What We Got Wrong About GLP-1s (And What's Right) | Dr. Tyna Moore

21:01Dr. Mark Hyman:So it was purely the food. You know, sort of like to paraphrase Bill Clinton, it's the food stupid. So I don't know how much extra advantage there is to GLP-1s. It's certainly, it's sort of an assist, I would say. It's a support for people who struggle. It can help break a cycle of addiction, break a cycle of various things that happen metabolically that are hard to break. But is there something special and unique about these that are over and above just the weight loss that you see? Because you're right. If you improve metabolic health, you improve cardiovascular risk, dementia risk, hormonal health, you know, immune health, inflammation levels, obviously your risk of, you know, diabetes, all these things get better.

21:39Dr. Mark Hyman:Mood gets better. Brain health gets better. You know, psychiatric conditions get better. And it's not like some magic kind of thing. So I'm just wondering your perspective on that. I think they do. And I'll give you a couple examples. Well, for one, we know they land on immune cells. There's receptors on our immune cells and they land on mast cells in particular. So they can help. I've seen significant improvements in folks with mast cell activation syndrome. And for those who are listening, that is essentially a syndrome where you get very allergic to everything and you have high histamine levels.

22:09Yes, and it's miserable. These folks can't take anything. And I've got colleagues using 1 100th or 1 50th of the starting dose, tiny, tiny little doses of trisepatide. And suddenly the patient's inflammation will regulate out so then they can actually get to work and start utilizing different therapeutics and modalities, whereas before that would flare the patient. These patients were very sensitive. SERS patients, Lyme patients. I'm watching doctors utilize these at very small doses just to kind of stabilize the immune system. Tons of reports from people. I've gotten thousands and thousands of messages over the past few years of people saying, I was able to go off my antidepressants within a few weeks.

22:49I stopped gambling. A study just came out, like I just saw it this morning when I was getting ready. This is crazy, Mark. They compared folks who were alcoholics and other drugs utilizing who had been on GLP-1s, and they found that whilst on the GLP-1, and we know this because there's some data coming out now around alcohol, cessation, smoking, and we talked about that a little bit last time. they not only had significant improvement when they were on the GLP-1, but the results lasted up to like 30 or 40%. I think it was like 39 % improvement even after discontinuation of the GLP-1. So it's changing the architecture in our brain somehow.

23:32It's playing on the dopamine pathways. And I don't know, depending on the dose, I don't know how good or bad that is, right? I mean, that's a whole other dilemma. But I do think there's several different mechanisms happening. This is another crazy one I just have to throw out there. A lot of people have come into my DMs. I'm in a really unique position because I have a lot of followers that message me about this. And I mean, hundreds of thousands of followers across platforms. And a lot of people are having their disordered eating disappear. These are bulimics and anorexics and orthorexics. and it completely, at a microdose or at whatever their dose is, it completely obliterates the actual under eating.

24:14It's not making them under eat. And then cancer. I've had a few people who are using it with cancer. Doctors, oncologists are now using it with patients in conjunction with their cancer therapy and approving it, which I thought was nuts and exciting. These folks are having better outcomes across the board. Their, their quality of life is better. Their mood is better and they, it's not completely crushed. In some cases it might be depending on the dose, but it's not completely crushing their appetite. In fact, it's helping them eat. So I think it, I think it does something in the brain and plays both sides of that.

24:46I don't, I don't know how, but.

24:48Dr. Mark Hyman:So it seems to have, it has unique brain benefits around addiction, around obviously after regulation, but also. Immune benefits. Immune benefits. So these immune benefits are fascinating to me. Do we, do we understand the mechanism yet of how these work on the immune level because we know inflammation generally goes down as your metabolic health gets better, right? Your metabolic health determines your visceral fat is all inflammatory. So is it just that or is there something else going on? I don't know. I don't know. I just know that they land on mast cells. I was trying to get every single person I knew who had MCAS to try a microdose.

25:20I was like, please just tell me what happens. Just take the microdose and tell me what happens. And everyone who did, miraculous. The responses I got from people were like, I can't believe I waited. This has changed everything for me. And they can tolerate the world now. They can go through the world and live like normal people. They're still watching what they eat, but they can have a glass of wine and not have their whole life derail. They can function. They can eat fermented foods again. Here's the important part is they can eat fermented foods again, and they can eat so many of these high histamine foods that these folks have to avoid usually are the same foods that bring us optimal health.

25:55Dr. Mark Hyman:And these are on the micro doses, right? Yeah, or depends maybe on a regular dose. And that's the other part. A study came out last year showing genetic differences in people. So some people have very different responses to GLP-1s depending on their genetics. Some don't respond at all. That's why there's non-responders. Some get more nausea than others. And so that kind of proves what I was getting at in 2024 is like, I think we're all really different. And I think we have to really look at different dosing because some folks are not responding to semaglutide and terzepatide helps them. It changes their life like night and day.

26:28The difference is some people don't respond at all. It's kind of all over the board. And so I think dosing is very individualized still. What might be low for one person might be a regular dose for someone else. Kind of depends. And it does depend on how they're eating and it does depend on their overall metabolic health. I will give you that. And it does depend on how much they're hitting the gym. But that said, I still think this is a tool that is in conjunction with and not instead of. You've got to do everything you said. You have to do all the lifestyle pieces too. And that part, I will say, people, I've noticed with my patients.

27:02You want to skip that bit. Well, you know, they start out strong. They start out with good intentions. but the minute that GLP-1 kicks in and it's, I call it kind of the ultimate F around and find out peptide because it does clear up so much of the inflammatory noise for some people that they're like, I can eat gluten again. I can handle carbs again. I can do all these things again. And eventually it, there's a concept in medicine, you know this, but for the audience, it's called tachyphylaxis and it's where you acclimate to the drug.

27:31Dr. Mark Hyman:Yeah. You acclimate very quickly to the drug and this is known for that. And so all of a sudden they find out and it comes back to haunt them. So it's not a get out of jail free card and you still have to do all the lifestyle pieces. And eventually that microdose will stop working if you keep effing around and find out. Um, but I think that as a tool for those folks who are doing the things, or maybe those folks are not doing the things and this is the thing, keeping them alive. I don't know. It's, it's a lot of different applications. Maybe we can back up a little bit, um, because we kind of jumped ahead But I think maybe for people listening who don't know exactly what peptides are or exactly how these new drugs, these GLP-1 drugs work, help us understand it.

