the brain Gip receptors in the bone and Gip receptors in fat cells there may be Gip receptors elsewhere but I think this is still actually some work in progress um and what we don't know for sure is if there are Gip receptors on mass cells there are gp1 receptors on mass cells we're not clear on the Gip receptors yet there's some belief that they're they're they may be there uh but but we don't know but there's certainly a synergistic effect between the glp1 and the Gip and we see on the left here is okay so if you're just going to take um the semaglutide right OIC or wovi this is where you're going to be on the left side where you're going to have increased a feeling of fullness um you're going to have more insulin decreased glucagon um but you're going to have more nausea and the laid gastric emptying um you're going to have less glucose production by the liver which is what you want because that will eventually break down the fat in the liver if you have fatty liver and the fat cells become more insulin sensitive and then if you add the Gip to it like in the tepati um mararo or Zep bound um it does some of the same things at the level of the pancreas more insulin um but in this case more glucagon as well which is interesting um but less nausea and so I definitely see that in practice where um the suag glutide definitely has a little bit more of the nausea effect particularly early on T epetite can certainly do that but I think that Gip addition does seem to decrease it there's still some delay gastric gastric emptying but again I think it's a little bit less um and what GP has been shown is to do is to um decrease triglycerides um to increase insulin sensitivity um and increased lipid buffering capacity so I think that's like you know all really important stuff and um here's just another view of how Gip and glp work um to increase the things that we you know want it to increase decrease the things that we we don't want to or we need to uh so some of the decreas and things that it's doing sometimes is is is negative like a Del decrease in gastric emptying maybe may be good for some of the side effects but bad for other side effects um some of the increasing sensitivity triglyceride clearance breaking down of fat right is is good and in fact uh the addition of Gip also seems to help with um the heart ventricular contractility has to do with the contractions of the of the heart um which um which now has been shown multiple times that there's an improvement in heart function um with these drugs so we if we concentrate on cardiovascular health the things that we are seeing in um in various studies is that not only um are these uh drugs uh decreasing blood sugar um which is then affecting the heart in positive ways but they're directly you know the The Binding of these receptors is directly having an impact on the vascular the arteries so we're seeing reduced blood pressure um we're seeing Improvement in cholesterol and in fact for some patients dramatic Improvement in cholesterol um we're seeing less buildup of plaque in the arteries and and reduction of inflammation and you're going to see over and over again that inflammation is really or decreased inflammation is really a Hallmark of of these drugs which I think is what's so exciting because we know that mass El activation syndrome and many of the other Chron complex chronic issues that I treat um are based in inflammation right or or the Hallmark features are inflammation so we're always looking for ways to decrease inflammation so if we can reduce inflammation through these Pathways and and maybe directly by binding mass cells at the glp1 receptor and stopping and stabilizing mass cells you know then we're having a systemic effect um with a reduction of inflammation and then overall Better Health and a reduction of symptoms um so so the gp1 receptor agonists are are doing a number of these things the Gip receptor um activation also um contributes to cardiovascular protection um by reducing oxidative stress and improving insulin sensitivity preventing damage to blood vessels and again I mentioned earlier that blood sugar can be very damaging to blood blood um blood yeah blood vessels are damaged by blood sugar and um and that's what actually causes plaque to build up and if we can sort of um neutralize the damage um then then we have less plaque plaque buildup so I think this is a powerful tool um uh immune Health right so again we're talking about reduction of inflammation by reducing cyto kindes I think the main pathway is through stabilization of mass cells there may be other ways that these drugs are working to reduce inflammation um I I think that they are somehow balancing the immune system and other parts of the immune system beyond the mass cell and there's some some new research that's coming out to that's that's looking at that um and um and and so uh by you know calming the immune system balancing the immune system um again we are um you know reducing inflammation the neurologic stuff is really where I think that this is going to be a a true GameChanger not that these other things aren't important um but you know I see uh really so many patients I think neurologic symptoms are by far probably um the most uh problematic um at least in my in my practice right um anxiety depression neuropathies migraines um cognitive dysfunction brain fog memory problems um I'm probably missing for some right but you can imagine that I'm I'm sure that many people here can relate either for yourself or family members or friends right neurologic health is is is really really important and um what we're finding is that these drugs and particularly maybe that combination of the glp1 and the Gip Agonist binding these receptors are protecting the brain uh from from either further damage or or maybe even reversing some of the damage um maybe reducing oxidative stress uh maybe preventing cognitive decline again there was a study that was just released um looking at 7,000 oh no 177,000 patients and uh current patients being treated and then uh thousands of other patients that had been treated with these drugs in the past and they showed um a significant decrease in uh the development of Alzheimer's specifically um we know that these drugs can decrease apoptosis or cell