69: GLP-1s Are Not Just for Weight Loss - The Smarter Microdosing Strategy for Metabolism Muscle and Long Term Health with McCall McPherson

Foreign. So today we are talking all things glp. We are doing an Ask Me Anything where you guys submitted any and all questions you wanted answered on this topic on my Instagram story. So if you don't follow me there, please do. And we're going to get them all answered. These are some of my most popular episodes. You guys had some incredible questions. We'll be talking about all things from microdosing to my favorite GLP to side effects to longevity to thyroid cancer, how to come off successfully, do we need to be on them long term? All the things. So let's dig in. So talk about what is a glp? So a GLP is a glucagon, like peptide and that our body makes on our own. And so what we are doing is we are tapping into a pre existing mechanism in our physiology and we are increasing the amount of that peptide and increasing the amount of time our body is exposed to it. Because normally GLP endogenous peptides come and go pretty quickly. But. But fascinating stuff. These medications first came around about 20, 25 years ago for the treatment of diabetes. And while they were being used in diabetics, we noticed pretty quickly that people were losing weight. And that's usually a pretty difficult thing for people who have diabetes to do. So we repurposed them several years ago for weight loss. And these are medications like Manjaro, Wegovy, Zepp Bound, semaglutide, tirzepatide, ozempic, etc. Okay, so that's kind of the basics. What these medications do is in our physiology, they do a lot more than simply reduce the amount of food that we eat. People think, oh well, you only lose weight because you eat less. And honestly that's actually not true at all. So we do in fact eat less. Part of the mechanism of these medications is to slow down our gastrointestinal tract, making us fuller, longer, making us eat less quantities of food. They also impact so many other mechanisms in our physiology, things like, you know, cravings. They also reduce the circulating blood sugar that we have because they promote the release of insulin, reducing blood sugar so that when there's less sugar circulating around in our bloodstream, we are less prone to deposit fat. Okay, so those are some of the mechanisms of action. What I want people to understand is these meds work even if in fact people don't reduce fat, their calories. Even if they eat the same, people can still lose weight compared to when they ate that exact same way off of these medications. So let's do some rapid fire. You're going to see me looking down, you're going to see me glancing at my notes, et cetera. Is semaglutide or tirzepatide better for inflammation and weight loss or are they similar? Is there one I prefer? So if you guys have been living under a rock or maybe you don't follow my content. GLPs are the most potent and powerful thing I have ever seen from for inflammation. Not only have I seen that in my personal practice with so many patients for years now, I've also found it in research. I found four pathways by which GLPs reduce inflammation. They can reduce the release and impact the inflammatory response, interleukin 6 cytokines, etc in our bloodstream. But they also increase antioxidant activity which, which combats inflammation. So they 1 reduce inflammation and the effects of inflammation on our body and 2 increase anti inflammatory effects. So it seems to be a win, win, win. In my experience with my patients I find equal anti inflammatory benefits between semaglutide and tirzepatide. So that leaves the question which one is my favorite? So this will surprise people, honestly for the vast majority of people when they are on a micro dosing schedule and we'll talk about what that means later, but that means smaller amounts of medication, not the standardized approach, increasing every four weeks, et cetera. I find most people do best on semaglutide. The biggest worry with these meds is losing too much weight too quickly, not eating enough food, not fueling your body. Okay. Undereating, micronutrient depletion, protein insufficiency leads to side effects. Rapid weight loss is pretty much the driving factor of almost every side effect that you hear in the media. So we do not want you to do that. And that's kind of hard to do if you're using tirzepatide. To get a small enough dose where you don't get an overly suppressed appetite is challenging with tirzepatite. So for the vast majority of people, I want them to start on semaglutide. Beyond that, if they have a lot of weight to lose, this is especially useful because you build up tolerance to the medication over time. And if they need to lose weight over three, four, five years, we want that medication to be effective as long as possible. So one of the keys in doing that is slowing the dose increases of course, but once they run out of efficacy with semaglutide, they can then move to tirzepatide and have an entire other wave of efficacy. Most people Never need to do that. But again, our main goal is protecting and prioritizing you not being having an appetite that is so low that you can't get in enough nutrients and calories. Another common question, another common question that you all had was about the duration of time you need to be on these meds. So one question is, can we really be on them forever? Should we really be on them forever? Do we have to be on them forever? And this is individualized, right? Like this is something you have to figure out with your specific clinician. Absolutely. But here's our shtick at modern thyroid clinic