28:12Dr. Mark Hyman:Because most people don't realize that these are things that our bodies normally make, but we're either low in them for different reasons, like you said, like statin use, or maybe there's other reasons. And how do they actually, how do they do their job? So GLP-1 is a peptide that our body makes. It was first discovered or a version of it was first discovered in Gila. Well, I shouldn't say that. I looked up the history. It was discovered in humans, but then it was rediscovered in Gila lizard venom. I live in the high Sonoran desert. So we have Gila monsters out here. I've seen them. They're pink.

28:47They're very pretty. But what they found was the Gila monster only has to eat a couple times a year. And so they isolated this Xenadin 4 out of its venom and said, hey, this is the thing that keeps it from needing to eat. And that is not what GLP-1s are. They then looked at humans and said, oh, humans have a similar mechanism. And so for everyone saying it's, have you heard that, Mark, that going around that it's derived from, oh, Zempic is derived from blizzard venom. I haven't heard that now. You're blissfully unaware of the nonsense on the internet. I started just blocking people who send me those videos.

29:22I'm like, I can't, I can't even do this.

29:23Dr. Mark Hyman:Yeah, I try not to pay attention to the noise and just stay on the signal. Stay on the mission. Stay on mission. We make it in our guts and we make it in our brains and it goes throughout the body and does different things. And it is definitely, from what we understand, I think we're just beginning to understand all of these leptin grill. And I think we have a really rudimentary understanding of them. But it is in that family. And like I said, it plays on the gut. It plays on the brain. It plays on appetite. It plays on your insulin. And it helps your insulin signaling improve. It helps it signal when it's supposed to signal more appropriately.

29:56The drug itself is just a peptide. A peptide is a string of amino acids. Strings of peptides are proteins at fifth grade level biology. And so it's a very simple system. And then the pharmaceutical companies have tweaked the molecule or the string of amino acids, the peptide, to have a longer half-life because our naturally occurring GLP-1 is in and out of our system very quickly. And then this one is in and out of our system in five to seven days.

30:23Dr. Mark Hyman:So they tweaked it a little bit. It's not exactly bioidentical. is a little tweet. It's pretty close. But yeah, I think it's like 93 or 94 % bioidentical semaglutide. That's just pure GLP one semaglutide. That would be Ozempic and Monjor. I'm sorry, Ozempic and Wagovi. Same, same medication, same pharmaceutical company, one's FDA approved for weight loss, one's FDA approved for type two diabetes. And then we have trisepitide, which is a dual agonist. That's GLP one with GIP. GIP has different mechanisms inside of our body that help regulate our blood sugar. And, you know, supposedly the GIP should be helping sequester and get fat oxidation going better.

31:04And that would be terzepatide. And that is Monjaro and ZepBound. Again, same company, same molecule, just two different FDA approvals. And then we have the new kid on the block, which is retatrutide. Oh, let me back up. Terzepatide is like I think one to five I might be off a little bit from but what I've researched it's one to five ratio of GLP-1 to GIP so when people say oh look at all these benefits in the studies of GLP-1 in particular not the medication terzepatide but when they just studied GLP-1 over the past many decades that there's less GLP-1 in terzepatide overall than there is to GIP the ratio is different.

31:45And then with retitrutide, that's a triple agonist and it has glucagon agonism, which they thought might help preserve muscle mass. I don't think that's coming out to show, but in the studies, but it has, that medication has tremendous weight loss happening with it and a lot of fatty liver, a lot of impact on the fatty liver, which is really cool. But that has very, very little GLP-1 in it overall. It's mainly, mainly GIP and glucagon. So.

32:15Dr. Mark Hyman:But that's not really available yet, right? No, that is in phase three trials. I just saw this morning that they're hoping for, I think, 2027, and they're trying to get it classified as a biologic and not what it would normally be. So then it can't be compounded and they can really throw the hammer down and they can really jack the price up. But I've seen people selling it on the gray market. Yeah. The gray market is like the wild west. So you can get it, but you don't know what you're getting, you know, if it's safely produced, if it's the effective dose, if it's got some of the contaminants in it, you don't have any idea.

32:51Dr. Mark Hyman:I think that's another conversation we'll have in a minute, but you know, these things are really quite interesting. I think that, that, you know, I kind of want to just, just, just step back a bit. Cause I think people have heard about a lot of side effects. And I, and I did a bunch of research recently about this. And I think your weight loss, muscle loss concept, it makes sense to me. And I actually had that thought that actually, you know, the weight loss is the thing without exercise that drives the muscle loss. If you don't do strength training and you don't do protein. The other, the other thing is, is the weight regain.

33:28Dr. Mark Hyman:Cause when people stop it, there's a lot of data from the step one trial and others that people who lost a lot of weight within one year of stopping, they regain two-thirds of the weight. And also, all the cardiometabolic improvements reverted toward the baseline. Same thing happened with the surmount four trial with terseptide. So, you know, they're good while you take them, but then there's a sort of ozempic rebound phenomenon that happens. And what do you make of that? Yeah, I completely agree. And to your defense, in that study that came out last Last year, in November of 2025, they looked at two separate groups.

34:04They looked at the GLP-1 group, and then they looked at lifestyle group. And the lifestyle group was not taking a GLP-1. And when the weight regain happened for all of them, I think keeping weight off, I said this on your last episode that I was on, and people came at me and got really mad. The weight loss part is actually the easier part. It's the keeping the weight off that is so significantly harder. And I think what, like five, 10 % of people who go through a weight loss journey will actually keep it off. It just keeps coming back. The fat cells have memory and the, and the body has a set weight and it all wants to come back.

34:37And like you said, when you get lighter, so you lose the fat, you lose the leptin, the leptin and the ghrelin are playing with your appetite and it is very, very difficult to keep the weight off. And your set point stays where it wants to stay depending on how long you've been at that weight. So the GLP-1 group, the terzepatide and semaglutide actually had faster weight rebound. The newer incretin medications had faster weight rebound than even some of the older ones, which tells me the fancier the peptide, the fancier the medication, the faster the weight regained. The faster you lose it, the faster weight regained.