death so apoptosis is important like you don't you want some some of your cells to die especially if they're bad cells um but um but too much of that can also be uh really detrimental uh to the nervous system in the brain and so these drugs have a way of sort of blunting that and then improving synaptic plasticity and so what I see is patients who have had a significant uh memory issues sometimes it's working memory sometimes it's short-term memory um with time um these drugs May improve the ability to learn and to to think and again I'm not I'm not suggesting that this is a a miracle drug or or Miracle drugs although I I think that it potentially could be um there are some downsides of course and I I want to present both sides of this but um the research is is compelling and anecdotally I can say that I'm seeing some of this a lot of this in my practice and and I'm excited to publish we're actually working on a paper right now to publish uh uh our uh a case series on our findings specifically related to massel Activation Syndrome so stay tuned for that um specifically when we look at mental health you know again that's involving the brain but you know there may be an effect on decreas in anxiety potentially decreasing depression decreasing food noise I've certainly used these drugs in patients with histories of Eating Disorders addictive behaviors but you know like everything that we use in medicine and even in particular um with things that we use in um in Mass Activation Syndrome you know what what could uh be positive what could be could lead to a a positive result in some patients could you know lead to the opposite so I do have patients who notice that um they might feel a little more depressed with uh one drug it could be like tepati caused a little bit more of a blunted mood but but some of glutide actually didn't have that effect or or even vice versa um or both of them you know maybe maybe it's just not going to be the right drug maybe we have to wait for something better to come along so again I I wouldn't say that I wouldn't necessarily use these drug specifically for mood disorders but I do think that for a subset of patients that um where we know that the mass cells um and immune dysfunction is driving right an an inflammation is driving the mood disorder this may be a tool um that that could be potentially quite helpful um the microbiome it is really exciting there's a lot of talk about the microbiome right the microbiome is really the the bacteria um in your gut um you know ideally you want the good a good microbiome that has the right components like beaer which is a really good bacteria like you want to make sure that you have the right stuff in the gut that you don't have leaky gut and um what's interesting about these drugs is while there maybe some negative effects in the gut like slowing the gut function down the motility down the other hand there may be some positive effects on the microbiome um and um and maybe by by actually by slowing um the digestion down maybe it's allowing certain nutrients to feed the good bacteria there so there may be that positive effect um and um and so maybe and so what we're seeing is maybe there's more diversity in the gut which could lead to more weight loss and better weight control so I think that's exciting I think some of the stuff is still emerging right again sounds almost too good to be true um and and so I you know I'm G to like temper some of my excitement with you know sort of talking a little bit about the side effects because I think it's important um when you're thinking about going down this path you know to understand risk benefit um and and sometimes the benefit far out ways the side effects and if there are ways to mitigate side effects right then it's worth it but sometimes there are going to be some patients who are you not candidates for various reasons the GI symptoms are definitely the the most uh I guess concerning we would say right we um and and gener generally I would say they're they're typically worse in the beginning of treatment and worse when they're when the dosages are titrated um nausea vomiting diarrhea or constipation can be seen um I find that we can mitigate it by adjusting dosages starting slower um dosing it differently there're all kind this is where personalized medicine really comes in right this is why I love the work that I do because for each individual patient we're really thinking about how to balance all these all these risks you know there are clinics out there um I know they're being advertised I see them advertised on Instagram and social media I've had patients who have gone to these um clinics where they're basically just you know basically giving out uh these drugs with not a lot of guidance usually starting at higher dosages ramping up really quickly um and and these patients are losing tremendous muscle mass they're having tremendous side effects and trying to push through it they're not getting the guidance that they should with these drugs they're not being monitored properly um and so I really really worry about that and I really suggest that um that you have you work with a practitioner who who has experience who understands this stuff and can work with you directly okay um there can be initially um for some patients I've seen hypoglycemia so low blood sugar so managing especially early on uh because there's this satiety thing where you you feel full but your blood sugar might be falling right so understanding like when to eat and and also like dehydration could be an issue if you're not drinking enough so these are things that we always have to be you know kind of aware of there's a very very small number of people that that wind up with like a little allergic reaction or irritation at the injection site because these are mostly given injectable uh some of glutide there are formulations uh that are oral um and and while I do use those on occasion um I prefer the injectable one I think that they work a little bit better and they only you know they need to be dosed less frequently but for people who are really um uh you know needle averse like you know we we have other ways to get this into you if we if we think it's necessary um there are there's a risk of and this is a very very rare thing