Is Retatrutide the King of Fat Loss? Latest News & Study Breakdown
Eli Lilly just dropped some interesting data on retatrutide, and this time they actually looked at body composition with DEXA scans. We have plenty of data on total weight loss with these GLP peptides, but until now, we didn't know much about how much of that weight was fat versus muscle. So let's get into what the numbers actually show.
The study setup
This was a phase two, double-blind, parallel group, placebo-controlled, randomized trial. Gold standard markers across the board. Conducted at 42 medical centers in the US, with a 3-week screening, 36-week treatment, and 4-week safety follow-up.
Participants were 18 to 75 years old with type 2 diabetes, A1c between 7 and 10.5%, BMI of 25 to 50. They had to have stable body weight for three months before enrolling.
The arms included placebo, dulaglutide (an older GLP-1), and retatrutide at 0.5 mg, 4 mg, 8 mg, and 12 mg doses. Some of the higher dose groups titrated up over time.
Out of 534 screened, 281 enrolled, 189 sub-study participants got DEXA scans, and 103 completed treatment with scans at week 36.
Total fat mass reduction
Here's where it gets interesting. Percent reduction in total fat mass at week 36:
- Reta 0.5 mg: 4.9% reduction (not statistically significant)
- Reta 4 mg: 15.2% reduction
- Reta 8 mg: 26.1% reduction
- Reta 12 mg: 23.2% reduction
Wait. The 12 mg group lost less fat than the 8 mg group. That's a notable finding.
Does that mean 8 mg is the sweet spot? Maybe. The 8 mg group titrated up over time, so perhaps that scaling matters. Sample sizes were small (18 in the 8 mg group, 14 in the 12 mg). But it's worth paying attention to.
Even at 0.5 mg, you saw nearly 5% fat reduction. So microdosing might have a real place if you're already lean and just want an edge.
Total body weight loss
Looking at total body mass change at 36 weeks:
- Reta 0.5 mg: 2.6 kg
- Reta 4 mg: 9.50 kg
- Reta 8 mg: 16.8 kg
- Reta 12 mg: 17.55 kg
- Dulaglutide: 0.8 kg
- Placebo: 2.01 kg
Placebo actually outperformed dulaglutide. So dulaglutide is basically worthless for fat loss. Reta at 4 mg and higher beat both placebo and dulaglutide easily.
Lean mass loss
Absolute lean mass change at week 36:
- Reta 0.5 mg: 0.4 kg lost
- Reta 4 mg: 3.1 kg lost
- Reta 8 mg: 6.5 kg lost
- Reta 12 mg: 6.4 kg lost
- Dulaglutide: 0.4 kg gain
- Placebo: 0.6 kg lost
Again, 8 mg and 12 mg lost essentially the same amount of muscle. So more dose doesn't mean more results. The 8 mg looks like the sweet spot here.
Visceral fat reduction
This was probably my favorite data point. Visceral fat is like kerosene to your body, and it does the most damage when it sits at high levels.
- Reta 0.5 mg: 3.6% reduction
- Reta 4 mg: 19.1% reduction
- Reta 8 mg: 29.4% reduction
- Reta 12 mg: 31.4% reduction
Even the 4 mg dose dropped visceral fat by nearly 20%. And remember, most of these people aren't changing their diet or hitting the gym. Imagine the results with actual lifestyle work behind it.
The 8 mg group also showed a 9.1% reduction in trunk-to-leg ratio versus placebo, plus a 3.6% reduction in android-to-gynoid ratio. Both are strong cardiovascular risk indicators.
The fat loss index
This metric tells you the quality of the weight loss. It's fat mass lost divided by total weight lost, expressed as a percentage. We want to see 60 to 80% of weight loss coming from fat, with only 20 to 40% from lean mass.
Across the 4, 8, and 12 mg groups, the mean fat loss index was 64.6%. So roughly 65% fat, 35% muscle.
Compared to other treatments:
- Semaglutide 2.4 mg: about 60%
- Semaglutide 1 mg: about 60%
- Tirzepatide (5, 10, 15 mg): 74%
- Bariatric surgery: 74%
- Retatrutide: 64.6%
Tirzepatide actually had a higher proportion of fat lost than retatrutide in this comparison. Small sample sizes, so take it with a grain of salt. But it's worth noting that we shouldn't dismiss tirzepatide just because reta drives more total weight loss.
