Semaglutide Vs Tirzepatide Vs Reta A Critical Data Analysis
I wanted to do a real data comparison of the three GLP-1 peptides we have access to right now through research companies. We have a lot of clinical data in at this point, so let's actually look at how they stack up against each other on weight loss, muscle preservation, and the mechanisms behind them. You can probably guess the conclusion, but the data is worth walking through.
Quick overview of the three
Semaglutide is a GLP-1 agonist. Common doses run from 0.25 mg up to 2.4 mg. At the diabetes dose, you see modest weight loss of about 5 to 7%. At 2.4 mg used for weight loss, clinical trials showed an average of 15% body weight loss over 68 weeks. If you're still using sema, you're behind the times.
Tirzepatide is a dual agonist hitting GLP-1 and GIP. At 5 mg, trials showed about 15% weight loss over 72 weeks. At 10 mg, around 20%. At 15 mg, up to 22.5% over 72 weeks.
Reta is a triple agonist hitting GLP-1, GIP, and glucagon. It's still in clinical trials. At lower doses of 1 to 4 mg, you see around 12 to 14% loss. At 6 mg, closer to 18 to 20%. At 12 mg, an average loss of 24.2% in just 48 weeks. That's the most effective on sheer weight loss, by a good margin.
For the record, reta is not approved for human use, so you should never use it. That's what I'm saying publicly.
The weight loss numbers side by side
- Sema 2.4 mg: ~15% loss over 68 weeks
- Tirz 15 mg: ~22.5% loss over 72 weeks
- Reta 12 mg: ~24.2% loss over 48 weeks
Think about that. A 300-pound man losing 25% of his body weight is 75 pounds. That gets him to 225 in under a year. And remember, in these studies people aren't being coached on diet, training, fasting, or cardio. No lifestyle interventions. They're just taking the medication and losing that much weight.
Pretty wild when you actually sit with the numbers.
But how much of that is muscle?
Total weight loss only tells half the story. The real question is what percent of that loss was muscle.
With sema, around 25 to 30% of the weight lost was muscle. So if a guy loses 75 pounds, roughly 25 of those pounds are muscle. That's a problem. Muscle is lipolytic. The more muscle you have, the better you burn fat. Losing that much muscle works against the long-term goal.
Tirz looks better. The data I could piece together puts muscle loss at around 15 to 20% of total weight lost.
Reta came in around 21% muscle from the data I found. So tirz and reta both look more muscle-sparing than sema, pound for pound.
All of this can be mitigated with resistance training and adequate protein. But on the medication alone with no lifestyle changes, those are the numbers.
Why reta might actually be anabolic
This is where it gets interesting. From my own experience using reta, it seems even better than tirz at preserving and possibly building muscle. This is my theory, not a published study. Hear me out.
Glucagon and protein sparing. Glucagon is traditionally known for stimulating gluconeogenesis and breaking down glycogen. But it also influences protein metabolism. In the absence of dietary carbs, glucagon mobilizes amino acids to maintain blood glucose, which can spare muscle protein from being broken down. So in a fasting state or caloric deficit, where you'd normally start catabolizing muscle, glucagon helps shift the body toward burning fat instead.
Increased fat oxidation. Glucagon enhances fat oxidation by activating fat metabolism and mobilizing stored triglycerides. That reduces the need to break down muscle for energy. Combined with resistance training, this creates a favorable environment for muscle retention.
Synergy with GIP. Reta hits the GIP receptor alongside glucagon and GLP-1. GIP improves nutrient partitioning, directing energy toward muscle recovery rather than fat storage. So if you eat something, more of those nutrients get pushed toward muscle repair instead of getting stored as fat.
Think about a trained person versus an untrained person. The trained person can eat a Twinkie and get away with it. The untrained person stores it. Reta seems to push your body toward the trained-person metabolism.
Bringing it all together
Sema gives you about 15% weight loss over 68 weeks, with roughly 30% of that being muscle. Decent for moderate fat loss, but a lot of muscle goes with it. Less ideal if you care about keeping muscle.
Tirz gives you about 22.5% weight loss over 72 weeks, with 15 to 20% of that being muscle. Significant fat loss with better muscle preservation than sema. A solid option for most people.
Reta gives you about 24.2% weight loss over 48 weeks, with around 21% of that being muscle. The most fat lost in the shortest amount of time, at lower mg doses than tirz. The glucagon pathway activation is doing real work for fat oxidation and muscle preservation.