35:13But I think that's, we know that with weight loss anyway, right? That was before there were GLP-1s. We knew that. And so going on a slow and low journey, doing it right, utilizing that this opportunity as a window of opportunity to completely modify lifestyle and do all the things I think is obviously the best route. And then knowing that you probably should be and I think doctors are getting hip to this. There has to be a titration strategy. And we might be looking at some people as lifers. There's going to be a subset of people that are on this for the rest of their life for sure. and there's other people that may be able to come off.

35:49And I think we don't have enough studies. They're looking finally at studies of GLP-1 and strength training. We don't have any good studies on that yet. But when you, there's a study out from a few years back, same group that's doing the current studies, utilizing strength training during a weight loss journey leads to appreciable weight loss retention.

36:06Dr. Mark Hyman:Yeah, it's quite amazing. I have a number of patients like that. I've had, they've really struggled with weight. I got them on low dose GLP-1s and then I said, look, you have to be in the gym. You have to do DEXA scans every month. You have to like eat this protein and they do it. I mean, actually they're doing it. And it's quite amazing to see the muscle, the weight will go down, but they'll actually increase their muscle and they'll lose even more fat. And so you, if you lose, you know, 10 pounds of fat and you gain five pounds of muscle, your weight loss is only five pounds, but you've changed your body composition.

36:37Dr. Mark Hyman:So it's quite interesting to see that that's possible even with these compounds. Yeah. That's really the question I'm sort of noodling with is are these lifelong drugs uh they're are they safe long term you know the cost I think is coming down which is good but it's still a lot and I don't think insurance still pays for most most of it except you're diabetic and so it's really you know we're kind of in this gray zone of not really knowing what happens if people take these for 10 15 20 years right and and and do people need to take them if if they want to sustain the metabolic benefits and not kind of rebound like most people do.

37:14Before GLP-1s came on the scene, I was really concerned about the just overall metabolic health of our nation in general and how we were exporting it out to the world. And I mean, like I used to, I'm sure you have too, like it used to really keep me up at night. I was like, this is a disaster. We are a metabolic disaster as a society.

37:33Dr. Mark Hyman:That's why I've written like 20 books on the topic. I know, I know we are. And then I know, Right. And then COVID hit and I was like, oh, this is going to be a hot mess because it preferentially impacted folks with metabolic compromise the most. And I think that we're in a pickle and we have skyrocketing rates of infertility because of all of it. And nobody wants to talk about that. And we are not replacing ourselves at the appropriate rate to even survive. And there's entire countries that are going to be non-existent here in a short while because they're not replacing themselves. And so I don't know what it is.

38:08I don't know if it's toxicity. I don't know if it's the metabolic health. I don't know if it's all the things all jumbled together. But we needed an escape signal, right? And so for me, it's risk tolerance. It's like some of these folks are headed down a sure path. They're living a sub-existent, miserable life anyway. And they're headed down a sure path of demise or probably early death. and a lot of folks are getting their lives back. And so I have that conversation with people and I say, this is the risk tolerance, right? We're still going to do all the things. There's no getting out of that.

38:40You're still going to work your butt off. But I have a tool that might actually make this a lot easier and more efficient. The long-term risks, I leave that up to the patient. We don't know. We do know. I mean, we have had liraglutide and exenatide out for a long time and nobody's dying of cancer from those. And the data's looking really good.

38:58Dr. Mark Hyman:It might be dose-dependent, right? It might be dose-dependent. Why I like the way you think about things, Tina, is because you're talking about personalizing treatment, not one-size-fits-all dosing, not massive super physiological doses, just enough to do the job. And my guess is you're going to get less GI side effects, less gallbladder issues, less pancreatitis, less issues around diabetic retinopathy we're seeing, or even this new sudden vision loss, which is quite scary for people. All these things, the nutrient deficiency, if you're really conscious about how you do this and do a lower dose, you might be able to avoid a lot of these.

39:35Dr. Mark Hyman:Is that fair to say? Yes. And if you continue to work your butt off, you can stay on the lower dose. I find that to be true. I find that the minute people start slacking and they bring the alcohol back on board and they're eating out all the time, they're going to have to bring up the dose because the weight loss stalls if they're truly after weight loss. And so it's just like anything else. I'm always just having an agreement with a patient. We're in a journey together. I'm the cheerleader. I'm not just the drug dealer. Like we're really trying to overhaul their life completely. And I think that as long as they know going in that that's the deal, I will not.

40:11I mean, there's just no version where you should be allowed to take a GLP-1 and not be in the gym. Like you should have a prescription and you should hold to it. Just getting people to hold to it is the hard part.

40:21Dr. Mark Hyman:True. It's tough. And you really have to understand what you're getting into. This is not a, you don't embark on this and not be prepared. You know, you've really got to do it. It's really easy to dose yourself into anhedonia where you're just like, all of a sudden you lose all your luster for life. And then you just want to sit around. Patients on higher doses. The study came out showing they just don't move around as much because I think it's because of that. I think they kind of get into this malaise state and a little too much can be a lot too much. And so really working with somebody who's going to monitor you and encourage you to do all the things and help you get the resources to get there.

40:57Dr. Mark Hyman:Well, I think that's a really important point you make because most people are on the prescription versions. And what you're saying is, is it at those doses, we're seeing people's emotional range blunted, dulling their joy, causing apathy, what you call anhedonia, which was not having fun. I mean, is this related to the dosing issue? Is it related to just the compound itself? I think it's a dosing issue because the second you back them off just a little bit, all of a sudden they're actually I've seen people stall and I've heard other doctors talk about this. they stall out at higher doses and you actually bring their dose down and they start losing weight again.

41:32So there's a sweet spot. There's a really, there's a very particular individually sweet spot. I was just talking to my best friend who she started out microdosing. She really needed to bring the dose up to somewhere in the middle of the, you know, ladder and to really get the weight to come down. And she, that's fair. And she's really doing all the things, but she messaged me and she said, I took just the tiniest. I mean, she went from like 7.5 milligrams up to eight milligrams, just a little tiny bump. And suddenly she's flat as a pancake. Her affect's flat. She hates everything. She doesn't want to go anywhere.