The key takeaway here. Reta's fat-to-muscle loss ratio is similar to other therapies, but the total weight loss is greater. So you're losing more weight overall without sacrificing a worse muscle ratio.
Safety profile
No deaths. Eight participants had serious adverse events. Most common side effects:
- Nausea: 17%
- Diarrhea: 13%
- Decreased appetite: 11%
- Constipation: 9%
- COVID-19: 7%
- Vomiting: 6%
Fatigue ran 10% at 4 mg, 12% at 8 mg, and 3% at 12 mg. If you're using reta and dealing with these, you're right in line with the data.
My take
Retatrutide is still the king, at least for now.
The big takeaway for me is that 8 mg looks like a sweet spot. The 12 mg dose didn't beat 8 mg on fat loss and lost the same amount of muscle. More is not always better.
Reta drives more total weight loss than anything else we've seen, and the muscle-to-fat ratio holds up against other therapies. That's the answer to the lingering question of whether reta was just causing more muscle loss alongside the bigger numbers. It isn't.
By the time reta gets FDA approved, I think we'll have something even better in the pipeline, especially when you factor in muscle preservation and growth alongside fat loss. The next 12 to 18 months are going to be interesting.
Full transcript click any paragraph to jump video
Hey everybody, this is Hunter Williams. I hope you're doing amazing wherever you are out in the world. Today, I'm doing something a little bit different. Actually just did another video like this on SLU, but today I am doing a study review video on red true tide. So we obviously have a lot of data around red of true tides coming out. It's not FDA approved yet, But it will be pretty soon, probably in next year or two, depending on how fast they move it. But there was a recent study that came out with red a true tied funded by none other than Eli Lilly, the people that love us so much, They actually did look at body composition.
So they did some DEXA scans in the study and they actually measured the amount of total weight loss versus the number of fat loss and even visceral fat. I thought that was pretty cool and something that would definitely be video worthy as RetroTide continues to demonstrate that it is the king as far as peptides go, at least for now until we come up with something better. some of the data came back from those DEXA scans and look at how red trutide stacked up to some the other different GLP peptide.
So, spoiler alert, it was better. Well, in terms of, the amount of muscle loss, It was about the same, but there was greater total weight loss from red true type. So retrotide so far has shown the most total weight loss when it's stacked up against any other therapy, but it did not cause any more muscle loss than any therapy did. So pretty interesting, and that's what we'll go into and look into some of the numbers today. As always, check out the peptide cheat sheet down in the description of this video.
I'll also make sure to include a link to the study. in this video, which I think you can see the summary of. You probably have to pay for the whole study because I know I paid for this study to look through and compile all the slides and everything. But that'll be down there. And then as always, check out Fully Optimized Health for The Best Private Community on the Planet to talk about topics such as these. So without further ado, I'm gonna turn my screen and today we're gonna find out some more data about All right, I'm Hunter Williams, and today we're gonna be looking at this study, which was called the effects of Reta-Trutide on body composition in type 2 diabetes.
So this was a phase two, double-blind, parallel group, placebo-controlled, randomized trial by Eli Lilly and company evaluating how RETA-TRUTIDE affects body competition in people with type two diabetes, so let's look at the background of this. Obviously, obesity is a significant health concern linked to worse outcomes in many disease states, including type-2 diabetes Weight reduction is key in diabetes management as it improves cardiovascular risk factors. You know what's interesting about type 2 diabetes is almost always it is reversible.
So as new treatments for obesity and type-2 diabetes with greater weight reduction become available ensuring quality weight-reduction without excess lean mass loss is critical because our muscle is our metabolic currency. It doesn't behoove us to lose all the weight in the world if we lose over muscle in a process because then we're gonna have any metabolism and we are not gonna be able to live strong and live functionally and live an awesome life. Serrata Truetide is a novel synthetic molecule, in case you haven't heard of it, showing potent agonist action at three receptors which are the glucose-dependent
insulinotropic polypeptide, otherwise known as GIP, the glucagon-like peptide one, AKA GLP-1, and the Glucagon receptors. This is why it's called the triple G. So previous studies showed HbA1c decreases up to 2.2% and body weight reduction up 16.9% at 36 weeks, which is pretty cool. Limited evidence existed on changes in body composition. We have all this information on total weight loss. but relatively little information on body composition related to all these different peptide therapies for weight loss.