and modern weight loss. Basically, the vast majority of people in our experience do not need to be on these meds forever. Now, research says, yes, these, these manufacturers of these medications have made them for people to be on forever. I think, you know, there is certainly some benefit to them in doing that. But also, these meds that were originally studied, they were studied for diabetics that of course need to be on them forever. Right? So what we work on in our weight loss programs is improving metabolic funct, reducing metabolic dysfunction that leads people to get in this situation in the first place, which is extremely common with people with hypothyroidism. So they lose their metabolic sensitivity, their insulin increases, their leptin or fat storage hormone increases, and then they just inappropriately store fat and can no longer lose weight with appropriate amounts of effort. So when we start to unravel that with the glp, not only do we see weight loss, but we see more reductions in insulin over time, managing blood sugar better and better, meaning this person needs less insulin to maintain appropriate levels of blood sugar. We also see over time, leptin resistance improvement. When you have leptin resistance, you tend to not feel satiated after you eat. You tend to inappropriately store fat. And it's another hallmark of people with metabolic dysfunction. So if we can reduce insulin back to sensitive levels, if we can reduce leptin, hold blood sugar at really good levels, with all of these things tightly controlled, most people can come off of these meds and maintain their weight loss with appropriate amounts of effort. Now, when studies are done for looking at if people need these meds forever, right. Let's say a person with hypothyroidism for 30 years goes on these meds, they have a poor lifestyle, they don't eat great, they're in the study. So they clean up their lifestyle a little bit, they eat better, they're on these medications, but they still have hypothyroidism, they still have Insulin resistance, they still have leptin resistance, and then they come off of these meds. Guess what? These people are not going to maintain their weight loss. They're going to gain weight, especially if they don't maintain proper lifestyle. That looks quite different in an environment where all of these variables are controlled, understood, been collected, the data has been analyzed. We come up with a plan together, very different story. Ways to maximize the ability to successfully come off of these meds. Number one, you need to work with someone with that end goal in mind. You need to work with someone who's gathering all the data. The one thing I actually do not publicly share is the numbers that we are looking for in our weight loss programs that we find allow people to come off of their GLPs. That is literally the only piece of information I hold back from you all because it's still kind of pretty much ours and novel and proprietary. But you want to find someone that has that goal in mind. Some other ways are slowly tapering off. Continuing on a microdose or sometimes we transition people off of a GLP onto metformin to help further solidify their metabolic improvement and just maintain really optimal blood sugar because that is key. Blood sugar, insulin, leptin are absolutely key to maintain. Now, who wants to be on these meds forever? Generally for us, it's inflamed people. It's people who have struggled with inflammation their entire lives. They revolve their whole existence around it. They work very hard to improve it, but they never can improve it to the degree that they feel great. And if you come off of these meds and you know, you're really genetically based inflammatory kind of issues, meaning we're not going to go in and change your genes. Right? So inevitably the inflammation is going to come back. If you come off of your inflammation is going to come back. Now the second category of those people are, let's say obese people who have a lot of central adiposity weight around their midsection. They have really high insulin. Insulin's an inflammatory hormone. So if we can get rid of all of that, their inflammation could carry on and be much less, but not that of a genetically predispositioned person for inflammation. So kind of keep that in mind as well. Definitely the people that we find stay on it are like, wow, this has changed my whole life for an inflammatory, inflammatory standpoint, et cetera. Let's talk about going on GLPs, pregnant, pre pregnancy planning, breastfeeding. So GLPs very much improve people's fertility in a lot of different ways. I do think they will be a future treatment for infertility, but medicine generally does not like to test on pregnant women, breastfeeding women, et cetera. Why? Because, gosh, imagine the outcomes if it doesn't go well. Right. We never want to compromise the health of someone's baby, so we generally just stay away from testing. So there has been no formal testing on safety for pregnant or breastfeeding women with GLPs. The formal recommendation is to stop GLPs for women two months before they actively pregnancy, attempt, or, you know, try to conceive. It's actually three months for men. So men should stop GLPs three months before trying to conceive with their partner. You know, I think a lot of people have gotten pregnant on GLPs because they were historically infertile, and then, wow, all of a sudden they were fertile and they had no idea got pregnant. When looking at the data that came out a few months ago on outcomes for pregnant women that took glps unknowingly, the data was pretty clear that there weren't