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


Episode Stats


Length

9 minutes

Words per minute

165.83

Word count

1,635

Sentence count

69


Summary

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

Transcript

Transcript generated with Whisper (turbo).
00:00:00.000 Hey everyone, welcome to a sneak peek, ask me anything or AMA episode of the drive podcast.
00:00:15.820 I'm your host, Peter Atiyah. At the end of this short episode, I'll explain how you can access
00:00:20.280 the AMA episodes in full, along with a ton of other membership benefits we've created,
00:00:24.900 Or you can learn more now by going to peteratiyamd.com forward slash subscribe.
00:00:30.600 So without further delay, here's today's sneak peek of the Ask Me Anything episode.
00:00:38.900 Welcome to Ask Me Anything AMA episode 86.
00:00:43.420 In today's AMA, we're going to look at the effects of GLP-1 receptor agonists.
00:00:47.440 So these are drugs like Ozempic, Wagovi, and ZepBound.
00:00:50.480 But specifically, we're going to look at the impact they have on muscle.
00:00:54.460 We're going to talk about how much lean mass people actually lose on these drugs and how
00:00:58.860 that compares to weight loss by any other means.
00:01:01.280 We're going to define exactly what lean mass is and how loss of lean mass on DEXA can actually
00:01:07.540 mislead us, how these drugs impact bone mass and fracture risk, the all-important effects
00:01:13.000 of these drugs on strength and physical function, which probably should be the most important
00:01:17.160 metric, the effect of these drugs on different fat depots across the body, who's at most
00:01:22.480 risk for lean mass loss, how to maintain muscle and bone strength on these drugs, and the initial
00:01:30.240 insights of the effects of redditrutide, which is a drug I'm sure many of you have heard of as
00:01:35.980 it's making its way through the peptide cesspool at the moment, but nevertheless will be an FDA
00:01:42.280 approved drug in the not too distant future. And so people have lots of questions about how will
00:01:47.920 redditrutide affect weight loss, but specifically its impact on muscle mass as well. So without
00:01:53.220 further delay, I hope you enjoy AMA number 86. Peter, welcome to another AMA. How are you doing?
00:02:04.880 Very well, thank you. Awesome. So for today, we are going to talk GLP-1 agonist. And we did our
00:02:13.400 first episode on this about five years ago it was you and bob and back then no one was really paying
00:02:19.660 attention and no one really cared about that episode and then about a year and a half later
00:02:24.340 we did a second episode on them and all of a sudden people really started to care and so
00:02:29.640 thinking back at this what do you think it was about that second episode that got so many people's
00:02:35.500 attention on this i mean if i were to think about it through the the arc of the story of these drugs
00:02:42.240 I think it was obviously the impact on weight loss.
00:02:45.360 I mean, my first foray into GLP-1 agonists clinically was in 2014.
00:02:52.140 So, you know, 12 years ago, I started experimenting with liraglutide in patients, found it relatively
00:03:00.120 uninspiring, and for that reason, given the cost and the logistics, kind of abandoned
00:03:05.680 it.
00:03:06.020 And I think when we did our first episode, we were already seeing the effects of semaglutide
00:03:11.900 and how different it was. This was now the third generation of GLP-1 agonists. And we realized
00:03:17.720 internally, frankly, I think by, I recall it being in the fourth quarter of 2020,
00:03:24.800 that this was a step function change from the first two. And I just suspect in the answer to
00:03:29.640 your question that I think there's a tight lag between when the public sort of came to realize
00:03:34.440 that. Of course, the implications of that were that this was a drug that went from being kind
00:03:40.560 of a niche diabetes drug to a drug that had far more appeal because it was now for the first time
00:03:49.320 being looked at for weight loss in a non-diabetic. And so that kind of changed everything.
00:03:56.880 And at the time, the FDA was really just looking at weight loss. They weren't looking at body
00:04:02.060 composition. And so I think that was the beginning of the story. Just to kind of double
00:04:07.480 quick on that. When you started to use these a little more, what were you seeing and what kind
00:04:15.000 of jumped out that could have been problematic? Well, you know, what we saw in the early trials
00:04:19.660 and I think what we were seeing clinically five and a half years ago was that people who were
00:04:27.220 losing a lot of weight seemed to be losing much more lean mass than we normally saw in people
00:04:36.640 who were going about weight loss using the normal variations of caloric restriction or
00:04:41.720 dietary restriction or even time restriction, although there's a bit of an asterisk I could
00:04:45.680 put there. And it was almost a one-to-one ratio, which meant that if a person lost 10 pounds,
00:04:52.820 five of them would be fat and five of them would be lean as it's characterized on DEXA.
00:05:00.240 And so that's pretty relevant, right? So if you're going to lose 10 pounds and half of it's lean and
00:05:06.560 half of it's fat. That's very different than if you're going to lose 10 pounds and eight of it is
00:05:09.840 fat and two of it is lean. So we were using DEXA scans, but obviously you could even clinically
00:05:17.280 just look at people and see that something wasn't right with this form of weight loss.
00:05:21.920 And it seemed like around that time, that kind of became a large part of the discussion,
00:05:27.880 kind of outside in the media. And there was a lot of stories about these drugs and some of
00:05:33.480 warnings, correct? Yeah. A lot of scientific papers began to raise that concern. And I think
00:05:39.360 that's very good in terms of raising public awareness about the potentially important side
00:05:43.820 effects of these drugs. I think there's also been some fear mongering and speculating beyond what
00:05:49.140 the data have shown. And I think I would add to that, that as we learned the manner in which the
00:05:57.220 drugs are used and the manner in which the patients are counseled around the other modifiable
00:06:04.660 behaviors, particularly with respect to their nutrition and exercise, can change the outcomes.
00:06:10.300 So you also have to be careful that you don't over-interpret what you see in clinical trials,
00:06:16.380 which are average homogenized data, when you don't have insight into how those patients were
00:06:23.420 necessarily counseled. So it's, you know, it's valuable to have that information, but you also
00:06:28.600 don't want to be paralyzed by it and you don't want to discourage other doctors or patients
00:06:33.020 from kind of experimenting with how to get better results than what the clinical trials showed.
00:06:39.320 Yeah. And so now that we're a few years past that, what updates do we have around the story of
00:06:46.120 GLP-1s and muscle loss?
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