Retatrutide Promises 28% Weight Loss (What About Muscle?) | Ep 477
Is retatrutide, the new triple agonist GLP-1, the next big thing in weight loss (or even rapid fat loss)?
That depends on how the drug works, what the results are, the reality between the headlines and the evidence, and what happens to your weight when you stop.
This episode breaks down retatrutide, the GLP-1, GIP, and glucagon triple agonist behind the largest weight loss numbers ever recorded in this class. It covers the Phase 2 obesity trial and the Phase 3 Triumph results, plus why cross-trial comparisons to semaglutide and tirzepatide deserve skepticism.
We examine the body composition data (or lack thereof), and why a bigger number on the scale just amplifies the stakes for muscle mass, weight regain, and the off-ramp. Especially relevant for adults over 40 who are taking, considering, or planning to come off a GLP-1.
Enroll in Eat More Lift Heavy, the 26-week coached program where adults over 40 build the nutrition and training skills to preserve muscle, lose fat, and manage their physique for life, including support for lifestyle changes needed while taking GLP-1s (and to come off them if desired).
Timestamps:
0:00 - Retatrutide and the biggest question for GLP-1 users
3:08 - How this new triple agonist works
4:46 - Phase 2 and Phase 3 weight loss numbers
5:38 - Cross-trial comparisons and their limits
6:23 - Fat, muscle, and what the trial did NOT measure
8:30 - Strength training over 40 and accelerated muscle loss
10:07 - Building the lifestyle (alongside using the drug)
14:10 - Resistance training and protein
16:00 - Rate of loss on a powerful drug like retatrutide
17:30 - The off-ramp when you stop
18:23 - Weight regain and body fat overshooting
22:03 - Retatrutide access and the gray market
24:11 - Bonus: 3-question test to keep your results
Episode Mentioned:
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Retatrutide and the biggest question for GLP-1 users
Philip Pape 0:00
There is a new weight loss drug in the headlines right now. It is a triple agonist called retatrit. Some people call it retatutride. And the numbers are the biggest that we've seen so far, up to 28% of body weight in the latest trial. So if you're on a GLP1 or you're thinking about one, you're probably wondering, does this change anything for me? Today I'm going to show you what the data shows, what it doesn't show, and one thing that this huge amount of weight loss is not actually going to fix, no matter how good the drug gets. And I'm not talking about muscle. Welcome to Wits and Weights, the show that puts a popular piece of fitness advice under the microscope, finds the hidden reason it doesn't work, and gives you the deceptively simple fix that does. I'm your host, certified nutrition coach Philip Pape. And a few weeks ago, we did a full episode on GLP1 medications as a category. The whole picture, miracle drug versus is it cheating, what the body composition data says, all that stuff, the science behind it. Today we're gonna get a little bit more narrow and very timely, very trendworthy because there's a specific drug, retatratide. And by the way, pronunciation can go both ways. Eli Lilly and their CEO call it retatrotide. A lot of people will say retatrutide, like semaglutide, because of some linguistic, you know, rules, let's say. I don't care. I'm gonna say retatrotide because a lot of the guys I follow call it that. It's been all over the news. The phase three trials came out, and the weight loss numbers are the largest ever recorded. I have some former clients and even current clients who have experimented with it on their own, not under my supervision, and report, you know, incredible results. There are things about it that seem to go above and beyond weight loss as well, potentially for liver fat and stuff like that. Uh, but I'm getting a lot of questions about it. People want to know, you know, is this something I should do? There's a lot of or consider, there's a lot of discussion in Reddit and in the body composition forums about like rapid fat loss. It's kind of an interesting, you know, designer approach to rapid fat loss among bodybuilders. Very interesting, uh, the way, the way it's being talked about compared to the other ones. And then, of course, there's the whole muscle loss issue, right? Which we'll address briefly, but you know, it's not gonna be the main thing here. I really want to do two things today. First, I want to separate what the data shows from what I think it means very deliberately with nuance. They're different things. A lot of the coverage in the news just smears all this stuff together. It's very surface level. And then I want to give you a framework, right? Not a hot take, just a framework. How do we think about this drug or any other drug that's coming down the pipeline? Because more are coming. I think retatrotide is not the last one. There's other drugs on the other side of the spectrum for what do you call it, you know, preventing muscle loss as well, that we're looking at, like myostatin blockers, et cetera. Then I want you to stick around to the end of today's episode. I'm gonna give you a 30-second self-test to tell you whether you've done what you need to do to keep the weight off after you stop a medication like this. And honestly, a lot of these things are things you should be doing regardless of that. But I think it's important to ask yourself these questions so that you could actually maintain your results.