any effects. But that still has not been formally studied to go and say, hey, these are safe. These are effective for breastfeeding or pregnancy. You know, formally speaking, people should not be taking them while breastfeeding or while pregnant. Let's talk about efficacy of these meds. Do they work for everyone? Should we take breaks to promote efficacy, et cetera? So what I find is a couple nuances. Number one, let's say someone comes into modern thyroid clinic as a new thyroid patient, and they've never been treated for thyroid, or they're not being treated well. Maybe they're on levothyroxine or something, and they want to start a GLP at the same time. People that start those two things at the same time have a slower weight loss shift as compared to someone who maybe has been our patient for five years and their thyroid's perfect, but they still haven't been able to lose weight. We start them on a glp, those people tend to lose weight more quickly. Why? Because their metabolism, the reason that disrupted their metabolism in the first place, has been largely addressed. Now we just need to unravel the metabolic dysfunction. Whereas in the first case, that's a little different. Right? So there is nuances to how quickly people lose weight. Also, another pattern I found is if someone comes in with crazy high insulin, really high blood sugar, we have to use a glp, start to bring all of that down before it begins, the weight loss part of everything. So, you know, not Everyone is going to lose weight at the same pace and the same rate. The farther you have to go up front to get to a better metabolic function, the slower your weight loss is going to be initially. And then the other thing I like to remind people, someone in the comments says, I haven't lost any weight and I'm in month three. Three. Well, here's the thing. Even on standard doses of the medication, which in my opinion are wildly, irresponsibly too high, generally people don't start losing weight till close to the three month mark. So with microdosing, with tailored dosing, with slower amounts being introduced over time, you're going to lose weight even more slowly. And it's really important that you set your expectations that way because honestly, these meds work for, I would say 98% of people in my experience, but we don't want them to work as well as you're seeing in the media that you're hearing from your friends. We don't want people losing weight that quickly. So we need to shift our expectations and be okay with a slower timeline. You know, someone asked about, do people stay in the shots for life? What about switching to the oral pills? So I haven't used the Wegovy pills with my patients that are just coming out now. I have tried compounded oral forms, sublingual forms of all kinds, like every possible combination. We could never get them to be effective enough to even offer. So I don't know. The jury's still out. I'm curious because the study looks really promising for the oral Wegovy, but we'll have to see. One other strategy for keeping them efficacious, keeping them working is to take breaks. And we do that in our weight loss programs. So oftentimes we'll offer a six to eight week break to allow people to reset a little bit. Usually when they restart. Weight loss is a little slower initially, but it can definitely, if you have a lot of weight to lose over a long period of time, it can help to maintain the effect of these medications without building up too much of a tolerance for them. Have I ever seen GLP options not work for people with weight loss? I think maybe one or two times I have seen it. It's rare, but very, very rare can happen though. Someone asked what GOP Oprah's on? I do not know. And then let's talk about microdosing. Microdosing. We have been doing microdosing on our patients since before this was a word that was associated with GLPs. So we started out with standard dosing, gosh, probably close to four, four years now. And quickly realized these people were having a fair amount of side effects. They weren't getting enough food, they were having a hard time eating. And this was not a winning game plan. So we started reducing doses over time and then tailoring doses, meaning not everyone gets the same one size fits all approach. Right. We try to keep people on the lowest dose possible that's still effective. So a microdose is anything less than the lowest available dose. Usually. To give you some idea, we generally start people at a quarter to an eighth of the lowest available dose. So we're talking tiny, tiny, tiny amounts of medication, y'. All. But honestly, it works incredibly well. I went from writing multiple Zofran anti nausea prescriptions every day for patients in our program to writing, you know, one in the last two years. It's just wildly, wildly different. So pretty interesting stuff. Will microdose cause the same muscle loss as normal dosing? No. So the, the benefits of microdosing are, again, you know, just to reiterate, the vast majority of side effects that you all hear about in the media are from rapid weight loss, muscle loss, collagen loss, hair loss, gallbladder issues, pancreatic issues, GI based issues, vision loss. Pretty much all of these issues can be sourced back to rapid weight loss, causing subsequent sequela or issues in your body thereafter. Microdosing allows for slow weight loss while maintaining enough protein, while maintaining enough micronutrients. So what happens in that one? You don't lose a bunch of muscle, right. Because your body's not looking in this emergency state for, oh my God, I don't have any access to food. What can I burn for fuel? Okay, I'm