Survodutide & Mazdutide | The GLP-1/Glucagon Duo That Could Rival Reta

(upbeat music) Hey everybody, this is Hunter Williams. I hope you're doing amazing wherever you might be in the world. Today's video is going to be all about two peptides. They're not super new, but I think they're going to become very popular in the near future as an alternative to reddit. And these peptides are servodutide and mass-dutide. Now what these peptides are, is if you could imagine redda, which is a GLP plus a GIP plus a glucagon agonist, we actually, when we remove the GIP component of redda, which is what makes transeptides, transeptides, when we remove that, we get just GLP and just glucagon agonism. And there's two peptides actually right now. They're going to talk about today that only work on these two pathways and they seem to be maybe a little bit superior than the other two pathway agonists, which would be transeptides. So we're going to go into that today. I think these are going to become more popular. The end of the day are they going to be as good on paper as reddit. No, obviously not. They're only a two stage agonist instead of a three stage agonist. However, I think there could be useful in a couple of situations. One, we have a situation where someone is on reddit true tide, maybe for too long of a time, and they want to cycle off of it, but they're scared to go off of it. We could insert these new two peptides, which I know are still hitting the same pathways, but because they are a different peptide, they're going to work a little bit differently and we're going to get a little bit better receptor sensitivity in that case. And so you don't have to fear. You can stay on a GLP but actually rotate through them to get a little bit better receptor sensitivity. And then also too, I think this is going to be pretty cool is for some people that don't do well on reddit true tide, particularly because of the GIP agonism, which might make them sick or it might make them nauseous. I think we're going to be able to use these two peptides. And servo dutide, mass dutide differ a little bit in terms of what proportion of the peptide handles GLP versus handles glucagon. And so we'll go into that. But I think for someone that wants to get some of the benefits of glucagon agonism, which is going to include mainly burning liver fat, but also the increase in metabolism. In the increase, I think when we look at base metabolic rate, we're going to see a big increase with glucagon agonism relative to just the GLP and the GIP. And so I do think there's a use case for these at the end of the day, at least on paper as it stands right now. Reddit true tide seems to be superior. However, when we look at these, I think there's going to be a use case for them. And I think they're going to become a lot more popular, maybe depending on the regulatory environment and how that goes. I think there was a big scare about people not being able to get redd a few months ago, but it seems like that is really subsided. And so that's where we are going to cover today. As always, thank you guys so much. I have so much gratitude for the overwhelming amount of support I get from you guys. So thank you so much. If you're watching this on my Spotify channel, I do have a new podcast channel on YouTube. So we're going to maybe get my personal channel back. But all the long form podcasts that I interview guests, I'm going to be posting on that. So just Google search Hunter Williams or YouTube search Hunter Williams podcast. It'll come up and go follow there. But just make sure you're on the email list as censorship seems to be on the rise. That's the best way to stay in touch with me. Make sure you can get updated with all the new videos and new content that I put out. So thank you guys so much. And obviously to check out the action on collective, that's my private coaching group. You never there. We do live coaching calls every Thursday night at 8 p.m. Eastern. You can also directly message me to ask me questions. At this point, I'm getting so many questions from so many people, which is amazing blessing in my life. But I have to prioritize who I respond to and how I respond. And I prioritize those people first, because they're my primary group. So check that out without further ado, today we're going to talk about servo due tide and mass due tide. All right, let's get into it. Today we're going to look at mass due tide and servo due tide. You may have seen these out in the wild out there. Maybe being sold on some websites or being talked about. So let's go into what they do today and then how we could actually practically use them. So, uh, JLP one August have obviously changed everything. We have single agonist, ozempical govy, similar to the double agonist, terzo appetite, monjaro, zep bound, and then red, a true tide. I don't know what the name of red, true tide is going to be