How this new triple agonist works
Philip Pape 3:08
All right, let's talk about what this drug is retatrotide and the weight loss and all of that, because the mechanism is important. You've heard of semaglutide, that's osempic, that's wagovi, that's a single agonist. It hits one receptor, GLP1, that is a hormone that your gut releases that tells your brain that you're full. And then it slows down how fast your stomach empties. And by the way, side tangent, if you take, if you eat a lot of fiber, you're gonna get a lot of that naturally, just FYI. Okay. Then there's terzepatide, which is Manjaro and Zep bound. That's the dual agonist. It hits GLP1 and a second receptor called GIP. So that is two targets. And in the trials, it outperforms semaglutide on weight loss. And again, semaglutide, semaglutide, doesn't matter. Retatrotide is then the next step, which is a triple agonist. It hits GLP1, GIP, and then a third one, glucagon. And that's the interesting part. And I want to explain why. The glucagon is really interesting. The first two receptors, GLP1 and GIP, they work mostly on the energy inside, right? They turn down your appetite. But the glucagon piece, the third piece for retatrotide, is theorized to work on the energy out side. It acts on your liver and it's thought to increase energy expenditure and burn liver fat directly. So, in theory, you've got here appetite suppression on one hand and a bump in how much energy you're burning on the other. And we love talking about metabolism and how important that is. And that's why this could be so powerful. And so when you look at the numbers, it backs
Phase 2 and Phase 3 weight loss numbers
Philip Pape 4:46
it up. In the phase two obesity trial published in the New England Journal of Medicine, people on the highest dose of retatrotide lost 24% of their body weight over 48 weeks. So that's just less than a year. And it wasn't, it didn't plateau by that point. It was still going when the trial ended. And then the phase three trials came out, they call it Triumph 1. And the highest dose, they got 28%, but that was over 80 weeks. And then there was an extension group that had even more severe obesity and they got past 30% weight loss. So if we put it in context, semaglutide in in the big trial that we know about there got to people, got people to about 15%. Terzepatide got to 21, maybe 22%. And now we've got a drug flirting with almost 30%. So that is a huge amount of weight loss just from the drug. Now, a real important caveat that's going to apply to the rest of the episode.
Cross-trial comparisons and their limits
Philip Pape 5:38
The comparisons I gave you were like the 15 versus 21 versus 28%. These are across different trials, right? They're different people, different starting weights, different lengths, different decades of life, et cetera, which it means they're not head-to-head, which for practical reasons you could understand why. There are different drugs being tested under different, maybe different protocols and different groups and so on. So there's never been like a head-to-head trial for tatrotide against trusepatite, semaglutide. So when you see the comparisons, just you know, put a little skepticism on any of these claims because these are cross-trial comparisons. I don't know. That's just a caveat I thought I'd mention again, because we like nuance here. So that's the drug, that's how much weight loss. And now what we want to do is dig down a little bit deeper.
