The Peter Attia Drive - #398 ‒ AMA #86: GLP-1 RAs and muscle loss: new data, better questions, and how to preserve muscle during weight loss

Episode Date: June 29, 2026

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this "Ask Me Anything" (AMA) episode, Peter explores the effects of GLP-1 receptor agonists—including drugs such as Ozempic, Wegovy, and Zepbound—with a particular focus on their impact on muscle. He examines how much lean mass people actually lose during treatment and how those changes compare to weight loss achieved through other methods, while explaining why measurements of lean mass on DEXA scans can sometimes be misleading. Peter discusses the effects of these medications on bone mass, fracture risk, strength, and physical function, highlighting why functional outcomes may be more important than body composition metrics alone. He also explores how GLP-1–based therapies affect different fat depots throughout the body, identifies who may be most vulnerable to muscle loss, and outlines practical strategies for preserving muscle and bone health while using these medications. Finally, Peter reviews early insights into retatrutide, a next-generation weight-loss therapy, including what current evidence suggests about its effects on weight loss and muscle mass. If you're not a subscriber and are listening on a podcast player, you'll only be able to hear a preview of the AMA. If you're a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #86 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The evolution of GLP-1 receptor agonists from diabetes drugs to breakthrough weight-loss therapies [1:45]; Early concerns about lean mass loss with GLP-1 receptor agonists and the limitations of clinical trial data [3:45]; How newer research has changed the understanding of lean mass loss on GLP-1 receptor agonists and why DEXA measurements can misrepresent muscle loss [6:15]; Comparing lean mass loss across semaglutide, tirzepatide, and traditional weight-loss interventions [10:30]; Comparing lean mass loss from GLP-1 receptor agonists with bariatric surgery, and whether these drugs cause muscle loss beyond normal expectations from substantial weight loss [13:15]; The limited evidence regarding the timing of lean mass loss during GLP-1 therapy and the implications for exercise and nutrition strategies [16:00]; Body composition changes after stopping GLP-1 receptor agonists: weight regain, fat regain, and lean mass recovery [17:45]; Why lean mass measurements are an imperfect proxy for muscle health and function [21:45]; The effects of GLP-1 receptor agonists on bone mineral density, fracture risk, and the importance of resistance training [23:00]; Do GLP-1 receptor agonists directly cause muscle loss or simply mimic the effects of calorie restriction? [26:00]; Why strength and physical function often improve despite lean mass loss on GLP-1 receptor agonists [28:00]; Who is most at risk for lean mass loss during GLP-1–induced weight loss? [34:45]; Intramuscular fat (IMAT), DEXA limitations, and the challenge of measuring true muscle loss [37:00]; Preserving muscle while losing weight: resistance training, protein intake, and emerging research on preserving muscle during GLP-1–induced weight loss [39:00]; Resistance-training principles for preserving lean mass during GLP-1–induced weight loss [43:45]; Managing side effects and prioritizing protein intake while training on GLP-1 receptor agonists [46:15]; Retatrutide: early evidence on its effects on weight loss, lean mass, and muscle function, as well as the limitations of the data being collected in ongoing clinical trials [48:00]; The risks of using gray-market retatrutide before FDA approval [52:15]; Key takeaways [54:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to a sneak peek, Ask Me Anything or AMA episode of the Drive podcast. I'm your host, Peter Atia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to peteratia md.com forward slash subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything, AMA, episode 86. In today's AMA, we're going to look at the effects of GLP1 receptor agonists. So these are drugs like Ozempic, Wagovi, and Zepbound. But specifically, we're going to look at the impact they have on muscle. We're going to talk about how much lean mass people actually lose on these drugs

and how that compares to weight loss by any other means. We're going to define exactly what lean mass is and how loss of lean mass on DECSA can actually mislead us. how these drugs impact bone mass and fracture risk, the all-important effects of these drugs on strength and physical function, which probably should be the most important metric, the effect of these drugs on different fat depots across the body, who's at most risk for lean mass loss,

how to maintain muscle and bone strength on these drugs, and the initial insights of the effects of Retta Trutide, which is a drug I'm sure many of you have heard of, as it's making its way through the peptide cesspool at the moment, but nevertheless will be an FDA approved drug in the not too distant future. And so people have lots of questions about how will Reda-Truthide affect weight loss, but specifically its impact on muscle mass as well. So without further delay, I hope you enjoy AMA number 86.

Peter, welcome to another AMA. How you doing? Very well. Thank you. Awesome. So for Today we are going to talk GLP1 agonist. And we did our first episode on this about five years ago. It was you and Bob. And back then, no one was really paying attention. And no one really cared about that episode. And then about a year and a half later, we did a second episode on them.

And all of a sudden people really started to care. And so thinking back at this, what do you think it was about that second episode that got so many people's attention on this? I mean, if I were to think about it through the arc of the story of these drugs, I think it was obviously the impact on weight loss. I mean, my first foray into GLP-1 agonists clinically was in 2014. So, you know, 12 years ago, I started experimenting with Lira-glutide in patients, found it relatively uninspiring. And for that reason, given the cost and the logistics kind of abandoned it. And I think when we did our first episode, we were already seeing the effects of semi-glutide and how different it was.

This was now the third generation of GLP-1 agonist. And we realized internally, frankly, I think by I recall it being in the fourth quarter of 2020, that this was a step function change from the first two. And I just suspect in the answer to your question that I think there was just a, there's a tight lag between when the public sort of came to realize that. Of course, the implications of that were that this was a drug that went from being kind of a niche diabetes drug to a drug that had far more appeal because it was now for the first time being looked at for weight loss in a non-diabetic.

And so that kind of changed everything. And at the time, you know, the FDA was really just looking at weight loss. They weren't looking at body composition. And so, you know, I think that's sort of, that was the thing. the beginning of the story. Just to kind of double quick on that, when you started to use these a little more, what were you seen and what kind of jumped out that could have been problematic? Well, you know, what we saw in the early trials and I think what we were seeing clinically

five and a half years ago was that people who were losing a lot of weight seemed to be losing much more lean mass than we normally. saw in people who were going about weight loss using the normal variations of of caloric restriction or dietary restriction or even time restriction, although there's a bit of an asterisk I could put there. And it was almost a one-to-one ratio, which meant that if a person lost 10 pounds, five of them would be fat and five of them would be lean as it's characterized on DEXA. And so that's that's pretty relevant, right? So if you're going to lose 10 pounds, and half of its lean and half of its fat, that's very different than if you're going to lose 10 pounds and 8 of it is fat and 2 of it is lean.

So we were using Dexa scans, but obviously you could even clinically just look at people and see that something wasn't right with this form of weight loss. And it seemed like around that time, that kind of became a large part of the discussion kind of outside in the media and there was a lot of stories about these drugs and some of the warnings, correct? Yeah, a lot of scientific papers began to raise that concern, and I think that's very good in terms of raising public awareness about the potentially important side effects of these drugs. I think there's also been some fearmongering and speculating beyond what the data have shown. And I think I would add to that that as we learned, the manner in which the drugs are used and the manner in which the patients are counseled around the other moderated, the manner in which the defiable behaviors, particularly with respect to their nutrition and exercise, can change the outcomes. So you also have to be careful that you don't over interpret what you see in clinical trials,

which are, you know, average homogenized data when you don't have insight into how those patients were necessarily counseled. So it's, you know, it's valuable to have that information, but you also don't want to be paralyzed by it and you don't want to discourage other doctors or patients from kind experimenting with how to get better results than what the clinical trials showed. Yeah, and so now that we're a few years past that, what updates do we have around the story of GLP ones and muscle loss? Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a

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