42:04She doesn't want to do anything. And I was like, you dosed into soul crushing dosing. That's when it's crushing your soul. Back off a little. But then also, don't slack on the gym and make sure you're dialing, maybe decrease the wine a little bit. That's just how it is. And so it's not a get out of jail free card. you know, you still got to put all the pieces together.

42:28Dr. Mark Hyman:Are there things in the last few years that have emerged that we should know about it that are concerning? And is there any kind of new insights around that? Or is it still the same kind of list of things? No, let's talk about it. Because there's actually some really good data just dropped very recently. So the first one, I think we should talk about the NAION, the... No, I know the vision loss. Yeah. The eye stroke. It's non-arteritic anterior ischemic optic neuropathy. I have to read that off of my notes because I can never spit it out. But a study just came out July, 2026, JAMA ophthalmology, basically showing that it's an increase of about three hundredths of one percentage point.

43:06It's very, very low. And what they, what they really wanted to drive home in that study was that we're already talking about sick people living with diabetes for the most part is who they were analyzing. And so when you, and I did a podcast about this when the, scare first emerged, and you know this, but for your listeners, when you take somebody who's been living with diabetes for a really long time, their entire vascular system is messed up, really messed up. And when you remove, when you drop the glucose too fast using medication, if you go again, too fast, too hard, you know, maybe the dose is too high and too strong.

43:43The vasculature can spasm. It doesn't handle it well. You have to titrate them up. You can't just wampum with a dose. And so I do think that it's a signal. It's totally worth paying attention to. I'm not discounting it. But again, it's just more support for what I've been trying to say is we have to look at an individual's dosing plan and we have to get them what they need and do it in a careful stepwise manner while they're being monitored because we don't want that happening. We don't want to send somebody's blood sugar plummeting when we could just gently nudge their system back to a more normal state, healthy and normal.

44:18So we were talking about a JAMA study back in 2024. It was a 2023 study that came out and it looked pretty bad, but actually when you broke that one down, all it showed that when they looked at the numbers, they were giving you

44:33relative risk, not absolute. And so they were giving you relative risk reduction versus absolute. It's kind of how they played out with the intervention of 2021. You know, numbers get different and inflated. So anyway, that study, even when you broke that down, it was only two pancreatitis cases of semaglutide users. Of over 600 people, there were two pancreatitis cases, which we know pancreatitis is a real risk and you're seeing it. And then there was 71 pancreatitis cases in about 4 ,000 patients, which is also, I mean, worth paying attention to. But this new study came out in gastroenterology in 2025, and it was a better done study.

45:14And the finding was no significant increase in pancreatitis, bowel obstruction, or gallbladder inflammation. So interesting, not to say it's not happening at all, but it wasn't enough to be significant. And so I think just to piggyback on the end of that, if you are continuing to eat and crush down high fat foods and simultaneously you are dosed to a place where your appetite is so suppressed that you kind of stop eating or you slow your eating way down, your gastric motility is going to slow down when you stop putting food into the tube and your gallbladder is going to get sluggish. And these people probably already have sluggish gallbladder.

45:51They're already at risk for pancreatitis. Most of the people taking these medications are already having a lot of issues in the biliary gastric, you know, region, pancreatic region, it's already a stressed out system. And so now maybe instead of eating, you know, a big meal full of high fat fried foods, maybe they're eating a smaller amount, but still the body's not handling it well. They throw a stone, they get pancreatitis. So I just think it's, yes, again, it's a signal and it's worth noting and you're seeing it. I know people, I hear it from my followers that they have seen it too, or maybe a loved one's experienced it, just more reason to like do this right.

46:28There's a right way and a wrong way to do it.

46:30Dr. Mark Hyman:One of the things I talk about constantly with patients is the idea that the body isn't broken. It's just not getting what it means to do its job. That's really the whole promise of functional medicine. We're not playing whack-a-mole with symptoms. We're asking what do the underlying systems need to actually function. And one of the tools I keep coming back to in my own routine is my sunlight and sauna. Infrared therapy is one of the most underrated recovery inputs out there. and i say input intentionally the same way i talk about sleep or nutrition not a luxury it's a conditioning your body can use what separates sunlight specifically is your pulse iq technology until there's red light plus near mid and far infrared wavelengths independently so you're not just getting blended wavelengths plus heat you're getting a targeted personalized session now if you're already dialed in on food and exercise this is the piece most people are missing go to Sunlighten.com and use the code HiMini, you'll save up to$2 ,100 plus get free shipping.

47:24Dr. Mark Hyman:Have you ever climbed into bed exhausted, but your body just won't switch off? Your mind keeps racing, your muscles feel tight, and you can't fully relax. Well, a lot of times that can come down to one foundational nutrient, magnesium. It plays a critical role in sleep, recovery, stress regulation, and muscle function. Yet many people simply are not getting enough. And that's why I've recommended Magnesium Breakthrough from Bioptimizers for years. and now they've introduced magnesium breakthrough advanced 10 with 10 bioavailable forms of magnesium and even more elemental magnesium to support sleep muscle recovery and metabolic health it's become part of my evening routine especially during periods of travel training and higher stress go to bioptimizers.com forward slash hymen and use the code hymen to save 15 off your order let's let's move on from the side effects and the scary stuff because you know i think i've changed my opinion over the years on this.

48:12Dr. Mark Hyman:I, at first I was very against them and I was really skeptical and I, and I've changed my position because I, I've been following the research. I understand the complexity of dealing with people with metabolic health. Yes. If I got people to do it my way, I think we can get most of the benefits in terms of, you know, functional medicine, gut healing, you know, understanding food's medicine, how to, you know, give people a low glycemic diets that reset their metabolic system. I've done all this. I've seen, you know, cured autoimmune diseases and cured dementia and reverse diabetes, reverse heart failure and reverse fatty liver, and all these things are possible, but it requires quite a bit of work.