Fat, muscle, and what the trial did NOT measure
Philip Pape 6:23
So when you lose 28% of your body weight, the obvious question, I think this is potentially the most important question, right? Is what was the weight that you lost? Was it fat, was it muscle, and how much of each? That is what we care about on this show when we talk about body composition, health, physique, you know, muscle mass, is that when you lose weight, you want to lose body fat. You don't want to just lose weight. And when you look at the biggest trial, the one I mentioned in the New England Journal of Medicine, they didn't measure body composition. They did there's no DEXA scan, no lean mass data, no fat mass data. And it kind of floors me a little bit that they wouldn't measure those things because they're so focused on just weight loss, which I'm not saying weight loss isn't massively important for moving the needle for so many people when it comes to their health, because it is. I'm also not saying that it isn't helpful for the reasons why people struggle to lose weight, right? With like the food noise. Super important things. I get it. But when you hear retatrotide being talked about on body composition and bodybuilding forums and Facebook groups and whatever, and saying, hey, this is more muscle sparing, there's no evidence for that. There is zero evidence for that. It's the same as any other form of weight loss. You're gonna have to do the right thing to preserve your muscle, which is lift weights. Uh, you know, eat protein, yes, but mostly the training stimulus is what holds on to the muscle. And the the only retatrotide body composition data actually comes from a smaller group in a separate trial. It was a diabetes trial, and they did get DEXA scans. And guess what they found? The proportion of weight losses lean mass was similar to other obesity treatments. Not any better than it wasn't, it didn't protect their muscle mass or whatever. So just I want to get that out of the way right now because you may have seen that kind of misinformation online already. And if we look across the GLP1 drugs, when you don't strength train and you don't pay attention to protein, you can lose somewhere around a quarter to up to, in some cases, 40% of the weight is lean mass. Now, not all of that is muscle, that's lean mass. Some of it's water, some glycogen, some of it's your liver getting smaller, which is actually a good thing in this case, but a huge
Strength training over 40 and accelerated muscle loss
Philip Pape 8:30
chunk of it is muscle mass, right? The contractile, metabolically active tissue that we really, really love and care about. So if we think about the math, if retatrotide loses, you know, causes a loss of lean mass at the same proportion as the rest, but it takes you to a bigger total weight loss, then of course, the raw, absolute pounds of muscle you're gonna lose is even more in the same amount of time, right? Now, I again I mentioned like a former client who experimented with this, and we're at a place where you can only experiment with it until it's approved and available. And you know, he was lifting weights. So, of course, he got the benefit of the fat loss piece of it. The appetite side is obviously super important for a lot of people. And so just changing the energy in, and then now the potential energy out can be, of course, very powerful. And I just wanted to sit with this for a bit because it's super important, you guys listening. Most of you are in your 30s, 40s, 50s beyond listening to this show. We have a lot of women who listen to the show, probably two-thirds of the audience. If you're in your 40s or 50s, if you're going through perimenopause or past that, if you're already fighting the accelerated muscle loss that occurs with age, and that's why you're listening to the show because you want to lift weights, you want to have a better uh lifestyle, and you want to, you know, feel better in your body, you want to have better energy and function, then listen up, right? Because, you know, if your estrogen is dropping or testosterone's dropping, it's harder to build and keep muscle. Well, it's not harder to build muscle, it's harder to keep it if you're not building the muscle. Let's just put it that way, and you're at most risk of that accelerated muscle mass. Now you then go on to this drug and you're not already doing something to preserve that muscle. Now I think you can see the problem, right? So that's that's kind of the gist on retatrotide.
Building the lifestyle (alongside using the drug)
Philip Pape 10:07
And, you know, one thing I like to tell people is look, that doesn't preclude you from working on your lifestyle while taking these drugs. In fact, you need to, you have to work on the lifestyle. We help people with this all the time in what's called eat more lift heavy. And I know I talk about my program a lot, as you would expect, because it's our program and we bring you this content for free. And this is the way that we support the podcast and our business. But when you're on tursepatite, or in the future, I'm gonna see more people on retatrotide, there's an interesting phenomenon that happens. Your appetite is highly suppressed, right? And now you're starting to lose straight weight, and you maybe you're a little bit excited. Maybe you are lifting weights, but then you start to have issues because you sometimes you can't eat enough or you can't eat enough of protein, and you're not in touch with their hunger signals as much. And so now it's this weird limbo kind of you know, middle ground of, okay, do I titrate down a little bit as I'm building in the lifestyle? You know, some people have such severe appetite issues that they don't, it doesn't actually cause a concern. They could just stay on the drug and they can eat enough and they can, you know, lose fat and weight at the right glide path, let's say, while they're lifting and getting their protein locked in and all of that. But what we like to help people with is figure out from your own data, from your own hunger signals, from your food, how you're logging it, where the issue is. And just this, just