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

0:00Hey, everyone. Welcome to a sneak peek, ask me anything or AMA episode of the drive podcast. I'm your host, Peter Atiyah. 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 peteratiyahmd.com forward slash subscribe.

0:30So without further delay, here's today's sneak peek of the ask me anything episode.

0:38Welcome 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, Wagovi and Zep bound, 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

1:13drugs 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 retitrutide, 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

1:43not too distant future. And so people have lots of questions about how will retitrutide 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 are you doing? Very well. Thank you. Awesome. So for today, we are going to talk GLP one agonists. And we did our first episode on this about five years ago,

2:15it 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, 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 one agonists clinically was in 2014. So that, you know, 12 years ago,

2:54I started experimenting with lira, 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 semaglutide and how different it was. This was now the third generation of GLP one agonists. And we, 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

3:27two. And I, 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, 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, you know, kind of changed everything. And at the time, you know, the FDA was really just

3:59looking at weight loss. They weren't looking at body composition. And so, you know, I think that's sort of, that was the beginning of the story. 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? 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

4:30losing 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

5:03to 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, is lean. So we were using DEXA scans, but obviously you could even clinically just look at people and see that, 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?

5:34Yeah. 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 fear mongering 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 modifiable behaviors, particularly

6:05with 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, 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 of experimenting with how to get better results than what the clinical trials showed.

6:39Yeah. And so now that we're a few years past that, what updates do we have around the story of GLP-1s 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 premium member. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members. And in return, we offer exclusive member only content

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