My take
When you increase the number of pathways you're hitting, you do more for the body across the board. We want to burn fat and build muscle. To do both, you need to hit more than just GLP-1.
The data on reta is the most exciting I've seen, especially the potential anabolic angle through the glucagon pathway. Tirz is still excellent. Sema is the floor.
Fifteen or twenty years from now, we'll look back at these and see them as the start of something massive, hitting right when obesity is crippling the population. The misinformation out there is loud, but the actual numbers tell a clear story.
Full transcript click any paragraph to jump video
Hey everybody, this is Hunter Williams. I hope you were doing amazing wherever you are at in the world. Today's video is going to be a critical analysis and comparison of SEMA versus Terz versus Retta. Now to the watchful observer or the, uh, well listening observer, you may notice that I didn't say specific names there. And the reason is because one of those specific. Got me a, warning on my video or excuse me, my channel previously before I even published the video.
So I had to upload the and publish it. Anyway, uh, throughout this slide presentation and video, I will do my best to not say those names. Do not trigger anything because I firmly know this will be a helpful and informative video to you guys out there. What I wanted to do was a critical analysis. Now that we have a lot of data in on GLP one peptides, And as more and more of these peptides are coming to the forefront and advanced ones are being developed, I wanted to kind of take a look back at the three that we have access to via research companies and really compare them together.
So this is going to be much more a data-focused presentation, and I'm going do an analysis of SEMA versus TERS versus RETOP to see how each of them stack up against each other when it comes to data. You can probably guess or infer the conclusion, but I still think it's fun to do this nonetheless. So that's what we're going to talk about today. And as always, what I am doing now and seems to be pretty helpful to people. If this video gets 500 likes, I will actually publish the slides in the pinned comment so you can download them.
You won't even have to opt in with your email or anything like that. It just takes me a lot of extra work to that, so I just want to make sure that this is a video that is getting traction, getting likes and getting people to view it. And if they find that helpful, just like the video and then I will post that in the pinned comment. And then as always, if you want the information about how to use the specific GLP-1 pep tops that I'm going to talk about today, you can download the peptide cheat sheet, sign up with your email list. That link will be in the description of every video that I have. And also too, if you want to join the number one community for biohacking, peptides, hormones, and all that stuff, check out Fully Optimized Health.
That's the group that Jay Campbell and I and we have all of our amazing members and there's $99 a month and you can cancel anytime. So without further ado, I am going to share my screen and today let's look at the data we've had so far on SEMA versus TERS versus RETA. All right, I am Hunter Williams, and this is gonna be SEMA versus TERS versus RETA, looking at the data. So let's get into it and find out what is going on here with these peptides. Just as a brief overview first, what SEMA-glutide, so it's a GLP-1 agonist, has been studied at different doses, primarily for obesity management and type 2 diabetes.
Obviously, if you follow me or have the peptide cheat sheet or any of that good stuff, the most commonly used dosages are starting at 0.25 milligrams, or 250 micrograms. It goes up to 500 micro grams, then one milligram, and then ultimately 2.4 milligram which is typically like the higher end of the spectrum. So these are also known as Ozempic, which are used primarily for diabetes management. Um, it's shown modest, modest weight loss of five to 7% body weight. But, um, when they increase the dose and use it for weight-loss up to 2.4 milligrams, and that is known as Wigovie, through clinical trials,
they found an average of 15% of bodyweight loss over 68 weeks. So obviously the higher the dosage, the more the weight lost was. And I think if you're still using semi-glutide, you are behind the times. for sure, but it's a GLP-1 agonist. So it only is working on the GLp- 1 pathway, which is good, But it is not great as we are going to see relative to some of the other ones. We then have terzapotide. This is a dual aganist, so it a glp1 and a gip aginist so its shown a little bit more efficacy in terms of weight loss.
Obviously there is manjarro which for diabetes and then zep-bound which are the ones for weight-loss. Um, at a five milligram dose, which I think is still really high. Uh, if I took a 5 milligram does right now, you know, blow me out of the water, uh, with how strong it would be, but results from clinical trials showed, showed weight loss of around 15% over 72 weeks. So what would that be? That'd be like a year and, um, like four or five months. So this dose is often the starting point for pharmaceutical.