the last couple of weeks, we have someone in the group who talked to their doctor and they say, you know what, we're gonna slowly get you off this drug because you may not need it anymore. You you're on Phillips program and something magical is happening to you. What's going on? He's like, Well, I'm lifting consistently. I'm tracking my food, I'm trying to get enough protein, I'm eating more fiber, and I'm losing weight, but I'm almost losing it too quickly. And I don't have enough appetite to eat the minimum that I need to eat to stay at the right level of fat loss. Isn't that crazy? So if you go to eatmoriftheavy.com, you'll learn all about what we do. Um, it's a very guided, structured approach over a six-month period where each week we drop a little nugget of knowledge to help you move forward. And it's not information, it's actually do this this week. Do this this week. And it helps you set the skills up for the tracking and the lifting and the eating and all the other things. And so if you're on GLP1 or, you know, a trazepotide or maybe or tatritide, you've got to have a structured approach to put in the lifestyle in parallel. And that's really my key message with any of this stuff when I talk about GLP1s. It's not that they're a shortcut or, you know, you didn't have the will to do it yourself or you didn't know how to modify your behavior. It's like, no, okay, you chose to use this tool for one reason or another because you needed it, wanted it, your doctor suggested it, you struggled with something, whatever. Doesn't matter. I don't care. That's great. You're a human being with your own struggles, like we all have. Now let's work to incorporate the lifestyle you need. It doesn't guarantee for you as an individual you're gonna completely come off the drug. You might have such massive food noise and emotional eating issues that it's necessary and helpful for that from a medical perspective. But for many, it helps you titrate down and sometimes get off of it completely or use it as a tool when you need to. And then from a budget perspective, it can be helpful because these things are darn expensive. So let's that that's kind of the climax of the episode. But, you know, the fix for retatrotide is the same fix for every other drug. There's no special GLP1 protocol. Don't get scammed into like a special GLP1 diet or GLP1 book. I do know a couple of folks in the industry who I respect who have come out with GLP1 protocols and I'm a little bit kind of cringe or I feel a little icky about it, right? Because it it's kind of like the preying on women who are in peri and postmenopause where your body's broken and it doesn't work anymore. And so I'm gonna fix everything for you. We need to balance your hormones. It's that kind of language, which I don't like. I'm perfectly fine saying, hey, if you're in perimenopause and your hormones are declining, now's the time to step it up and lift and learn to eat better for your body. But we would do that anyway, whether you're in perimenopause or not. But like now's the time to do it, but without preying on the fears. And I think the same thing goes here with like the GLP ones. You don't need a special protocol. What do you need
Resistance training and protein
Philip Pape 14:10
to do though? Okay, four pieces. Number one is absolutely resistance training. This is the biggest lever in your life for the rest of your life that has to be part of a routine. That has to be part of your routine. It's more important than cardio, probably more important than steps and movement. In fact, I would say it is because you have to do it. In other words, if you had to pick lifting or steps, I would pick lifting. Of course, it's not a mutually exclusive thing. I don't want you lifting and sitting around all day. We just did an episode about the sedentary lifter one or two episodes ago. So go check that out. But lifting is the number one lever because the stimulus for your muscles is the only thing that prevents muscle loss when you're losing weight, but also helps you preserve and build muscle even when you're not losing weight as we get old. So that's number one. Number two is having a certain minimum amount of protein. Now, the more and more I talk about this and the more evidence we find, we see that number one, the amount you need isn't a crazy amount. Okay. Yes, we talk about up to one gram per pound of protein, but the minimum is more like 0.6, 0.7. And if you're there, you are in great shape. You've got like 90, 95% of the benefits. Total protein for the day, 0.7 grams per pound of goal body weight is really the idea here. So if you're quite overweight and you're trying to lose weight, you don't have to quite get 0.7 grams per pound of your current body weight. It could be toward your target body weight. But don't pick a ridiculously, you know, 100 pounds less body weight, just something reasonable for the next, say, six months where you're gonna get to. So that's kind of the floor. And the problem when you're on a GLP one drug is your appetite is lower and protein is very, very filling. So if you are now bringing it up and you're on these drugs, that's where you might run into the wall of, oh my God, this is too much to eat. I mean, we see it all the time in eat more lift heavy. You come in and they're like, okay, I know I need to get this much protein. I
Rate of loss on a powerful drug like retatrutide
Philip Pape 16:00
