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

**Peter Attia** (0:10)
Hey, everyone, welcome to a sneak peek, Ask Me Anything or AMA episode of the Drive podcast. I'm your host, Peter Attia. 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 peterattiamd.com/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 GLP-1 receptor agonists. So these are drugs like Ozempic, Wegovy 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 Dexa 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 Retatrutide, 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 Retatrutide affect weight loss, but specifically its impact on muscle mass as well. So without further delay, I hope you enjoy AMA number 86

**SPEAKER_1** (2:02)
Peter, welcome to another AMA. How are you doing? Very well.

**Peter Attia** (2:05)
Thank you.

**SPEAKER_1** (2:06)
Awesome. So for today, we are going to talk GLP-1 agonists. 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?

**Peter Attia** (2:38)
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, 12 years ago, I started experimenting with liraglutide 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 semaglutide and how different it was. This was now the third generation of GLP-1 agonists. And we realized internally, that 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 time 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, the FDA was really just looking at weight loss. They weren't looking at body composition. And so I think that was the beginning of the story.

**SPEAKER_1** (4:06)
Just to kind of double click on that, when you started to use these a little more, what were you seeing and what kind of jumped out that could have been problematic?

**Peter Attia** (4:17)
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 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 pretty relevant, right? So if you're going to lose 10 pounds and half of it's lean and half of it's fat, that's very different than if you're going to lose 10 pounds and eight of it is fat and two 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.