but you can uh get pancreatitis I've actually never seen pancreatitis and I treat you know again lots of patients um gall stones um Can Happen and what I think is happening with the gallstones is that it's not necessarily causing gall stones to be created I think a lot of these patients had gall stones didn't know it and the drug exacerbated it and so um you know some patients uh you know basically I've had one or two in my practice but but generally um if um Gall Stones become proba atic the gallbladder has to be taken out um and very rare thyroid tumors and it's a very specific type of thyroid tumor that's related to a hereditary condition and I've also never seen that related to these drugs but these are things that you talked to your your doctor about again Rapid or excessive weight loss will cause decreased muscle mass decreased muscle mass um is problematic because as you get older you want to make sure that you have enough muscle to be able to move around and and be you know be functional and prevent Falls and prevent bone loss and so we definitely monitor uh the muscle mass very closely in our CL my clinic we do a test called the body stat which measures the lean body mass the fat Mass we follow that very very closely and and I would say the majority of patients that I'm treating really don't see a loss of muscle mass because of the way that that I'm dosing it and the other things that we're doing to prevent the the loss of muscle mass like um like certain supplements exercise you know Etc um there may be um and and and I'll just say that I think it's too soon to tell yet but there may be a subset of patients who are developing a tolerance to these drugs and in that case some patients are requiring an escalation in dosage over over time um and and I have some tricks uh of the trade also uh for preventing that sometimes um cycling the drug off uh for a few weeks or a few months sometimes um playing around lowering dose increasing dose again can try to balance it so that you don't wind up needing Higher and Higher and Higher and then Max ing out the the drug um but those are things that that we have to consider and you know the drug like drug like tepati is not has not been on the market long enough to really to really know how long it's going to be until patients really develop a problem so you know what I recommend is that you know we frequently check in um and we you know track how the medication is affecting you and again figure out when the best time for an adjustment is if adjustment is needed I think a lot about um I call it micro doing I know actually a lot of people are talking about micro doing uh I've heard about it on Instagram and Facebook and and Tik Tok um I think my definition of micro doing is different from what I'm hearing out out there a lot of people are calling micro doing like you know let's say the lowest dose of tepati which is mararo let's say or Zep bound is 2. .5 millgram um and the max dose is 15 mgram uh some practitioners are saying that 2.5 is a micro do well 2.5 is the lowest dosage it's available commercially I would not call that a micro do a micro do is less than 2.5 milligrams and often can be achieved when we use compounded uh formulations and we work with a couple couple of uh pharmacies uh that are trust are trusted and have have good um uh you know tracking of of their um uh product uh and testing of their product and and with compounded uh formulations you can titrate you know very very carefully um at you know low doses uh much lower than that uh for for a lot of patients and then I mentioned that we are you know we're always talking about diet and exercise Stress Management lots of other therapies because you really want to make sure this is this is like a life this is a lifestyle treatment for a lot of patients you know there are patients that I'm treating that that don't need to lose weight but we're using it to stabilize mass cells and reduce inflammation so for those patients we're going to mic really micro do but we're going to M make sure that everything else is dialed in they're hormonally optimized they have a regimen that that is appropriate their you know their diet is as as as good as can be for their their condition and and and the hope is with these drugs that maybe all like diet and exercise and things will actually improve because they're going to feel better they're going to be able to eat better um so it's a little bit of you know uh Catch 22 right or you need to have one in line for the others to um to take hold um and we're we are you know checking body mass with a body stat test um which I think is really important and and you know the the results come out colorcoded and and it's really cool patients really really like that so I always recommend everything be personalized and then I'll end and then we'll open up for questions on uh what I'll call the natural gp1 boosting strategies now these drugs again are not are not for everyone but we have tools to boost our own production of glp1 and our own function of glp1 and so eating a diet that's higher in protein you know I would argue that a carnivore diet um may be very very helpful maybe even a keto diet um at boosting glp1 levels and increasing like satiety and decreased caloric intake um exercise boosts glp1 levels sleep um helps to balance hormones including the glp1 managing stress different types of Stress Management tools um I included lyic retraining on here because I think that that ultimately could be something that would be helpful to boost glp1 um smaller meals intermittent fasting again depending on the person these are just strategies that I have found for for patients again who maybe the the meds are not appropriate right um and you really need to stay hydrated and sometimes use use electrolytes there are a number of um of supplements that um that seem to have some glp1 activity and there's some research in the literature about um acenia which is a a type of probiotic that seems to enhance gp1 activity multistrain probiotics like my Optimum probiotic metabolic um Resveratrol beate so there are few compounds that that may also help gp1 and sometimes I'm combining these with these drugs sometimes we're starting here and seeing if we can dial everything in uh naturally without