even know what foods make it up, but I can't physically do it, Philip. I'm too full. How do I do it? Yeah, I've tried the shakes. Yeah, I've tried more frequency. Well, sometimes you just actually have to lower the drug dose. And that's a great problem to have if many of you see that as a place you want to get to. But protein's very, very important. Uh, number three is how quickly you are losing weight. So with one of these drugs, especially retatrotide, which is so powerful, you can lose weight faster than your body can handle without it losing muscle. And again, number one and two, training in protein are gonna massively mitigate that. But there is a cliff that you can go off of here where you're just losing way too fast. Now it depends on the duration. Depends on the duration. So this is why I think retatrotide comes up in the rapid fat loss discussions, which we're gonna do an episode on that topic pretty soon. Is that bodybuilders are like, okay, I'm gonna go on retatritide for like four weeks and I'm gonna lose a massive amount of weight, but I'm gonna keep my, I'm gonna do like a protein-sparing modified fast, and then I'm not gonna have the hunger. And you know what? I can't, I can't argue with the logic. I really can't argue with the logic. So the problem is right now is you can't get these drugs legitimately. And somehow people are talking about retatrotide as if it's special versus the other two. It's special in the sense that it has a third agonist that affects glucagon in your liver. That that's actually pretty cool. And that could move the needle in its own way. I totally acknowledge that. But it's not special in
The off-ramp when you stop
Philip Pape 17:30
terms of the weight, in terms of like the muscle mass preservation part. So just take that with a grain of salt. Okay, so that's a third is the rate of loss. And then the fourth piece is the off-ramp. What happens when you stop, not just on the drug, but even when you're not on the drug? What happens when you stop a fat loss or weight loss phase? Well, why don't we dig into that? Okay, so let's dig into that one for you guys, because I think that is important to sustaining your results. And I, you know, I keep mentioning our program, Eat More Lift Heavy, but my goal with that was to take what I've learned with me and my clients who get to sustain, who get to fire me and never have to come back again or hire another coach, is how the heck do I sustain my fat loss and stay lean for a life? If that is your goal. Now, many people they get lean and now they're like, okay, great, now I'm gonna go in a muscle building phase, pack on some more weight, but do it for the right reasons. But how do you maintain whatever you want to maintain? All
Weight regain and body fat overshooting
Philip Pape 18:23
right. So if we look at the drugs like semaglutide in the big trial for that, there was an extension part of the trial where they tracked people when they came off the drugs. And within a year, people regained two-thirds of the weight they'd lost. And then the metabolic improvements that came with the weight loss, blood pressure, blood sugar, those went back to where they started as well. And now, if you think about retatrotide, you're just ramping that hole up. You're you're just amplifying the that amount. You're losing up to 30% of your body weight, and say two-thirds of that comes back. You know, the bigger loss, the more there is to regain. And again, if you're not protecting your muscle and lifting weights, you're gonna regain mostly fat. That's called body fat overshooting. You're gonna be worse off than when you started. You're gonna have a higher body fat percentage than when you started, even if you're at the same weight, right? And the problem is these drugs, they do something powerful. They suppress appetite while you're on them, but they don't give you any specific skills, behaviors, or habit changes. They don't teach you how to eat, they don't teach you how to build lift weights or even to lift weights, they don't give you the skill of navigating weekends or vacations or stressful weeks, you know, without the the wheels coming off. Let's say, you know, the training wheels. It it completely takes over the appetite piece, which is great until it's not, and you realize you didn't do the things you wanted to do. And not only that, you you know, you may have lost muscle, et cetera, like we've already talked about a million times. So the deceptively simple fix, the premise of this show is this that the time that you're taking these meds, that is not, I'll say, the end goal. That is the window of opportunity where your appetite is quiet enough now, your food noise is quiet enough that you can build the skills while it's easy for you. And you're gonna need those skills later when it gets a little bit harder. And the funny thing is, when I say hard, when you build the skills while taking the drug, you actually make the hard moderate or you make the moderate easy. Does that make sense? Like now that you're having more protein, you're eating nutritionally or nutritiously, you have more fiber, you know how to track and how much you eat, you know how to lift, you're getting more steps and movement, hopefully. You have structure and planning around your food and your routine. All of that, you build those skills while taking the drug. Then when you come up, now you have the behavior. The drug gave you, you know, a lower appetite, but now when you get off it, you get to see what your true regulated appetite and hunger signals are. And you could do that in a titration way. You can slowly come off or you can go off big time. I I one of my earliest clients, she was like in her mid-60s, she hadn't lifted weights before. She took Ozempic for diabetes. And I saw this when we went into a fat loss phase. Her hunger was non-existent. I thought it was incredible. I'm like, okay, let's take advantage of this and keep the gas pedal down as aggressively as possible so you don't lose muscle. She was lifting three days a week. She was doing deadlifts, squats, all that fun stuff. First time in her life, doing amazingly. And then she went off the drug kind of cold turkey overnight while in a fat loss phase without me knowing. And then her next check-in, she's like, oh, I have a lot of hunger all of a sudden. Like, yeah, that makes sense because we hadn't gotten to the point of build finish building the skills, plus you came off a cold turkey, plus you did it while in a fat loss phase. So there's like three things stacking on top of each other. So my suggestion is to do one thing at a time, right? Build the skill, start to titrate, not be in a fat loss phase, and then come off. Something like that, right? And I'm not a medical doctor, it's not medical advice. This is just a suggested Approach that could be uh sustainable. Okay.