48:51Dr. Mark Hyman:And it's not everybody who can actually do this. And I think these are, I think, a real benefit to humanity. The question is, how do we use them right? So that said, I think I want to kind of dive into what's the difference between men and women taking these compounds? What's happening around post-menopausal women? What about fertility? There's a huge fertility crisis related to what used to be called PCOS, but it's other things as well, metabolic health. And now they're calling metabolic reproductive syndrome as opposed to polycystic ovarian syndrome. And I'm so happy about that because I've always said it's not an ovarian problem.

49:23Dr. Mark Hyman:It's a metabolic problem. And it's called, it's like it's people confused that it's a gynecologic issue, but it's not. So anyway, what's your perspective on this kind of hormonal effects and what's happening in these cases? Because I think this is a big issue. One in seven couples are infertile. It's a big problem. I think it's been miraculous because it's improving metabolic health. So men are experiencing improvement in testosterone levels. They're experiencing improvement in fertility. Women are experiencing improvement in fertility. There's whole Facebook groups that are dedicated to like Manjaro babies.

49:59People are getting pregnant on the GLP-1. That's still being, you know, we're still deciding if that's safe. I think I saw just a few weeks ago a position paper. Something came out. Don't quote me. I saw it in passing and I did not, I have not gone back and scrutinized it. But basically they're saying like we're not seeing adverse events of people who were on these got pregnant. Their offspring seems to be normal and healthy. So we don't know, of course, and we can't do studies on pregnant women, but people are getting pregnant and having babies when they were normally infertile and having issues.

50:33And so I think they're great. I think with PCOS or PMOS, the new term, I think it's great. I think it's, it works so great. I will say, though, I have seen with a couple of patients, young women with PMOS, if they're really androgen dominant, if they go in really androgen dominant and they're already dealing with some hair loss and they're already dealing with some issues around that, it's really critical that we onboard them slowly and carefully because I think that GLP-1s can put a mirror in front of anything you're already dealing with. So if you're already hypothyroid or you're already low in hormones or you're already imbalanced in your hormones and you start throwing GLP-1s at it, I think there can be a breaking in period that's very uncomfortable for people.

51:20And so ultimately, people do feel improvement in their thyroid health and they do feel improvement in their PMOS symptoms. I had a young gal. We had her on a microdose of semaglutide. Her hair started falling out like crazy. The androgen excess symptoms got way worse. it was a really, I mean, she could not tolerate it. She was not going to continue. And yeah, sure. There was work to be done and foundational work to be done, but it did not go well. And I've seen this a few times. So all that to say, and I get messages from people saying, I just couldn't tolerate it for whatever reason. All my hair started falling out.

51:54There's, so I think it, and there was one study, it was small. I can't remember if it was on rodents or humans, but it showed that GLP ones can maybe exacerbate that androgen excess picture a bit, maybe temporarily, we don't know. But I think that's worth noting for practitioners listening or patients out there, because some people are having a really hard time as they start and they're like, why isn't this working for me? I don't think they're for everyone. But I do think overall, yes, I think this might be a big helper in the whole problem because we do have a fertility problem. And then And with middle-aged women, I think it's just fantastic.

52:33I mean, it's just a, I'm living it right now. I am in the throes of the sudden belly fat, right? And they say, oh, middle-aged women are going into menopause, the menopause transition with their just low muscle mass. And that's the reason. And everybody wants to blame it on that. And their metabolism isn't slowing down. I went into perimenopause in the best shape I've ever been in my life. I was training for a strong first kettlebell competition. I had more muscle on me than like most women in my, like I was like in the 1 % of women my age. I was incredibly fit when I went into that. And I still got hit with the belly fat and the midsection and the visceral fat.

53:09And so I think what I just had a really great conversation with my friend, Kieran Krishnan, who's a microbiologist and a GI specialist. And he was telling me that what happens with a shift in hormones during the midlife transition has such a huge impact on our microbiome. And it also has a huge impact on our lipopolysaccharide levels. And when those elevate, they cause your fat cells to expand and to get bigger. So a lot of what's happening in this shift is coming from the gut first and foremost. And the really interesting part, just to like put a, you know, put a big blob of whipped cream on top of that is here's the crazy part.

53:50When you start stalling out the gut with higher and higher doses of GLP-1s, you exacerbate SIBO. I think a lot of people are coming in with SIBO, which is small intestinal bacterial overgrowth. I think they are getting SIBO along the way. I think it is, even microdosing exacerbated my SIBO when I had a really stressed bout of, huge bout of stress, like boom, my SIBO was like not happy. So that culmination, and I read one study, it was like a 45 % increase in SIBO with GLP-1 users. And I, again, I wonder if they came in with it, who knows, but here's the ironic part. SIBO pushes your LPS levels up.

54:27And LPS is what drives obesity and type 2 diabetes.

54:31Dr. Mark Hyman:That's lipopolysaccharides, which is a toxin from bacteria in your gut that gets absorbed and it creates inflammation. That inflammation creates insulin resistance, which then creates weight gain, diabetes, and the rest of the cascade. So that mechanism is pretty well described. So yeah, that's interesting. So the medication they're using to treat the obesity and the type 2 diabetes is in fact driving potentially the obesity and type 2 diabetes. So this is where I think an integrative approach is non-negotiable. Like you have to treat the gut. I've gotten so many people better for metabolic issues by treating their gut.

55:00Dr. Mark Hyman:It's quite effective. 100%. So Tina, let's talk about what people should think about before they want to start GLP-1s and what kind of blood tests or metabolic markers should people look at before prescribing. One of the first things I noticed with GLP-1s is that your labs will start to shift sometimes even before the weight loss starts coming down or even if we're not going for any weight loss whatsoever and we're on a small dose or tiny dose, we'll get great improvements. So I want to see those. So I want to see fasting serum insulin. I want to see hemoglobin A1C. I want to see C reactive protein, inflammatory markers.

55:32Obviously we run a complete blood count and a complete metabolic panel. So we're looking at liver and kidney function from the start to make sure nothing's shifting there or going in the wrong direction. We might throw in some nutrients in there. I am concerned about malnutrition with these. I think people get themselves malnourished. And a study just came out showing, it's all over the internet right now, like brain damage from GLP-1s. It's not brain damage. These people are sitting on the edge of a thiamine, a B1 deficiency, which is super common. And then they get thrust into malnourishment with the high doses.