yet at the time that I'm filming this video. But we've got these other two ones, mass due tide and servo due tide. And they don't just suppress appetite, but they actively increase energy expenditure and torch liver fat. And I think when we look at a double agonism peptide, you would actually probably say for the long term health benefits, this might even be a little bit better than terzo appetite. Now, we're going to look at some numbers today on paper. It might not be as good for fat loss. But I think when we look at red, a true tide, what's a power about it? Powerful about it is this glucagon agonism and we're going to be getting that through these. So, um, we're going to look at those. And then obviously too, I think in terms of liver fat, we're going to see a lot more benefits there. So, let's look at the two compounds who they are, where they're from, what they do. Mass due tide is a synthetic analog of oxen to mojulin developed by in-event biologics and dented drumroll. Eli Lilly. It was approved in China in June of 2025 as Zen Air May. I don't know how to speak Mandarin, but someone could probably correct me. In the world's first approved glucagon and GLP1 receptor agonist and US trials are in phase two and they're ongoing. FDA approval was estimated not until 2028 to 2029. Now whether or not that's just because they want to have this profit window on transeptive red true type who knows. But that's what we're looking at at least in the news stories that I could find. Then we have servo due time, which is a 29 amino acid peptide co-invented by Bowring Dr. Ingleheim and Zeeland pharma and is not yet approved anywhere, but it holds FDA breakthrough therapy since October 2024. EMA prime since November 2023 and China NMP a breakthrough since June 2024. Designations for mass wishes metabolic associated steatosis. Something. So, I forget what mass stands off the top of my head. But it basically is non-alcoholic fatty liver diseases. Now I guess to that until let's let's look at what these do and why adding glucagon, which you already probably know, but let's look at why adding glucagon changes everything. One we have the GLP one side, obviously that's the all the rage, right? GLP one suppresses appetite, it delays gastrochromatine, it stimulates insulin secretion, it inhibits glucagon from alpha cells. This is very familiar, we're all familiar with this hundreds of millions of people have used GLP one peptides to this point. But when we look at glucagon specifically, and again, this might be remedial for some of you guys out there that listen to me or follow the peptide world, but when we look at glucagon, we really get this energy expenditure component. A cute glucagon infusion raises caloric expenditure by around 200 calories per day via hepatic fuel cycling, FGF 21 thermogenesis. You remember the sugar diet craze, everyone was talking about this hormone FGF 21, which burned fat. When you go on a fruit fast, you raise levels of FGF 21, which then burned fat. And then brown fat out of post site activation directly counteracting metabolic adaptation. And basically what glucagon agonism does is it increases the calories that we're burning at rest and then has this cascade of fat burning, which is why it works so well. We also look at liver fat, glucagon activation increases hepatic beta oxidation. It suppresses denovolipogenesis and restores mitochondrial function. And then the these are effects that GLP one agonism alone cannot replicate. And that's why we look at fat loss just beyond the GLP one agonism. What's so important? And it's also important to know there is no hyper glycemial list risk. GLP one component counterbalances, glucagon glucose raising tendency and mass due tide showed superior HBA one C reduction versus Cima gluteide. Basically, if you look at injectable glucagon itself, which is not glucagon agonism, like we're talking about today, in the diabetic world, injectable glucagon would actually be used to inject who raised someone's blood sugar. So if they have a blood sugar crash and the blood sugar is too low, maybe they took too much insulin, you could actually administer glucagon and this would help raise their blood sugar. Now, you'll probably ask yourself, why would I want something that's going to raise my blood sugar? And the reason is is because it's increasing this energy expenditure. However, when we pair it with the GLP one, it's going to counterbalance the glucose raising tendency of glucagon agonism. I don't think at least from what I've seen that the glucagon agonism itself is directly raising blood sugar as much as identical or bioidentical glucagon would that a diabetic would inject in the situation that just mentioned. However, when we pair it with the GLP one, it's going to modulate that and actually because we're reducing visceral fat and getting an increase in metabolism, you're actually going