without the use of those drugs and and lastly there's an exciting drug on the horizon it's in a phase three trial right now so probably won't be released in 2020 until 2026 um I've seen it available uh from research companies uh it's a triple incron so it has three hormones the glp1 receptor Agonist the Gip receptor Agonist so that's like tepati and then a glucagon receptor Agonist and in the preliminary trials it's been shown to have um actually massive improvement over uh how tepati works and in including um improvements even better improvements in cardiovascular markers um in weight loss and things like that I'm really curious to see how this drug uh will translate to you know um inflam INF other inflammatory issues including massal Activation Syndrome um and U and this is just this is one of the studies that that was looking at these this this rat trai triple intin um and so it's a little bit Advanced but you know just showing you know uh the far-reaching effects of these different binding these different receptors and what it can do uh but decreased inflammation definitely seems to be um uh what it's going to what it's going to do and maybe even better reduced inflammation compared to the other drugs um and reduction in fatty liver maybe even better with this with this drug um so um I'll I'll end here that was a a lot of information um but I hope that it was helpful in really trying to understand you know what the buzz is about you know unfortunately I think the media has shed a you know a bad light on these drugs especially you know early on when people were taking um you know uh high doses losing a lot of weight and they started talking about like OIC face and all these things and I think that you know that's unfortunate that it kind of took that turn I think that when appropriately when monitored appropriately I really think that we you know these are incredible tools that um that uh might be helpful for for a lot of people with with very little risk if you know again if done appropriately but again nothing is is risk- free so I'll end there I think these are QR codes for my Instagram my website um and uh maybe we can um open up for for some questions um sounds great so there are about 19 qu 1920 questions so um I think that I'm afraid of butchering some of this wording so if I share this right now let me know if you can see it yeah um did the question up okay no let me let me wait maybe I should stop sharing my oh that's probably it let me stop sharing mine and then let me see the first question was um will you share the compounding pharmacies you trust um you know these are compounding pharmacies that work directly with uh Physicians so I don't I don't feel comfortable because they're not they're not pharmacies that will that any doctor can send prescriptions to they they work with specific practitioners so um yeah I I wouldn't I really um let's see what is a typical micro do dose and do they have ex acceptance that those with mcast typically react to yeah excipients exence yeah okay what was the first part of the question what is a typical micro do dose yeah so you know again I I I want to be clear like I I really can't I can't tell you what a typical one is because every patient is different um I would just say that micro doing typically is under 2.5 it could be as little as 0.1 it could be you know could be two could be you know just under the 2.5 so there's a wide range there are patients who are dosed once a week because theoretically these drugs were designed to be dosed once a week but because of the halflife of the of the drug and some patients metabolize it a little faster so like the halflife can be somewhere around four or five days um some patients we wind up dosing them every like four or five days instead of every seven days so I might reduce the total dosage and split it um so there a lot of strategies that I use um as far as excipients um it depends the the drugs that are on the market have have are are typically pretty pure um but they they have stuff in you know they have to be made with something right so um you know I wouldn't say that they're um necessarily um the ones that I think about for massel patients like microcrystaline cellulose and you know those things that are found in like capsules you're not going to see that in these injectable ones you might see them in the tablets and things that are that are somehow you know you know somewhat being marketed but but the injections are are a little bit P um the compounding pharmacies you know typically we can get them even pure um so um I think that's promising now it doesn't mean that a mass patient won't react um because with outside of the excipient issue these drugs are binding to the mass cell right and we know that that anything that binds to the mass cell could either be have a positive effect and and stabilize the mass cell but it could theoretically activate the mass cell we know that even with people who take antihistamines right you know sometimes like the antihistamines are the best thing in the world and then sometimes they're the worst thing right so so theoretically um you can see that with these drugs as well um there are a couple questions that asked about um using these medications and if you have pots or long Co yeah either both or separate yeah yeah so I think it's too soon to tell um I certainly have patients uh with both who are um taking these drugs um you know the what I think we're seeing but again I think it's still too early to comment I think that there does seem to be a reduction in some pot symptoms but I think that the that's because those patients their pots is being driven by their mass cels and if their Mass cels are being stabilized their pot symptoms are being reduced so I think I'm encouraged by that but I think it's too soon to really say that this is going to be a treatment for pots um I long covid you know in my opinion is there there are multiple reasons for long covid but one of them is um aberant Mass activation and so the same thing like if these patients really the primary issue is a dysfunctional immune system and dysfunctional mass cells then then these drugs do seem to be um you know potentially helpful um again at slow small doses dep really depends on again the patient and