Retatrutide access and the gray market
Philip Pape 22:03
All right. So a quick word of caution before we wrap up on the science. Again, retatrotide right now, as I record this, is not approved anywhere, not by the FDA or anywhere, as much as you might trust the FDA or not. You can't get it at a pharmacy. The only legitimate way to take it now is in a clinical trial. So for the rest of you, taking it, buying it online from a peptide site, from a compounding source, just like with peptides, it's a Wild West. You are taking a risk. There's no guarantee of the dose, the purity, the safety. So please, I'm not your doctor, but the term gray market or black market applies here. And whatever risk tolerance that means to you, please take that to heart. Just take it to heart. That's all I can say. All right. Before we wrap up, remember, I'm going to give you three questions for 30 seconds. It tells you whether you've built what actually keeps the weight off. I'm going to give you that in just a second. But first, if you're one of my listeners who are taking these medications or you're considering taking them and you're worried about the off ramp and the lifestyle, man, that is what we help with in Eat More Lift Heavy. Go to eatmoreliftheavy.com. That is the whole design of it. The reason that it is 26 weeks long and not a quick fix or just a course. And it builds the behavior while you've got the appetite working in your favor. You've got two human coaches in there. Carol and I will take you through getting your nutrition dialed, getting strong. And then by the back half of the program, we start to hand the controls to you. In other words, you build independence. That is the off-ramp. We built it that way on purpose. That is the difference between losing weight and getting it back on and losing fat, getting lean, strong, healthy, feeling great, and staying that way. So if you want to be the person who still has their results a year, five years, 10 years after they stop, and you don't need to hire another coach again, go to eatmoreliftheavy.com and take a look. That's eatmoreliftheavy.com. And look, if you have questions, just reach out to me. It's Philip at witsandweights.com. Philip with one word at witsandweights.com, but go to eatmoreliftheavy.com.
Bonus: 3-question test to keep your results
Philip Pape 24:11
All right, here's a 30-second test you can run on yourself right now. It's three questions. I love these little quizzes at the end of these episodes. Question one, if the drug disappeared tomorrow, like if you didn't have access to these at all, do you have a nutrition plan that you're confident with right now, especially hitting protein? Do you even know how much of protein to hit and how to hit it and do it consistently? So that's question one. Question two, have you trained by lifting weights using resistance training at least twice in the last week, challenging your muscle, not just moving, but challenging and pushing each time in the gym? Question three, do you have a plan for when things get hard, like a vacation, a stressful week, the holidays, where your structure is there even when your motivation is not and everything is changing? If you answered no to any of these, that is a good sign that you might have trouble keeping your results. Those are skills. And again, this is whether you're on the medication or not. It's just very important because if you are on them now, you want to have these skills in place before you come off. That's just my opinion on that. The drug handles the appetite, but all of these other things handle your life and how you deal with this going forward. All right, until next time, keep using your wits, lifting those weights. And remember that a bigger weight loss on the scale is not the hard part. The skills that you build, that is the real story of success here. I'm Philip Pape, and I'll talk to you next time here on the Wits and Weights podcast.