to see a reduction in A1C, which is one of those lagging indicators of how metabolically healthy someone is. Now, I can say myself, my fasting insulin, my blood sugar, my A1C, all those things have never been better since I've used redotruthide in the last two years that we've had access to redotruthide. But I think it's important to understand that about a glucagon agonism. And I also too get asked, hey, is there going to be just a glucagon agonist peptide? There may be, I would be interested to see, and I'm not saying one way or the other, but I would be interested to see if a peptide that was solely a glucagon agonist would have the effect of actually raising blood sugar while burning fat because we know that it's going to do that. But does the GLP necessary to actually help modulate and stabilize blood sugar while we're agonizing the glucagon receptor? Potentially. I don't know, but it's just a question I had when I was preparing this because it is mechanistically something that we look at. Let's look at some benefits just beyond the scale. And this is going to relate a lot to liver fat. MazduTide is six milligrams a week in patients with baseline hepatic stiotosis. They saw 80% liver fat reduction, which is crazy. We also saw 62% resolution of mesh in servo duTide at 4.8 milligrams per week. And then peak weight loss, MazduTide at nine milligrams in non-diabetics in one trial in 60 weeks led to 21% weight loss. And again, that's why I say it's not as strong as you would see with red true tide, but still pretty dog on powerful. And I think if we look at that and having another peptide that is getting pretty close to acting the way that red true tide is, but we can use that as maybe even just something that we're cycling in between our red true tide. I think that could be really cool. MazduTide produced A1C reductions over around 1.5 to 2.15%, which is kind of crazy as in comparison with monotherapy of just the GLP component alone with superiority of redo-glute tide and semi-glute tide and phase three trials. And then we will look at cardio metabolic markers, both peptides reduce waist circumference, systolic blood pressure. I get asked all the time about, hey, is there a peptide for blood pressure? Yeah, there are some peptides for blood pressure, but again, I think people overlook the GLP's at how powerful those would be for blood pressure, improvements in triglycerides, improvement in LDL, improvement in uric acid, and servo duTide's liver enzyme drops were dramatic. The ALT and the AST, Sodiumatic Drox, and Boeringer has launched the first GLP one in Glucogon. cardio vascular outcomes trial with around 5,000 participants. And that is ongoing right now. Now, let's look at some MazduTide trial by trial data and the glory one trial, I don't know where they come up with the names of these trials, but hey, glory sounds cool. And all the glory of using your MazduTide, 49.5% of six milligram per week participants lost more than 15% body fat liver fat dropped around 80% versus 5.3% in placebo. I always read these studies and aggregate the data and think, man, how much would have sucked up in the placebo effect, thinking you were going to, or thinking we're potentially we're going to get something that helped you lose weight and it didn't, but maybe it helped them change their lifestyle a little bit because it did actually help bring it out 5%, it just wasn't 80%. Glory to trial, the 9 milligram dose saw around a 20% weight reduction and that was again in the non-diabetic's. 48.7% of the people saw greater than a 20% threshold burning in their body weight and the curves did not plateau at week 60. So it seemed to continue after that. And the dream three trial, another trial, world's first phase three had to head versus seem a gluteye to with MazduTide 48% versus 21% weight loss. And that was greater than so, excuse me, the weight loss was 10% versus around 6% with seem a gluteye, sorry, I was misreading that data point. And then the high dose phase in the US population 20 weeks around 20 to 21% weight loss, around 66 to 75% achieving greater than 15% reduction in body weight and they clearly had not plateaued. When we look at servo dutide phase two obesity trial had 3,387 adults over 46 weeks. At 4.8 milligrams per week, they saw around 18.7% weight loss, around 40% of those people achieved greater than 20% weight loss. Phase two, a mash trial, 293 biopsy confirmed patients at 4.8 milligrams per week. There's a 62% mash resolution meaning they completely healed their mash or fatty liver versus 14% on placebo. 67% achieved greater than 30% liver fat reduction. 