56:07And then they go into Wernicke's encephalitis and they end up with terrible, Frank, B1 deficiency issues.

56:13Dr. Mark Hyman:So people should check their nutritional markers and vitamins and minerals and get replete, like take a multivitamin along with it. And look at your lipids, of course, and look at your thyroid markers and just make sure everything's staying cool. I think with middle-aged women, it's important to look at, and men, it's important to look at your hormones. I just, I run such a comprehensive panel on everyone. I hear you. I hear you. I mean, honestly, I agree with all you're saying. And I think that, you know, most people should check all those things anyway. And I think it's part of why I co-founded Functional Health, which is if you'll access in a very affordable way to a very deep panel of blood work, which includes all those things you mentioned, including nutrition, hormones, thyroid, cardiovascular markers, metabolic markers, renal markers, fatty liver, all of it.

56:59Dr. Mark Hyman:And at Functional Health, it's just basically a dollar a day to get this done twice a year. And I think it's important for people to track things while they're doing it, see the changes, monitor things. Super important. All right, let's talk about the kind of newer therapies and next generation therapies. And also, let's dive a little bit into the sort of microdosing framework, because it seems like the drug companies themselves are understanding that their doses are too high typically, and that they want to give the possibility of adjusting doses by different sort of offerings they're having, like vials or different pens that have a titration ability on the pen.

57:35Dr. Mark Hyman:So can you talk about what's happening, what's coming, and how do we think about the dosing both? Because there's this whole gray market of people just buying them online or from, you know, Mills or telehealth, and it's not actually probably safe. So can you kind of walk through how do people navigate this? We're listening to don't want to take the full dose or trying to figure out how to look for the right approach. So the dose really depends on the person and their genetics and all the things we just mentioned and what their goals are. What are their short-term goals? What are their long-term goals?

58:06I will say this, microdosing, the way that I originally introduced it was just a fifth to a tenth of the standard starting dose. And I would dose up to the, you know, the bodybuilders know this, right? The bodybuilders are the original biohackers. They understand this concept. It's the minimal effective dose to move the needle of whatever needle we're trying to move. So maybe someone doesn't want to lose any weight, but we want to get their inflammation under control, or we want to get their joint pain, or their psoriasis, or their psoriatic arthritis, whatever, their eczema, their acne. It's the minimal effective dose.

58:38And so that is, I have found totally different for everyone. It men, you asked me about men versus women, men, I find need a higher dose. They, women are more sensitive to it generally, but maybe that's just based on body weight. Maybe that's just size overall. And their hormonal status matters. We've got one study, it was small, but we've got one study looking at trisepitide and GLP ones, and they did better when they were on HRT. They had more appreciable weight loss. There was a smaller study done a couple of years ago. I think we mentioned it on the last one. It was such a tiny study, but again, people who were on GLP-1s did better with weight loss when they were on HRT.

59:13So I think the whole milieu of the patient really matters there. And I want to be very clear. I never intended microdosing to be a weight loss strategy, but that's all it's being marketed for. And these companies are preying upon middle-aged women, telling them they're getting a microdose and they're actually getting a standard dose. They're just being started at the first tier of the same dose that the folks with diabetes and the same folks with obesity get started on. And they're told it's a micro. And it's an onboarding strategy. It's like drug dealers who give you your first dose free or whatever just to like.

59:48So that's kind of scammy. I've even had, I've got people arguing with me in my comments saying, no, I'm on a microdose. And I'm like, no, honey, you're like on the third tier up of the standard ladder. Like you're not, you're not on a mic. But my doctor said, what they tell him is, yeah, we follow Dr. Tina's protocol. It is one 10th of the dose. And they tell him what the max dose is. And because they're giving them one 10th of that, then it must be a micro dose. So that's super unethical and scammy to me, but that's everywhere. And that's what a lot of these companies are seeing, especially the telemedicine ones are doing that I found.

1:00:20So that's frustrating. And then I just want to, there was a study that came out in May of 2026. I don't know if you saw it, but they looked at, they did a study. They looked at 49 different online telemedicine GLP-1 websites. And this is scary.

1:00:31Dr. Mark Hyman:49 is scary in and of itself. Yeah. We started a whole craze with that last episode. 17 sold compounded only, five sold branded only, and 27 sold both. Two required blood work. One denied a prescription based on internal data indicating an existing prescription from another website had already been filled. And one prescribed but later withdrew the prescription due to a mismatch between the patient's photo and reported weight. But basically, 39 % asked about weight loss goals. I'm sorry, 39 of the 49 asked about weight loss goals. And on and on it went. They did not screen these people very well.

1:01:11And only 13 required a video visit and three required to call. So basically you can go on, fill out a form and get GLP ones sent to you is the end of the, and they're not doing a comprehensive workup on you. Not all telemedicine companies are like this. Some are really good, but yeah, this is pretty scary. And then the other option is the gray market, like you mentioned. And I mean, I don't, that's just, that's, I think that's just gotten completely crazy and I don't know what to say about it anymore. I don't have an opinion because too many analysis are coming out showing there's nothing in the bottle or there's contaminants or there's LPS.

1:01:47Dr. Mark Hyman:Exactly, which is concerning. Yeah, but the cool thing is, is the brands, Eli Lilly and Novo Nordis, released their vials. I don't know if you know this, the week that Eli Lilly released their Zetbound vial, I got deplatformed off Instagram at 232 ,000 because apparently they didn't want me talking about what I was talking about. Really? Yeah, but I don't know. It's just coincidence maybe. anyway they release their vials and I think these vials allow for more individualized dosing and from what I know from my colleagues that's what they're using they're using it to microdose they're using it to standard dose they're using it to half so now if you go to a your doctor they can actually prescribe these drugs from the pharmaceutical company in a vial that allows you to self-administer with a syringe at a lower dose so it's not an auto pen is that the idea Yep.