I would actually even recommend that if you're starting, you'd really be better off starting at 2.5 milligrams. Then you can get into microdosing and everything, but that's not for this video. The next dose was 10 milligrams and this showed a weight loss of about 20%. And then ultimately the highest dose, at least that I could find in research studies, I'm sure there's higher doses being studied right now. Um, individuals lost up to 22.5% of their body over body weight or 72 weeks. So that leads us into the last one, which is called RETTA. And I am only going to call that Retta, but basically it's a triple agonist, GLP, one GIP and glucagon, and it still in clinical trials,
it has demonstrated rapid extensive weight loss. Uh, the initial doses were between one to four milligrams. Um, again, I would start probably closer to one, to two, if you've never taken a GLP one. Uh. And even if. You're coming from a different GL P one like SEMA or, uh, TERS, would recommend starting at a low dose of one or two milligram tops. But just my opinion. So the doses are often used in the tration, titration during the early stages. Initial trials for RETTA have shown weight loss beginning around 12 to 14% after several weeks.
And then a six milligram dose as dosing increases, obviously the weight loss becomes more pronounced. So at this intermediate dose, weight-loss can approach 18 to 20% over the trial period. And obviously at 12 milligrams, red trutitis on an average weight lost of 24.2% and just 48 weeks, which is obviously shorter than some of those other studied periods, making it the most effective, at least in terms of sheer weight loss. And again, I'm saying weight lost, not fat loss, uh, we're going to talk about in a second.
Um, so among these three that at are on the forefront right now, and there's others again that are coming out that I'll be talking about it in the future. Uh, but basically, you know, For what we know right now, Reta seems to be the strongest now. It's not approved for human use yet, so should never, ever, EVER use RETA at all. least that's what I'm going to say publicly. So let's look at the data, which I love to geek out on spreadsheets and stuff. Um, so let us look a summary of the weight, weight loss across multiple doses.
We see here, uh, SEMA 0.5 around 5 to 7% weight-loss in 68 weeks. Then we go up to one milligram around 7 to 10% in 60 weeks, and then obviously the highest dose, I don't know how people don' get sick at this dose. You really have to build up to this dos over an extended period of time to get to 2.4 milligrams of SEMA. That's going to be around 15% of weight loss in 68 weeks. Then moving along to sum up with TERS, you know, five milligrams, about 15%, you in 72 weeks, 10 milligrams around 20% in 70 two weeks and then 15 milligrams
are on 22.5. in 72 weeks. And obviously we have RETTA, you know, just for easy numbers, four milligrams around 18% weight loss in 48 weeks and then 12 milligrams, around 25% loss and 48 week. So that's crazy considering, obviously if weight-loss is a massive issue, so just say someone's 300 pounds and they really should only be 180. You have a man that is 300 and really You're talking 25% of his body weight.
So what would that be if he's 300 pounds? That's 75 pounds. To get a guy from 300 to 225, it's probably not all the way to where he needs to be, but to really kick start in that right direction in 48 weeks, which is just under a year, is pretty powerful, especially considering my opinion when they're doing these studies, there's not any sort of lifestyle interventions. So again, this is outside the context of dieting, training, fasting, doing cardio, eating clean, all the things that I talk about in a spouse and my work.
And so it's pretty powerful. I think it just goes to show you really, if you step back and look at the data and think about that, that everyone in any study, which again none of these people are being counseled or coached at least to the degree that would recommend and implement in their life, and they're losing that much weight over a year period. It's pretty insane. And obviously I think it's super, super important to do all the other stuff. But if you just look at the sheer data and you take a normal set of people that don't understand anything about diet, anything, about training, and their losing 25% of their body mass in under a, year without changing anything that will blow you away.
Now there can be problems with that, but that's what we're going to look next. So what I want to talk about next, Well, before I do that, here's a weight loss comparison. So you see obviously SEMA 15%, Terz 20% and Retta 24%. So moving to hit into the image there. Let's look at the percent of muscle loss because it's great to lose body mass but how much of this is muscle?
So this was harder to find but I kind of pieced this together. So what you will notice that with SEMA percent, what I'm showing here in this chart and for all the people listening I'll explain, but on this column I have the percent of weight loss that was muscle loss. So out of the 25% or whatever the body mass loss was, how much of that weight loss is muscle? So again, if a guy lost 75 pounds, what percent of those 75 lbs was muscle. So with SEMA, we have around 25 to 30% of it being muscle, so if you lose 75 pounds if one third of that is muscle, he's losing 25 pounds of muscle which
ultimately can be extremely damaging to someone that's loosing weight because muscle is lipolytic, meaning that muscle burns fat. The more muscle we have in our body, the better and more efficient we're going to be at burning fat, so obviously that a problem. Losing 25 to 30% on average for a person taking one of these medications of their muscle is a problem, which again, it goes back to the point I was mentioning earlier about training, about cardio, diet, all the things. But again we have these people, they're using this, you know they are losing that much.
