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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. Before you can learn more now by going to peteratia-md.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 GLP1 receptor agonist, so these are drugs like ozempic, wagovian, 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 dexia 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 redotrutide, 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, we'll be an FDA approved drug in the not-too-distant future. And so people have lots of questions about how will redotrutide affect weight loss, but specifically, its impact on muscle mass as well. So without further delay, I hope you enjoy AMA number 86. Dear, 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 GLP1 Agonists clinically was in 2014. So, 12 years ago, I started experimenting with Lyra Glutide in Patience, 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 GLP1 Agonist. And we realized internally, frankly, I think by, I recall it being in the same way as 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'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 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 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 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. 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 warrants, 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 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 with respect to their nutrition and exercise, can change the outcomes. So you also have to be careful that you don't overinterpret what you see in clinical trials, which are average homogenized data when you don't have insight into how those patients were necessarily counseled. So 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. 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 peak 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 and benefits above and beyond what is available for free. So if you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. 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