So, they're from smaller participant populations using a bunch of different means. I'm sure calipers, bod pod, dexa, you name it. At least in this case, we have a standardized measurement. This study reports changes in body compositions related multiple doses of ratatrutide in people with type 2 diabetes, and unlike approved agents for treating obesity, ratratrutite acts as an agonist at glucagon receptors, And findings indicate that Ritrutide improves body composition by greater fat mass reduction versus lean mass loss in people with type two diabetes.
And this shows that it really is the king. So let's look at the design of it. It was a phase two, again, double blind, parallel group, placebo controlled, all the markers of gold standard. Is actually conducted at 42 medical centers in the US, included a three week screening, a 36 week treatment, and four week safety follow-up. The participants were 18 to 75 years old with type 2 diabetes. The A1c ranges were 7 to 10.5%. They had to have a stable body weight for three months before this and the BMI of 25 to 50 kilograms per meter squared.
And basically what they were given is a once weekly subcutaneous placebo. Man, I always wonder that in these studies, like how disappointing would that be to be a type two diabetic that's obviously overweight and get the placebo thinking that you might be getting, Man, that just sucks. But they had Dulaglutide, which is just a really old GLP-1. Then they have Reda at 0.5 milligrams. They had Redat at four milligrams, with a two milligram initial dose. And Red at at 4 milligrams with the four milligram, initial does. The had red at eight milligrams was a 2 milligram.
Initial dose, they built up to eight, milligrams then they red a at an eight milligram dose with four, milligram additional dose that they build up, to a, and had read at a 12 milligram does, so it was double blind, double dummy design. So at baseline and week 36, sub-study participants had whole-body composition DEXA scans on Hologic or Lunar DExA scanners with total body composition capabilities. So this segments the body into head, arms, trunk, and legs using the DEXTA software. And what they looked at was the percent change in total fat mass versus dual glutide, the changes in body weight, the changes in total lean mass,
and then the change in android visceral fat mass. Which I think is one of the more interesting data points we'll see in this study. So just a brief overview, 534 screened, 281 participants enrolled, 189 sub-study participants, 155 baseline DEXA scans, 103 completed treatment with DEXT scans at week 36. Here's the total fat mass reduction. Let's look at this. So the percent reduction from baseline in total, fat, mass at week 36. Well, with red true tide 0.5 milligrams, we had a 4.9% reduction in fat mess.
Basically that means if you had 100 pounds of fat mask, you would have lost 4 point nine or five pounds fat math. This was not statistically significant versus placebo. Although I think it does prove the case that You can use pretty small doses of red trutide and still incur some fat loss, which is pretty cool. Especially if you're already lean and you just want that little edge. Now we have red Trutite four milligrams, jumps substantially here. We have 15.2% reduction in fat mass. This was significant versus placebo. So over 10.7% greater than placebo, Red true tide, eight milligrams, so 26.1% reduction of fat mass, which was obviously very significant versus placebo
over 21.6% significance over placebo. And then red true tied 12 milligrams. Very interesting here. 23.2% reduction in fat mass. So the 12 milligram people lost less fat than the 8 milligram. What does that mean? I don't know. Other than that fact that maybe red at 8 milligrams is kind of a sweet spot. Now again, with these eight milligrams ones, they actually were brought into that dose.
I think they either started at two or started a four milligrams. So did that have something to do with it? It's scaling up the dose over time actually accelerate the fat loss. I don't know, but I think this is a very, very interesting finding to see that the eight milligram group had more reduction in fat. And you can obviously see the chart right here than the 12 milligram. So again, was it just the people? I mean, maybe, you know there was 18 in the 8 milligram and 14 in 12 milligrams. Maybe it was the amount of people that they had in those groups.