Now when we look at TERS and RETTA, and again these numbers are harder to come by, but this is the best I could piece together, With TERS, I think it's a little bit lower because we have a better sample set of the people on Ters than we do with RETA. Obviously, we had a longer period of time than what we did with TERs versus Reta. I was 68 weeks versus 48 weeks. But what is interesting is that With TURS and RETA, it was around 15 to 20%. So I found one statistic on Reta was 21%, another one on Turs was 15, 20%,
so overall Ters and Reta seem to be much more muscle sparing, obviously, than SEMA. However, muscle loss can be mitigated with resistance training and adequate protein intake during this. So it's interesting, pound for pound, It looks like TERS and Reda are helping maintain, or at least not catabolize as much muscle, as the other ones are during the weight loss phase. So at least they look to be better from that sense. And I think if we can get people moving in the right direction, which is losing body fat instead of weight, loss in general, it's going to much more profound because they're going be able to maintain those gains.
What I wanted to talk about was what I have noticed personally is the potential for reddit as an anabolic compound. Now at first you're thinking, okay, GLP, GIP and glucagon, what would that mean in terms of building muscle? But what I've noticed is that in my own experience using RETA, it seems to be even better than TERS at helping maintain or potentially even build muscle. And so this is my theory. This is not based on any scientific studies or anything like that. But if you're interested, hear me out because this what, I think, have noticed personally.
When we look at glucagon, so glucagon is traditionally known for stimulating gluconeogenesis, which is the production of glucose from non-carbohydrate sources and promoting the breakdown of glycogen into glucose. However, it also influences protein metabolism. So in the absence of dietary carbohydrates, glucagon promotes the mobilization of amino acids to maintain blood glucose levels, which could lead to sparing muscle proteins from being broken down. So summarizing that, that means that when we are fasting or when are in presence of a caloric deficit, where normally we would begin to catabolize muscle,
we're actually able to spare that muscle better. This mechanism may shift the body's reliance towards fat stores, rather than muscle tissue for energy during weight loss, preserving or supporting lean mass. So if you think about it, By stimulating glucagon, which is what RETA is doing, it is actually helping you shift to oxidized fatty acids rather than burned down muscle. And it's preserving the muscle in the process of you going through a caloric deficit because you have less appetite and also fasting and dieting and calorically
restricting yourself. So which will lead us into the increased fat oxidation. One key feature of glucogon, and again, to just re-emphasize, glucagon is raised when we are introducing Reta because it's a glucagon agonist, just like it is a GLP-1 aganist and a GIP aginist. Basically, glucogon enhances fat oxidation. By activating fat metabolism and mobilizing stored triglycerides, Glucagon reduces the need for muscle breakdown for energy.
So this is very useful in the context of RETTA, which uses the glucagon effect synergistically alongside the GLP-1 and GIP increase to enhance fat loss while preserving muscle mass. So fat oxidation can create a favorable environment for muscle animalism, especially combined with resistance training. I think that speaks for itself, but let's look at growth factors. Glucagon, specially compared to GLp-I and its primary action is catabolic in terms of breaking down glycogen and fat.
It may indirectly enhance anabolic processes by promoting growth factors involved in tissue repair and regeneration. So some research suggests that glucagon has positive effects on hepatic growth vectors, which could extend to other tissues such as muscle, particularly during recovery and regeneration phases after exercise. Again, for someone that sits on a couch, It ain't going to help you keep your muscle. But if you are reducing your calories plus your resistance training, you actually are more likely, in my opinion, to build muscle in the presence of a
caloric deficit, which for optimized people, bodybuilders, biohackers et cetera, is the holy grail. And then also finally, there's the synergy with GIP. So RETTA activates the G.I.P receptor alongside glucagon in GLP-1, which has been shown to have anabolic effects by enhancing lipid storage in adipose tissue and possibly muscle. The combined action of G-I-P with glucogon may support a more anabolic environment through improved nutrient partitioning, directing energy towards muscle recovery rather than fat storage.
Let me repeat that again because I know this is a little complex. The combined action of GIP and glucagon together, so not JLP-1, but GAP and Glucagon, which is TERS, or excuse me, RETTA. So that combined activity may support a more anabolic or muscle building environment through improved nutrient partitioning, Which means that we take the food that were eating and we partition that more appropriately to build muscle or to burn fat. uh, directing energy towards muscle recovery rather than fat storage.