1:02:37So it's personalized, individualized dosing so people can onboard. That paper came out in the Journal of Diabetes in 2025, I think, or end of 24, talking about microdosing GLP-1s. But the way that they talked about it was, it was published. It was an opinion paper. It wasn't a study. But the way they talked about it was individualized onboarding. So they're talking about microdosing differently than I am, and they're talking about using it to get your patient up to the appropriate dose, but you can start them lower if they need it because people definitely need it. A group out of Italy was reporting that they're finding a lot of success with individualized dosing.

1:03:14I think doctors are getting it. I think doctors are realizing we're all different sizes and shapes. We all need a different individualized strategy. But I do know that Monjaro, I believe, came out recently in the U.S. with not just the standard auto pen, but the clicky pen. You can dial the end. And this Journal of Diabetes paper did give you a whole chart. And I know that's available in Europe, a whole chart on how to change your dose or your patient's dose based on how many clicks you do. So it's called the click pen method. And so we've got a lot more options than we did last time we talked.

1:03:47And the price has come way down.

1:03:49Dr. Mark Hyman:So the good news is you can get them from legitimate pharmaceutical manufacturers. You can get them at lower prices. Probably the truth is the prices are higher with these pharmaceutical versions than the ones that are available through other markets, right? I think it depends, actually. The compounding situation with GLP-1s is so hairy right now that I've seen prices kind of all over the board. And some of these companies really gouging, some of these telemedicine companies really gouging patients. so I don't think so I think the I think Medicare just got you can do a Medicare program now$50 if you go through Lily direct and get the Zetbound in the vials the pricing is is quite depends on your dose I don't know and I I'll say though the clients I've got a few clients I work with who are getting prescriptions from their doctors and the Zetbound seems to be working better than the compounded for them for weight loss.

1:04:46Or the other thing to consider when weight loss stalls is you just change your injection site. And so a lot of people will get comfortable kind of sticking to the same place all the time. Maybe it's the outer buttocks or the thighs or the belly or the arms. And so something that was my friend actually just mentioned it to me. She's like, oh, I just started rotating my sites and the weight fell right off. And I was able to back off that dose that was sucking her soul out. So she, yeah, so there's just a lot, a lot of variation here. I think we're learning and it's fun to be able to talk with you and have a fun conversation about it.

1:05:20That's educational. So people can get all the information.

1:05:24Dr. Mark Hyman:Yeah, it's good. I mean, it's evolving and I think people should, should really work with a reputable practitioner who understands how to use these in conjunction with lifestyle, doing the right diagnostic tests beforehand, understand what's going on with your metabolic, nutritional health, hormonal health, and kind of monitor things like DEXA scans and your bone density and your body, you know, muscle mass and really tracking things. Cause I think without that, it's, it's, it's, it's, it's a very slippery slope. Um, I want to, I want to end by sort of doing some rapid fire questions. Are you up for that?

1:05:55Yeah, I'm ready.

1:05:57Dr. Mark Hyman:Okay. So you mentioned like alcohol and how it might interrupt, uh, the cravings or addiction in general, but what's the deal with alcohol and GMP wants? Can people drink? Can they not? How does it work? I would get off the alcohol. I really would. When you slow down gastric emptying, the alcohol stays in your stomach longer. So what you're used to consuming and thinking you can handle changes. So if you think you could handle one or two drinks and get in your car and drive, you can't anymore. It's also a poison. It's poisoning your mitochondria and your mitochondria being poisoned are part of the reason why you can't lose weight.

1:06:29So it's kind of an oxymoron. If you're going for weight loss, it's really you're shooting yourself in the foot with alcohol on that one.

1:06:34Dr. Mark Hyman:Find other drugs. All right. Got it. What about the mistakes people make on GLP ones? I think what we talked about, just using it as the plan, you know, like using it as the solo monotherapy plan. Like that's, I'm going on Ozempic or whatever, and that's it. It's like, no, no, no, no, no. It's that is a, but one tool in a comprehensive toolbox and you really have to do all the things. And what's the biggest misconception people have about this medication? That they're eating your muscle and bones. It's not true. Well, you will lose muscle and bone if you don't exercise, but that's because any weight loss will do that, right?

1:07:09Dr. Mark Hyman:Yes, yes. Okay. What's the thing everybody should know before starting? What you just said, that you should work with a reputable clinician who knows what they're doing, who understands integrative functional medicine, does a comprehensive treatment plan. I think that's key. And I know not everyone can access that, but at the very least, go to the freaking gym and start eating nutritionally dense foods. Start there. And who shouldn't take these GLP-1 drugs? I'm really concerned. I live in north of Scottsdale now and I'm seeing all these weight loss clinics and they're treating little old ladies who have no weight, who really have no right losing any weight.

1:07:43As we age, that little bit of extra weight might actually be protective. And these women are worried that they're fat. And so they're taking GLP ones. And I just had one of my friends, his grandma fell down and fainted and almost broke her hip and was in the hospital because she, they're already headed towards frailty if they're not going to the gym regularly and they're not protecting their muscle. And then they've got GLP-1s on top of it. I think it's crazy and super unethical.

1:08:08Dr. Mark Hyman:So be careful in older people who aren't really obese. That's what you're saying. And young women who are not really obese, who are using it for vanity, weight loss. Not a vanity drug. I mean, people are getting into trouble. I agree. What's one lab test you wish doctors paid more attention to related to all this? Serum insulin. Hey, I knew you were going to say that. oh man i used to catch hell from my colleagues and they're like why are you testing everyone's serum insulin you think everybody's metabolically compromised i'm like they are and here we are no it's terrible i mean i i went i was uh been testing insulin for 30 years and i just talked to the the lab guys at quest who is our function health partner and i said what percentage of tests that you get are including insulin an order seems like less than one percent i said no yeah And I was talking to the dean of the medical school in Arkansas, Bentonville, the Alice Fountain School of Medicine, who's of East Indian descent.

1:09:06Dr. Mark Hyman:And she's a doctor, and she's actually a fan of mine. She was listening to my podcast. And she's a gynecological oncologist as her specialty, but she's the dean of medical school. And she went to see her cardiologist and said, will you please order insulin for me? He's like, no, you don't need it. And she's, yeah, but I'm Indian. and I find out this is a problem for me. It was quite amazing how it's one of those tests that is so simple, so cheap, so easy to do and tells you so much that nobody's doing. And if you take one thing away from this podcast, you've got to get your insulin down under 10, ideally under five.