But I think it's interesting nonetheless. So let's look at this from a total body mass. They list this in kgs, but Let's look at total body mass. So red, a 0.5 milligrams, 2.6 kilogram reduction after 36 weeks, red a four milligrams 9.50 kilogram, reduction red at eight milligrams 16.8 kilogram. Reduction 12 milligrams 17.55 kilogram production. And then the doula glutide only 08 kilograms and the placebo 2 01 kilogram so people's placebo actually lost less than do the good tide,
which for the confirms that do look good. Tide would be worthless at least for fat loss. So RETA 4-milligram and higher doses were superior to both placebo and dual-glutide in these measures. So when we look at total lean absolute change, so LSM, lean mass change. Absolute change in week 36. The Reta had 0.4 kilograms loss of lean-mass. Rета 4 milligrams had 3.1 kilograms of lead mass loss.
Reda 8 milligrams at 6.5 kilograms lead-mass loss, right at 12 milligram had 6.4 kilograms of lean mass loss to the glutide had an increase in point four and placebo had a decrease in 0.6. So interesting there again, we look at basically muscle mass lost that the eight and 12 were exactly the same of the amount of muscle that was lost. So does more always mean better? It would lead us to believe in this case, no, at least at that eight milligram range in the case of a study.
Again, take it with a grain of salt, right? But let's look at this visceral fat mass loss. I thought this was pretty cool. Right at 0.5 milligrams, 3.6 reduction in visceral fat bass. That's not nothing, especially when we're talking about viscera fat, which is like kerosene to our body. the most damage to our body having visceral fat on, at too high of a level. Red at four milligram, 19.1% reduction in visceral fat mass, pretty cool. Right at eight milligram 29.4 reduction of viseral fat and then red at 12 milligram 31.40% percent reduction and viscera fat.
So you see here the 12 milligrams at least the four extra milligrams got them an additional 2% production in the viscereal mass. But even at the four milligram, that's pretty substantial to lose 20% of your residual fat. And what I always reiterate with these is that most of these people, they're not changing anything. They're changing what they eat, their diet, not going to the gym, They are not doing anything to change. So imagine how much better it would be. The reduction of up to 9.1% with Reddit TrueTight 8 mg vs.
Paslebo in the trunk to leg ratio. This ratio is associated with cardiovascular disease risk factors including type 2 diabetes. non-alcoholic fatty liver and increased triglycerides. And then the reduction of the Android to gynoid ratio of 3.6% with red true tight, eight milligram versus placebo, which is also a strong cardiovascular risk indicator. So what this tells us is that red may preferentially reduce visceral fat,which is thought to contribute to cardiovascular risks or inflammatory adipokine secretion.
I would say that's a definite fact. It's not thought to, but it is pretty cool what it's doing to visceral fat. So we have this idea of the fat loss index and this is something else they looked at in the study. This is defined as a fat mass loss divided by total fat, mass, loss, plus lean mass lost multiplied by 100 to yield a percentage, a percent scale. Basically it just describing the proportion of weight reduction due to fat and important metric for the quality of rate reduction. What we like to see is an estimated 60 to 80% of weight reduction is fat mass, while only 20 to 40% is lean mass.
And obviously we're minimizing the amount of lean mask and we are maximizing the fat mask. When we looked at the 48 milligram groups, the mean fat loss index was 64.6%, meaning they lost 65% fat, 35% muscle, and the median was 67.8%. So the red F4 milligram had 69% percent fatloss, 77% median. The eight milligram has 62% loss. 62.8% median and the 12-milligram had 62% loss as well with 64% medium.
So what does that say? The smaller dose caused less muscle loss. Interesting school of thought for microdosing smaller doses. And again, eight versus 12 milligrams, they kept the same amount of fat loss and this proportion was the Same. It's a very interesting and I'd like eight to 12 milligram as you see. So when we look at this versus other treatments, semaglutide actually had more muscle loss. So this study, the mean across all of them was 64.6%. Semagglutides was 2.4 milligrams was 60%. Seemag glutide at one milligram was also basically 60%
interesting here. If you pull data from participants receiving five, 10, and 15 milligrams of trazapotide, fat loss index was 74%. So that means that at least in this case, from the data that they're saying, there was a higher proportion of fat lost from trisapatite than it was retitrutite. Again, small sample size, hard to say like which one's better or which ones not, but I think it's a case that like retritrutitite, maybe we just don't throw it all out wholesale because at this in case.