36% improved fibrosis and this earned at stage or FDA breakthrough therapy designation. Phase two and type two diabetes people, this was in 2024, 411 adults on that form and 1.8 milligrams of servo dutide weekly. There a one C went down by 1.71%. The highest twice weekly dose around an 8.7% weight loss versus 5.3% weight loss for seem a gluteye at 16 weeks. And then finally, the phase three program which is ongoing. And the results are expected in quarter one of 2026 at some point and we don't have those yet, but it does have a seven year follow up of them. So we should get some pretty good data. We look at dosing and I want to talk a little bit about this because the dosing is similar, but it's also a little different. Mash do tie we have once weekly subcutaneous injection. The approved doses in China are 4 milligrams and 6 milligrams per week. The hydration is two milligrams to start then to four milligrams and then to six milligrams with around four weeks is typically the prescribing guideline for there. And then the nine milligrams is the highest dose. Excuse me and China that's the highest dose. The US is evaluating three six 10 milligrams and 16 milligrams doses and around 50% of the participants on 10 or 16 milligrams achieve greater than 20% weight loss at 48 weeks. I think if we look at right true tide, I want to say it's 24% weight loss at 48 weeks. And so it's really creeping up to be as good although on paper, not as good yet. With server due tide, we have once weekly subcutaneous doses well, base three target doses are 3.6 milligrams and six milligrams. Now guys, I don't know how we get 3.6 milligrams instead of three or two instead of three. If you've used GLPs, you know that sometimes an increase in the dose can make a difference. But then also two, it's like, why would I do 3.6 milligrams instead of three? I don't know where that comes from. Maybe it's a molecular weight thing that the chemists do and it's just easier for them to make that. But anyway, those are the starting and then in face to trials, aggressive biweekly escalation, drove high discontinuation. I think I put that data point in there because I know I put it in there because I think when we look at this, escalating the dose of a GLP two-fast leads to problems. And this is where we have to be very careful without we do this because I think people went gung-ho whether it was doctors or just people in the research world where we were first started doing this. They went gung-ho just escalating the doses really nilly and then that leads to really bad side effects. So please just as a reminder, I put that in there to make sure you're being conscious and cognizant of how you're escalating the dose. Face to three trials, redesigned with slower four-week individuals dose flexibility and option to pause and restart if GI side effects become intolerable. Now let's look at the tolerability gap and this is going to go into what proportion of these are more GLP or more glucagon. And so we'll look at this. Masuteid had a remarkably clean tolerability. So discontinuation due to adverse events was only 0.5% at six milligrams. Think of this for a second. The placebo discontinuation was 1%. Now did that 1% discontinue? Probably because they were mad because nothing was happening. But only 0.5% at the 6 milligram dose discontinued. Even at 9 milligrams, only 2.9% of those people discontinued. Compare that to wigovie or zepound seem to be considered a tarzapatide. Typically, we're going to range somewhere from the four to seven percent. And so the most common GI events with Masuteid or diarrhea decreased appetite. Obviously nausea, vomiting. There was no pancreatitis, no thyroid carcinoma or severe hypoglycemia reported. And pretty interesting. The heart rate increase was around 2.6 beats per minute at week 48. Now the reason I say that's interesting. This is going to lead to something in a second is because when we look at right at true tide, what I typically see is with right at true tide relative to the dose someone is doing their heart rate is going up five to 10 beats per minute, usually within a few weeks. Here we see week 48 2.6 beats per minute, which I think is pretty cool. And that's going to lead to something that we talk about in a second on the composition of these contrast that with server due tide. There is more of a GI burden. And this going to be conservative due tide has a higher proportion of GLP one agonism than it does glucagon. And so when we looked at the phase two to trial, around 66% of people got nausea. 