going to take some of her muscle mass. That's not what happens. You get to preserve that because you're eating enough food to burn as fuel and then can also additionally burn fat stores. Okay, hair, think about hair. I got so many questions about hair loss. The vast majority of cases, I would estimate 95% plus of hair loss is due to either rapid weight loss, triggering, going into the phase of hair loss where all of your hair gets lost at the same time. Teflon effluvium, where instead of cycling hair loss little bits at a time over weeks and weeks and weeks, it all just happens simultaneously. So you lose a lot of your hair. The other way that we see a lot of hair loss frequently with GLP patients we don't really see anymore. But out in the wild is again, your body's Looking for sources of fuel. It doesn't have enough food, it doesn't have enough fat, so it's pulling from your hair. And so your. Your body has to prioritize. What are we going to build, what are we going to grow? It's not going to be your hair when you don't have enough fuel. Microdosing avoids largely all of that. I've seen one study that kind of painted a picture that there could be an independent mechanism of hair loss that could be occurring with glp. It is so rare. I've. I've actually not seen that firsthand myself. What can you do to protect yourself from hair loss? Microdose only increase your doses. When you absolutely need to take collagen, take neutrophil or even better, the true Niagen hair skin health. One that has, you know, nad to give you some energy while you're on a glp, plus hair loss, plus collagen and hyaluronic acid support. So get those. You could consider taking an oral microdose of minoxidil, like 1.25 mg, use topical minoxidil, which is Rogaine. But you can do that orally, and it's much, much more effective. You know, red light on your scalp, microneedling on your scalp, those sorts of things. But basically, you want to get enough protein, micronutrients, etc. As the absolute necessary thing. What can be used for hair loss? Okay, Is microducing tirzepatide causing hair shedding? Very rarely. Again, y' all take your. Your supplements. You could always do things like minoxidil, etc. Talk about some positives of GLPs, because this is where I really get excited. Okay, well, let's talk first about this concept of cancer, especially thyroid cancer, because I still get this question, and I've talked about this so very long, yet, you know, here we are still talking about the same thing. The black box warning on GLPs for thyroid cancer came because during rat studies, animal model studies, there was an increase incidence in medullary thyroid carcinoma. A couple things that I feel like are important to delineate from this study. I think in the future, the black box warning will be removed kind of like it was with testosterone. But it took decades to make that happen. In these rat studies, rats were given 20 to 100 times the human equivalent dose of GLPs. And it just so happens also that rats have a lot of GLP receptors on their thyroid gland. Okay, Making them more vulnerable to this when Looking at human studies, even intercontinental human studies, meaning looking at various continents and analyzing data, there has not been shown in some of the largest trials to be a statistically significant risk for medullary thyroid carcinoma or multiple endocrine neoplasia. Now, if I had a patient with a history of MTC or men, those are those two cancers I just mentioned. I would not put a person on a GLP if they've had a history of papillary thyroid carcinoma. These other forms, they're post thyroida 10 years ago. There is no research showing increased risk for other forms of thyroid cancer, certainly at all. In fact, one study showed there's a higher risk of insulin causing issues with thyroid cancer or correlating with issues with thyroid cancer than glp. And insulin does not carry any risk whatsoever for thyroid cancer. So very, very important that you all have the facts. So let's talk about some more facts with cancer. And then I want to talk about heart disease too, and just risks about death in general. So we talked about how they don't cause thyroid cancer. But what I want you guys to know about is the story doesn't really end there. In fact, GLP have been looked at in many studies and shown a risk reduction for cancer. So I'm going to run through some of these that I found. A, a relative risk reduction in breast cancer of 13%, lung cancer 19%, prostate cancer, 17%, colorectal cancer, 16%, pancreatic cancer 6%. That's another one that you guys keep hearing. Oh, well, they'll increase your chance of pancreatic cancer. Well, actually they've reduced it by 6%. And rapid weight loss can lead to gallbladder issues, which can lead to pancreas issues which can lead to pancreatitis, which can lead to an increased risk in cancer. It's not the glp. It's rapid, rapid weight loss. Okay, so let's talk about another piece of data. So GLPs improve cancer survivor survival in people with a history of cancer. So the use of GLPs was associated with a significantly lower all cause mortality in cancer survivors and no increase in recurrence risk. There's also benefits about GLPs that impact innumerable aspects of our health, y'. All. I've curated some from a study that looked at benefits and risks of GLP across 175 health outcomes. This was published in JAMA and it showed a risk reduction of Alzheimer's of about 12%, schizophrenia psychosis of about 17, 18%, bulimia 18%. That's right, you heard me. I think these meds will be the future of disordered eating and eating disorder treatment. 