The Peter Attia Drive - June 29, 2026


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

Hosted by
Peter Attia
#397 ‒ Endometriosis and adenomyosis： diagnosis, fertility, reproductive aging, and emerging treatments ｜ Renato Tomioka, M.D., Ph.D. Building strength and muscle mass： how to optimize training, nutrition, and more for longevity (AMA #71 rebroadcast)

Episode Stats


Length

9 minutes

Words per minute

165.83

Word count

1,635

Sentence count

71


Summary

Summaries generated with gmurro/bart-large-finetuned-filtered-spotify-podcast-summ .

In today's AMA, we look at the effects of GLP-1 agonists like Ozempic, Wagvegetide, and Zepedrone on muscle mass loss, and how they differ from weight loss by other means.

Transcript

Transcript generated with Whisper (turbo).
Hosts, guests, and mentioned names generated with spaCy (en_core_web_sm), reconciled against Wikidata.
00:00:00 Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.
00:00:15 I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access
00:00:20 the AMA episodes in full, along with a ton of other membership benefits we've created,
00:00:24 Or you can learn more now by going to peteratiyamd.com forward slash subscribe.
00:00:30 So without further delay, here's today's sneak peek of the Ask Me Anything episode.
00:00:38 Welcome to Ask Me Anything AMA episode 86.
00:00:43 In today's AMA, we're going to look at the effects of GLP-1 receptor agonists.
00:00:47 So these are drugs like Ozempic, Wagovi, and ZepBound.
00:00:50 But specifically, we're going to look at the impact they have on muscle.
00:00:54 We're going to talk about how much lean mass people actually lose on these drugs and how
00:00:58 that compares to weight loss by any other means.
00:01:01 We're going to define exactly what lean mass is and how loss of lean mass on DEXA can actually
00:01:07 mislead us, how these drugs impact bone mass and fracture risk, the all-important effects
00:01:13 of these drugs on strength and physical function, which probably should be the most important
00:01:17 metric, the effect of these drugs on different fat depots across the body, who's at most
00:01:22 risk for lean mass loss, how to maintain muscle and bone strength on these drugs, and the initial
00:01:30 insights of the effects of redditrutide, which is a drug I'm sure many of you have heard of as
00:01:35 it's making its way through the peptide cesspool at the moment, but nevertheless will be an FDA
00:01:42 approved drug in the not too distant future. And so people have lots of questions about how will
00:01:47 redditrutide affect weight loss, but specifically its impact on muscle mass as well. So without
00:01:53 further delay, I hope you enjoy AMA number 86. Peter, welcome to another AMA. How are you doing?
00:02:04 Very well, thank you. Awesome. So for today, we are going to talk GLP-1 agonist. And we did our
00:02:13 first episode on this about five years ago it was you and bob and back then no one was really paying
00:02:19 attention and no one really cared about that episode and then about a year and a half later
00:02:24 we did a second episode on them and all of a sudden people really started to care and so
00:02:29 thinking back at this what do you think it was about that second episode that got so many people's
00:02:35 attention on this i mean if i were to think about it through the the arc of the story of these drugs
00:02:42 I think it was obviously the impact on weight loss.
00:02:45 I mean, my first foray into GLP-1 agonists clinically was in 2014.
00:02:52 So, you know, 12 years ago, I started experimenting with liraglutide in patients, found it relatively
00:03:00 uninspiring, and for that reason, given the cost and the logistics, kind of abandoned
00:03:05 it.
00:03:06 And I think when we did our first episode, we were already seeing the effects of semaglutide
00:03:11 and how different it was. This was now the third generation of GLP-1 agonists. And we realized
00:03:17 internally, frankly, I think by, I recall it being in the fourth quarter of 2020,
00:03:24 that this was a step function change from the first two. And I just suspect in the answer to
00:03:29 your question that I think there's a tight lag between when the public sort of came to realize
00:03:34 that. Of course, the implications of that were that this was a drug that went from being kind
00:03:40 of a niche diabetes drug to a drug that had far more appeal because it was now for the first time
00:03:49 being looked at for weight loss in a non-diabetic. And so that kind of changed everything.
00:03:56 And at the time, the FDA was really just looking at weight loss. They weren't looking at body
00:04:02 composition. And so I think that was the beginning of the story. Just to kind of double
00:04:07 quick on that. When you started to use these a little more, what were you seeing and what kind
00:04:15 of jumped out that could have been problematic? Well, you know, what we saw in the early trials
00:04:19 and I think what we were seeing clinically five and a half years ago was that people who were
00:04:27 losing a lot of weight seemed to be losing much more lean mass than we normally saw in people
00:04:36 who were going about weight loss using the normal variations of caloric restriction or
00:04:41 dietary restriction or even time restriction, although there's a bit of an asterisk I could
00:04:45 put there. And it was almost a one-to-one ratio, which meant that if a person lost 10 pounds,
00:04:52 five of them would be fat and five of them would be lean as it's characterized on DEXA.
00:05:00 And so that's pretty relevant, right? So if you're going to lose 10 pounds and half of it's lean and
00:05:06 half of it's fat. That's very different than if you're going to lose 10 pounds and eight of it is
00:05:09 fat and two of it is lean. So we were using DEXA scans, but obviously you could even clinically
00:05:17 just look at people and see that something wasn't right with this form of weight loss.
00:05:21 And it seemed like around that time, that kind of became a large part of the discussion,
00:05:27 kind of outside in the media. And there was a lot of stories about these drugs and some of
00:05:33 warnings, correct? Yeah. A lot of scientific papers began to raise that concern. And I think
00:05:39 that's very good in terms of raising public awareness about the potentially important side
00:05:43 effects of these drugs. I think there's also been some fear mongering and speculating beyond what
00:05:49 the data have shown. And I think I would add to that, that as we learned the manner in which the
00:05:57 drugs are used and the manner in which the patients are counseled around the other modifiable
00:06:04 behaviors, particularly with respect to their nutrition and exercise, can change the outcomes.
00:06:10 So you also have to be careful that you don't over-interpret what you see in clinical trials,
00:06:16 which are average homogenized data, when you don't have insight into how those patients were
00:06:23 necessarily counseled. So it's, you know, it's valuable to have that information, but you also
00:06:28 don't want to be paralyzed by it and you don't want to discourage other doctors or patients
00:06:33 from kind of experimenting with how to get better results than what the clinical trials showed.
00:06:39 Yeah. And so now that we're a few years past that, what updates do we have around the story of
00:06:46 GLP-1s and muscle loss?
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