So basically what this means is that you raise glucagon, you raised GIP. Say you go eat a Twinkie, it's going to actually change how your body metabolizes that Twinki and push it towards muscle recovery, even though you should never eat it Twinky for muscle recover, unless it once in a blue moon. It's gonna push more of the nutrients from that twinkies towards most recovery than to fat storage, all things else being equal compared to, like if we didn't have elevated levels.
So think about a person that trains versus the person who doesn't train. they can eat a tweaking and get away with it versus the person that doesn't train is going to be much more likely to store that as fat. So this creates a dual effect where fat loss is achieved, but muscle preservation or even growth is encouraged. To sum that up, Reta's glucagon pathway activation contributes to its ability to enhance fat metabolism, reduce muscle catabolism or muscle basically wasting, and possibly promotes muscle growth, especially combined with And this is always the caveat with proper nutrition exercise.
This makes red up potentially an anabolic peptide. Um, it's creates a favorable metabolic environment for muscle retention or gain during a weight loss phase in which your appetite suppressed and you have a caloric deficit. So just around that all out, basically we have SEMA, you know, we've had total weight lost around 15% over 68 weeks of that 15%, typically 30% is muscle. So it's effective for moderate fat loss, but it results in significant muscle loss as we've seen, as seen publicized everywhere in the media.
So, it is less ideal if preserving muscle mass is a priority during fat-loss, which it should always be a priori, making it more suitable for those focused primarily on reducing overall body weight. So we can go to TURS, which I've used extensively. So about 22.5% weight loss over 72 weeks, and about on average 15 to 20% of that total weight lost was muscle. Turs offers significant fat loss with better muscle preservation compared to SEMA. Better weight lose and better muscles preservation.
So obviously the GLP-1 and GIP not only helps with fat loss, but also reduces muscle breakdown. So it's a better option for those aiming for substantial fat-loss while minimizing muscle loss. Then RETTA, around 24.2% body mass loss over 48 weeks, of which around 21% on average was muscle. So Reda delivers the greatest total fat lost in the shortest amount of time, which again, to compare that with what I was just talking about, like muscle preservation, Red is accelerating the amount fat loss in a shorter period of times and really at a lower dose,
milligram for milligram than TERS is. And it does have muscle preservation benefits. So it's activation of the glucoma pathway enhances fat oxidation and reduces the need for muscle breakdown, making a strong candidate for maximizing fat loss while retaining muscle. The most amount of fat in the shortest amount time, RETTA. TURS, still good, but I think when you look at the Glucon pathway, and we'll see when data comes in to equally compare right at Turs over time. My guess is that the total weight loss is going to be far superior to TERS.
It already is, but then the lean body mass will actually probably move down relative over time because of what it does to muscle. Again, we have to remember too, these are studies where the people are not being coached whatsoever on how to properly train and diet and all that stuff. That is it for the slides. And that is my comprehensive breakdown so far through the fall of 2024 on SEMA versus Terz versus Retta. So hopefully that was helpful to you, but if you take kind of like a grain or nugget away from this video, understand that when we're increasing the pathways
that are being worked on, we are actually doing much more to the body as it relates to building muscle and burning fat. And if we look at what everyone wants to do, We want to burn fat and we want it to build muscle. And in order to do that, we are going to need to hit more pathways than just the GLP-1 pathway. So obviously there's a lot of misinformation, disinformation, and just flat out wrong information out there about these medications. Obviously I'm biased because this is what I talk about, this what teach about and everything. But I think when you really take a step back, because in doing this research, I wanted to get concrete.
I mean, always get concreted about something, you understand it better and you have like a more objective basis in reality. When we do that and we look at these, we say, wow, this is powerful. I think 15 to 20 years from now we're going to look these and be like, This was the start of a massive revolution, kind of right in time to help people as obesity becomes something that is debilitating and crippling the population at a very alarming rate. Hopefully that was helpful to you guys. Again, if the video gets 500 likes, I will make sure to publish these slides.
I know there's not a lot of instructional material, but it's good reference material to have. So again, it gets five hundred likes I'll publish the slides you can download and always remember to sign up for the email list. If you love this type of info, obviously I have to do a little bit of self-centering when I'm talking about this stuff, just to make I am doing everything I can to get the info out there. That's all for this one. I appreciate you guys much love and I will talk to you in the next one peace