10% reduction in suicidal ideation and self harm. 15% reduction in cardiovascular events. But I want to go deeper with the cardiovascular events because I think we all get very afraid of cancer. We're sort of in our society, we are primed to fear cancer, but we do not think about heart disease enough. Heart disease kills more people every year than all forms of cancer combined. I want to repeat that. Heart disease kills more people every year than all forms of cancer combined. We need to be protecting ourself against heart disease. And in my opinion there is nothing more protective against heart disease and death related to heart disease compared to a glp. So let's, let's talk about some stats here across various trials like the MACE trial leader and select. My first topic is MACE. Major adverse cardiovascular events. There was a reduction in 12 to 27% of MACE across all of these studies. So different studies shows different numbers. Heart attack that was non fatal, a 25% reduction. Stroke, 16 to 39% reduction depending on the study. Cardiovascular death, 13 to 22% reduction. Then what's really fascinating y' all is there was a reduction in all cause mortality, meaning your chance of dying on a GLP. You're less likely to die by 15 to 20% period, full stop. Doesn't matter if you get hit by a bus. Cancer, cardiovascular disease, the flu, whatever it is, you are 15 to 20% less likely to die by anything if you're on a glp. So what's so fascinating to me is everyone is talking constantly about the risks of these medications. Medications will change so many aspects of medicine forever, permanently. Let's talk just briefly too on how they relate to thyroid. Okay, so couple patterns that I think you guys would think are interesting. Number one, for the first few years of our programs we had everyone go get a thyroid ultrasound every three months because I'm crazy and I wanted to know if these meds were causing nodules, growth, et cetera. We saw nothing. We don't require our people to do that anymore. But we do give them the option to and we send in an order for them. So should they so choose. We do see a couple things. Someone asked about absorption of their thyroid medication with slower gastric emptying. I have seen that on rare occasions. It's definitely the exception, not the rule. But I do think you can be a little more cautious if you're on these meds and on thyroid medication, especially in the afternoon. Our patients dose in the morning. And in the late afternoon, when you eat food, try to spread out more time before you take your thyroid meds. I usually make people wait an hour. I would say maybe wait an hour and a half to two hours after you eat to take them in the morning. It's really easy because you can take them first thing and then wait to eat. So kind of keep that in mind. Couple other nuances that you guys would probably think are interesting. Number one, it is undeniable that these medications reduce Hashimoto's antibodies full stop, period. It is almost ubiquitous. I see it all the time. It is incredibly rare that someone comes back into clinic and their antibodies haven't reduced on a glp. So definitely reverses Hashimoto's. Let's talk about the need for thyroid meds. And I know I'm talking so quickly. Sorry, guys. I'm trying to cram in a lot into a little bit of time. But when people first go on these meds, I notice an uptick in hormone transport actions, meaning they start to utilize their hormones more, kind of excrete them more quickly. So it's not uncommon for me to initially need to increase someone's thyroid medication over time. As people lose weight, you need thyroid med reductions. Okay? A lot of thyroid medication dosage depends on weight. So as you lose weight, you need less thyroid hormone. And so every 10 to 15 pounds, you should be getting your thyroid checked, making sure we don't need to reduce your dose. And a lot of people maintain that dose reduction after they stop meds. And a lot of people, when they stop GLPs, they need a third further dose reduction because of that same mechanism that tends to increase the rate at which you use your thyroid medication. That goes away when you stop a glp, so you tend to have more hormones. So in the end, you could end up on less medication than you would have thought. Let me just breeze through these. Someone asked about the effects of GLPs on addiction. Substance only. Or does it have behavioral addictions, too? Absolutely. Addictions, compulsions, all of it. Again, these meds are going to be used for so much in the future, y'. All. But no, all of that can improve with glp. My favorite kind of exercise on GLP is weight training. Strength training. Strength train, Strength train. Okay? You want to build muscle, increase your basal metabolic rate. You want to do it slowly so that in between sets, you allow your heart rate to come back down. Do not tax your adrenals so much. I also love walking. Okay. I don't love cardio. That's high intensity. I don't love HIIT. I don't love CrossFit. For people on GLPS, we want to increase your muscle mass but not tax your system so much when it could already be a bit stressed. Okay, well y', all, I think I covered so darn much. I'm excited to share this episode with you. I hope you enjoyed it. Please share it with a friend that might also benefit from the information. But y', all, please, please, please. If you do not mind the generously giving us a review on your favorite podcast platform, it would mean the world to me. It certainly helps us on our end. Downloading sharing with a friend also helps us. We would love your opinion and your review if you can take a few minutes to share.