Now, granted, these were higher doses. So 5, 10, and 15 of trsapatites are higher than 4, 8, 12. of retitrutide, so interesting nonetheless. And then bariatric surgery had 74%. So retritrutidemia, a similar fat loss index compared to other pharmacotherapies suggesting does not cause disproportionately mass loss despite greater overall weight reduction. I think that is really the key here is that retrutides The proportion of fat to muscle loss is the same as all these, but it's creating greater total loss.
So even though it's creating greater total loss, we're not necessarily like proportionally losing more muscle as a part of that, which I think is very, very important as takeaway. So I thought this was interesting just to throw in the safety profile. Thankfully, no deaths occurred. GI events were most frequently reported and there were serious adverse events in eight participants out of the study. Fatigue occurred in 10% of people receiving four milligrams, 12% receiving eight milligrams and 3% received 12 milligrams.
And then we had nausea in 17% of the participants, diarrhea in 13%, decreased appetite in 11%. Kind of interesting. You would think it would be more constipation at 9%, COVID-19 in 7% and vomiting in 6%. So if you'd have those side effects from using your RETA, there you go, you're right in line with probably some of numbers. So just to close out too, we've got the GLP-1 receptor. like Lyric Glutide and Semiglutides have been approved for obesity management. We have Terzapotide, which is the dual GIP-GLP receptor is also approved obesity, but the glucagon receptor, is probably where all of this is coming in.
It's been shown to reduce food intake and diminish hunger. Acute glucogon infusion results in increased resting energy expenditure and the concern of muscle wasting with chronic glucagon receptors activation due to the effects on amino acid metabolism, but this study proved that at least as it stands now, it looks like we might not have to worry about that. So it's pretty cool. Obviously, this was a small study and we looked at multiple doses of ritrutide over a short window.
Again, there's just always going to be limitations. And what I like to think of this as is using this to inform our understanding of how this works. One of the main takeaways, honestly, I can say from this is that like, wow, if we look at eight versus 12 milligrams, 12 is not always necessarily better than eight. Like it seemed like eight was kind of a sweet spot, again, amongst this population of people. Retrotide significantly improved total fat mass reduction compared with placebo. The proportion of lean mass loss to weight loss was similar to other obesity treatments, which provides reassurance that a greater proportion lean-mass
is not lost with RETTA despite the overall increased weight-loss. So Rettas effects on visceral fat and fat distribution also likely have cardio metabolic effects, which means that it will probably continue to go through phase three trials and get approved. And obviously this was funded by Eli Lilly. So shout out to them, pay homage and respect to Eli Lily, right? Well, you can probably imagine how I feel about that, but that is it for the slides. And that is the review of the newest study out on Reddit True Tide, which includes those DEXA scan results.
So pretty fascinating. I think one of their takeaways from this is that more is not always better. When we look at all of these GLPs, there is likely a sweet spot, depending on your current body weight and how much you need to lose, to which you can maximize the results, and what I it's cool about this, is Retta, so far, from a data standpoint, It cannot be touched for the amount of weight it is helping people lose, but the question still remained until the study was that a good thing because were they losing more muscle than other
therapies alone? So at least as it stands right now, With the exception of that TrueTide data point, it seems to cause better total body weight loss, but you still retain as much muscle as you would on some of those other therapies, which I think is pretty cool. So again, not that those of us in the know didn't already know this, But Redis still looks like it is going to be king, at least until something else better comes along. I'll just close out with, I Think by the time that Redi True Tide gets approved, Knowing what I know about what's in the pipeline,
there will likely be stuff that is even better than red trutide, especially when we look at muscle maintenance, preservation slash growth alongside of something like red true tide. So stay tuned for more. It looks like it's going to be really, really cool. What happens over the next 12, 18 months. But that's all I have for this one. Again, I just like to close out. Thank you from the bottom of my heart to everyone that supports the channel. I'd love to hear your feedback on videos like this. If you like me doing a breakdown and deep dive of the study, there's a lot more where this came from. There's something new, but I thought it was something worthwhile to talk about.
Like I knew this in much more detail and depth in the future. So I look forward to your. And comments on this, one, thank you guys so much from bottom. My heart is a blessing privilege and honor to get to do what I do every day.