1:09:40Dr. Mark Hyman:And that's what a lot of this stuff will help you do. Okay, what's the most surprising thing you've seen happen to a patient that had nothing to do with weight loss with these compounds? Oh gosh, just the addiction piece. I think, like I mentioned, the eating disorder, I'll tell you one. me, I was taking a microdose of trisepatide. I was wearing a CGM. My blood sugar is dangerously low all the time, like so low that it sets off the device and the alarm goes off. When I use GLP-1s, it puts my blood sugar back in the normal range. And I've heard and I've asked many people and they have seen similar.

1:10:17So yes.

1:10:18Dr. Mark Hyman:It's like a paradoxical effect almost. Yes. And then the addiction part and the eating disorder part. I think those are things we didn't expect. Okay. That's good. Those are important things. What's something people don't worry about with these drugs that they should worry about? Their muscle, particularly their lower body. If you're going to lift, if you're going to take a GLP when you have to lift, and if you are going to go spend time in the gym, you really have to, especially you ladies, as we're aging, we are protecting our bones and our muscle. And you have to lift lower body because it's your biggest metabolic sink, that biggest bang for the buck.

1:10:51Everyone's so obsessed with these Demi more arms. And I'm like, can we just build a dump truck? Like we need to build an ass. Like at the end of the day, that is what's going to protect you from a hip fracture. You have to go to failure and you have to progressively overload. So find someone that can help you learn with that. I talk about it all the time on my social media, my podcast, but that's critical.

1:11:10Dr. Mark Hyman:Agreed. Agreed. Agreed. I was doing that this morning. My butt hurts. Good. So what's one thing the internet has completely wrong about you if you want? That they're made from snake venom and they're going to you know, that literally directly derived. There's a doctor out there, a chiropractor saying, and I'm a chiropractor too, so no shade, but every single prescription is derived from, it has venom in it. Okay. How about one thing that you would change about how these meds are prescribed today? What would it be? Oh, I think it's just the wild west. And I think people have, I hate to say it. I am such a libertarian and I believe people should have access to medications without too many hurdles.

1:11:49But I think it's just too crazy right now with the gray market and even the telemedicine companies. And then really just my concept of microdosing being bastardized and twisted into some vanity weight loss thing that was never intended. And it's kind of where we're at. So I think it's, that's a way off base.

1:12:05Dr. Mark Hyman:But, but also you do say that the microdosing does help with weight loss too, though. And that just says, well, a half dose, I mean, a half dose could, if someone is really metabolically optimized, it can lead to, you know, 10, 15 pounds of sort of that inflammatory puff or that middle-aged kind of like that menopausal insulin resistance weight that comes on. I think it can help with that. But I think if you're looking at the average middle-aged woman who's looking for weight loss with a microdose, she's probably looking at more of a standard dose or a half dose or three quarters of a standard dose.

1:12:39We're not, I'm not talking to like micro microdose. Like I have little old ladies on tiny little doses for their joint pain. Totally different beast.

1:12:48Dr. Mark Hyman:What's the biggest unknown we're trying to answer? Well, like you said, what is coming in 20 years? And I am concerned. I think we're going to see there's like quad and, you know, there's like the five different agonists, the four, they're coming out with all kinds of fancier ones. And I'm seeing a lot of people who have gotten to the top tier of dosing. They're still living with obesity. Maybe they're not doing all the things. Maybe they are. I'm not judging, but they're looking for the next medication to come out because they've peaked and now they're gaining weight back. And so I think we're going to see this with a lot of people to your concern and mine just kind of running to the next one.

1:13:23And it's just a long line life of kind of being tapped into a drug. It's a scary thought, honestly.

1:13:33Dr. Mark Hyman:I hear you. It is. It is a wild west. And it's like, there's a quote I always talk about, which is from the New England Journal of Medicine that said, we should use new drugs as soon as they come out before the side effects develop. We don't have to know. Okay. So on the positive side, what's the most exciting GLP-1 area research now? Cancer. I think it's really exciting to see. There's two studies that came out recently showing potential prevention with, and it's not causative, it's correlative from what we have. It's observational, but breast cancer. But to your point, when you optimize metabolic health, then I mean, I remember being what was it the year I got my medical license?

1:14:16It was like 2008 and I was downtown Portland and the Susan G. Komen walk for the cure was happening. And it was all of these little cute ladies in pink T-shirts with fairly girthy midsections carrying boxes of voodoo donuts and drinking giant Starbucks Frappuccinos. And I was looking at my, it was a bunch of naturopaths up in a room at a conference and we're looking out the window and I'm like, this is, this is not it. This is not it. This is why we have breast cancer. It's metabolic health. So I'm excited to see that benefit play out. But at the end of the day, we got to treat the root cause.

1:14:55Dr. Mark Hyman:Amazing. Well, Tina, thank you for keeping your eye on the ball, for helping us under a very complicated field of weight loss, metabolic health, GLP-1s. I think it's really such an important advanced medicine, but also it's fraught with a bit of risk. And I think doing it right is really important. And hopefully those who are listening, if you're able to do it right, where can they find more about your work, Tina, and learn more about how you think about all this? Yeah. Well, thank you again so much for having me back. I appreciate it. It was nice to be able to just talk with you one-on-one and get the information out doctor to doctor.

1:15:26So I have a community I'm launching. I'm so excited about it. You can actually access me in there and I can give answers. It's for middle-aged women. It's called the menopause rebellion. And so that's at school, S-K-O-O-L.com forward slash Dr. Tina. I have a podcast, the Dr. Tina show and everywhere you can find me. It's D-R-T-Y-N-A and that's my website too, drtina.com.

1:15:48Dr. Mark Hyman:Great. Thank you. Thank you so much for just keeping on this and helping us all understand this very messy, complicated field. Thank you so much for having me. It was fun. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in.

1:16:19Dr. Mark Hyman:We'll see you next time on The Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services.

1:16:48Dr. Mark Hyman:If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible.

1:17:18Dr. Mark Hyman:Thanks so much again for listening.