49% got diarrhea. I mean, that sounds like seem a glutei to me. 41% got vomiting and discontinuation was around 20 to 24% mostly during rapid by week of the escalation. Again, don't recommend that. And the phase three uses slower titration to address this and serious adverse events were actually lower with server due tide when they started titrating them over four weeks at a time and set up two weeks at a time. The adverse events were actually lower with server due tide than placebo. Again, another case for please, if you're going to escalate the dose, do it in an intelligent manner. I can't stress that enough, but there was no glucagon driven hyper glycemia observed, which was pretty interesting. Now let's look at the receptor map here. We look at GIP versus glucagon, the different target. So GIP, which is what's her zapotide enhances insulin secretion. It improves sensitivity, insulin sensitivity, and buffers GLP one induced nausea. It is not increased energy expenditure or directly act on the liver. And that's what I'm saying. Like if I could have server due tide or mass due tide versus trizzapide, I don't know. Maybe I'm going to go with mass due tide or server due tide. I'm going to personally be experimenting with this myself and see where it goes. But we look at glucagon agonism, mass due tide and server due tide, they increase energy expenditure by around 200 calories per day. They directly stimulate hepatic fatty acid oxidation and they restore mitochondrial function, which we're not really getting out of the GIP agonism. Maybe a little bit, but not so much. And then again, this is not something that we're going to get out of trizzapide. Whereas right at true tide, obviously combines all three. We have 24% weight loss and pay for trials and 82 to 87. a percent liver fat reduction. It's about two to six percent more liver fat reduction than Mazu Tide or server two tied, but still pretty good. That's why I'd say red and true tied is still the king. However, it's pretty cool that we have these other ones on the block. Now, I think this is important to note when we have GLP versus glucagon, this is where Mazu Tide and server two tied are different. When you see these out there sold in the research where you think, oh, they're the same thing. They're a GLP and a GLP and a glucagon agonist. Same thing, right? Not entirely. If you think back to what I just said a second ago about the tolerability of Mazu Tide versus the tolerability of server two tied, here's why. Server two tied, we have it being GLP one dominant, meaning then about, and this is the best approximation I can make. Don't take this as the gospel. I took some studies and I did the Dalton weights and everything and I used some formulas and used some AI to come up with some formulas. So again, don't take this as Bible, but it appears that the ratio of GLP want to glucagon agonism in server two tied is eight to one, meaning that for every one part agonism of glucagon, we're getting eight parts GLP. Now that sounds like seem a gluteye light to me almost like it seem a gluteye with a little bit of glucagon agonism. And so we get stronger appetite to pression with that little glucagon cherry on top. However, with Mazu Tide, it's almost not exactly, but almost 50 50, meaning we're getting 50 percent GLP agonism with 50 percent glucagon agonism and slightly in favor of glucagon agonism. And of course, with that, we get more direct hepatic fat oxidation, which explains why it's so good at reducing liver fat. And so when we have Mazu Tide, 50 50 GLP one to glucagon, server two tied eight to one GLP to glucagon. And so the GLP one effects, we're going to get stronger appetite suppression of the blood sugar. Whereas the glucagon effects, we're going to get increased calorie burn and better torching a liver fat. And that leads me to the question, which one is better? Well, it really depends on your situation. Do you need to burn more liver fat and do you need to have more of a metabolic modulator that's increasing energy expenditure or do you really, really struggle with appetite suppression and you just want a little bit extra energy burning on the side over seem a gluteye. That would be the difference. And I can't answer that question for you. I know for me, I don't, I wouldn't say like my appetite's completely out of control. So I would probably lean towards Mazu Tide because I would want more of that energy expenditure rising. And that would be okay, probably the lower dose, because I would get good appetite suppression out of it. So when we look at these just across drugs, so when we have seem a gluteye, 2.4 milligrams per week with the max weight loss was 16%. We have Mazu Tide, 6 milligrams per week, max weight loss was 14%, a little bit lower. Servo dutide at 4.8 milligrams, the max weight loss was 18.7%. Mazu Tide at 9 milligrams, max weight loss was 20%. Mazu Tide at 16 milligrams per week, max weight loss was 21%. And then transapotide at 15 milligrams per week, the max weight loss was 22%. And so we'll see here these, if you look at Mazu Tide and transapotide together, that's pretty much equivalent at where they're at in terms of the fat loss there. And so it's transapotide for the dose, which is almost identical to the Mazu Tide dose. We're getting about the same amount of fat loss, which is pretty interesting because we have two, a two pathway agonist working on different things, but we're actually like getting pretty close. But on paper, transapotide would seem to be a