their profile and um the symptoms related to what you're trying to treat and then the symptoms that are that that may be even unrelated but what I think is really important and I want to emphasize this again because I said this in the beginning but I want to just drive this home patients with massal Activation Syndrome and patients in general who I see who don't have mcass the vast majority have some level of insulin resistance this is an epidemic in this world and in the Western World in general we have we have an epidemic of pre-diabetes metabolic syndrome whether it's from the food that we're eating uh maybe it's overprocessed food maybe it's uh the Plastics in our environment or the other toxins in the environment that are changing the way our metabolism works or it's chronic infections like Lyme disease that's changing the metabolism or it's mold exposure that's changing the metabolism so there's lots and lots of reasons for it but there's definitely itely an epidemic of metabolic syndrome and what I see so often is that we are we are minimizing the effect of the insulin resistance the blood sugar regulation issues on the impact it's having on lots of other symptoms and what is surprising me with with anecdotally with the patients that I'm seeing I'm using these drugs to treat certain symptoms let's say you know maybe it is weight loss maybe it is specifically for their insulin resistance and then I'm seeing these other symptoms get better and that's alerting me to the fact that maybe those symptoms actually were rooted in this insulin glucose problem and and I didn't even realize it even though I'm so tuned into this problem and have been you know working on insulin resistance for over 20 years um things like um um uh night sweats uh hot flushes things that that I used to attribute to menopause or babisia or or sometimes just massal dysfunction I have a patient I have a few patients now who have told me that you know since starting the glp1 that that symptom which was predominant is really really improved so that tells me wow that symptom may have been rooted in maybe maybe in the of the night the person gets hypoglycemic or hyperglycemic and so so I think this is exciting and I think that um we we have to start paying you know more attention to that piece of the puzzle in massel patients and and in others all right so I'll get off my Soap Box um all right do just want to do one more um yeah yeah let's see well I want to well I see one question here that you see okay yeah yeah related to um what I just said about insulin you know somebody asked uh it looks like Emily asked if you have normal insulin levels is it still beneficial for mcast patients and so again what we find is that especially in young people they may have normal insulin levels it doesn't mean the insulin is working properly and it could be that the insulin you know in the bloodstream you you draw it with blood work and it looks normal but maybe the cell is resistant to it and so it's actually not working super well and and there may be fluctuations in the blood sugar and in that case that could be very beneficial to mcast patients in addition um you know again I said that these drugs bind uh massed cells at the glp1 receptor and and maybe a St have a stabilizing effect independent of the insulin effects and so in that way it has the potential uh to do that what we don't know yet because we just don't have the number of patients who have been treat you know enough patients that have been treated is we don't know whether uh patients without any any insulin resistance or any blood sugar issue is going to respond to these these drugs now again I think that's very very few patients who don't have a true problem with their insulin very very few but especially massel patients because we know there's a link between um glucose metabolism and and massel Activation Syndrome um but but it would be interesting to study that if we could find patients who had no insulin problem no glucose problem and see what this effect the effect of these drugs are um should I do one more and then we'll yeah did you see a special one that yeah so uh let's see um okay so uh somebody asked about taking a gut motility supplement for sibo and would it interfere with the reduced gastric emptying aspect of these drugs like mararo um and you know what I would say is that excuse me the majority of supplements on the on the market are not going to be truly strong enough to overcome completely the effects of these drugs on on the gastric emptying so I would think that that would be fine and in some ways maybe helpful for patients where sure you want a little bit delayed gastri emptying you know for the benefit of the drug but you don't want too much because too much when when you really slow the gut down that could increase the risk of sibo that is a potential problem so my thought is that yeah like if you're if you're on some stuff to prevent sibo and you take micro doing of of these drugs maybe you wind up with a neutral effect on the on the gut but then you have actually a positive effect on on inflammation in mass cells and and other things because even though the literature says that the gastric emptying process is the delay in it is really what is helping weight loss I'm not convinced of that I don't think it's just that you the food moves slower and that's why people are Fuller I think that it's more what's happening in the level of the brain uh where the brain signaling is changing so my thought is if the gastric emptying actually improves there are less side effects as long as this drug can bind to where it needs to bind to have you know to have the effects we're looking for so anyway so that's just my thoughts for you know for now um okay great well thank you Dr deny and we will have an email out tomorrow morning with the replay and the PowerPoint as well just would can I include that as well yeah yeah okay great because I think it' be really helpful for everyone to have their own set of it um yeah and I think that was great and then we'll probably have another one um hopefully early 2025 um yeah I look forward to it okay great well thanks everyone for coming everyone I really appreciate you you being here and stay tuned for for the next one good night bye e e e