little bit better, at least in that case, dose for dose. And then reddit true tide max weight loss, 24%. Obviously, that would still be king. These were, I would have to go back and look at the timelines, I believe these were all around 48 weeks or so. Maybe give or take. I do think this, this Mazu Tide one was around 20 weeks. But just to give you an idea of how they're working. And so just some takeaways. This is kind of a new paradigm in the GOP world. It's been out for a little bit, but I just don't think people have realized it as much. Mazu Tide seems to be superior and then servo dutide seems to be pretty good at reducing liver fat as well. And so when we look at decision framework, transapotide is going to be the best weight loss plus tolerability. If we want GLP one and glucagon, we can get Mazu dutide or servo dutide to add energy expenditure to superior and superior liver benefits. And then with retro tide, we're going to get the best of everything. So red true tide still seems to be king, but we will see where it goes. And for all you, all you guys out there, those are the sources so you can screenshot that and look it up if you want to or you can join the private group to which I will have links to the slides for all my videos. And you can always do that. And as it slides. And that is my intro to servo dutide and Mazu Tide. There's one thing you're probably wondering about what I didn't really cover in the presentation, which is what is the starting dose. And I didn't really want to do that because I wanted to kind of present this first and just germinate the idea. I think for someone starting out, it's obviously a question of where are you coming from. Because if you're coming from 12 milligrams of red up per week, the dose for use probably going to look different or you might need to scale down your dose of red up and then introduce servo dutide or Mazu Tide. If you're just starting out, I think it's perfectly reasonable to start to one to two milligrams per week, see how you do and then kind of work your way up from there. These again are going to be different than turns out to try to retro tie. If you have experience with those, so I would say always start low and you can always go a little bit higher. But it does seem to be one of those things that when we get into like that eight to 12 milligram range, the benefits really start kicking in. Now does that mean everyone needs to go there? Absolutely not. For me, five milligrams per week of red up is really when I've pushed myself about all I can tolerate without feeling disgusting and sick. But that's not going to be someone else. Someone might need to go to 12 milligrams of red up per week to really get where they want to go. So at the end of the day, it's up to you. But I would just say starting out the smart thing is always start low, even if it's just one to two milligrams per week and then kind of escalate as needed. And again, as we saw in that day to today, people are much more compliant and much better able to stay on the peptide for longer. If they escalate the dose every four weeks and every two instead of every two weeks. But just keep that in mind when you are scaling the dose that seems to be, I think the minimum amount of time that you would need to be on the peptide at a certain dose before you start to escalate it up. So hopefully this was informative and helpful to guys. And I think something to really get excited about is we head into these next two years. From a regulatory standpoint, my guess is probably as good as yours. I don't know where we're going to go. If they're going to crack down on these or whatnot, but it does look like at least right now, they're pretty easy to access in the research world as is right at true tide. And you can kind of test them out and see where they go. But I think at the very least, it's a good alternative to have to maybe get some more receptor sensitivity back to right at true tide, but also keep the gain strain going. So to speak and make sure that you are keeping momentum headed in the right direction. That's it for this one. Thank you guys so much at the end of every episode, even if it gets annoying. I just want you to know how grateful I am to be able to bring these messages to you. It's like a dream come true for me to get to do this and whatever shape or form that you support me, whether it's just watching these liking, commenting, subscribing, sharing it with your friends and family, using my code with affiliate sponsors. And also people that are in my private group and being on the email list. Thank you guys so much. It means the world to me that I get to do this. Hopefully that comes across in the material that I present to you guys. But thank you so much because without you, I don't exist. I look forward to your feedback. Have it an awesome day wherever you're out. And I will talk to you in the next one.