Hey everyone, welcome to a sneak peek. Ask me, anything or am a episode of the drive podcast? I'm your host Peter, a TIA 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 Peter attea, m.com forward, slash
subscribe. So without further delay, here's today's sneak peek of the ask me. Anything
episode.
Welcome to ask me, anything AMA episode 64. And once again, joined by my co-host and extension, in today's episode, we cover a topic that we've addressed in the past, but has continued to gain significant attention since we last spoke and that, of course, is the topic of glp-1, agonists. You may have heard of these drugs, those epic, and when jarrow, but we go much deeper into the
Now, given how these drugs have gained popularity and given how our knowledge on them has advanced probably nonlinearly since we last discussed them. We felt. It was appropriate to address many of your questions on these topics and what we've learned through our own experience with patients. In this conversation, we begin with a very quick background on what a glp-1. Molecule is how these drugs work and why they are finding so much utility today. We focus on what we now.
Now know about their long-term efficacy, which is longer than what we knew in the past, what we know about side effects and what we know about what happens when you stop taking these drugs, we also talked specifically about their effects on body composition. This is something we couldn't speak to from clinical trial literature before. But we now, in fact have that data, we talked about the role resistance training plays on these and we talked about the differences between the specific glp-1 receptor Agonist. For example, is one of the
To on the market today. Better than others. Talk about the role compounding pharmacies or playing. In this, we talked about orals versus injectables. What some other health conditions might be? That are amenable to treatment with these drugs and we talked about the types of glp-1 agonists or other receptor Agonist that are on the market and that appear to be promising and at least in one case potentially more promising. If you're a subscriber and want to watch the full video this podcast, you can find it on the show notes page.
Age. And if you're not a subscriber, you can watch the sneak peek at the video on our YouTube page. So, without further delay, I hope you enjoy. Am a number 64
here. Welcome to another am a, how you
doing doing? Very well. Thank you for having me.
I see. You're in a new location today. Do you want to let people know why? Well, after
some planning, we've decided to expand the look and feel and create a dedicated studio for
So excited to have our inaugural in studio podcast today.
For people who don't know, we used to transform your office, your actual work offer us into a studio, every time we recorded. So how much nicer is it to not have that done each week?
It's as much nicer as it is, when you have to stop having a weekly root
canal, that that's good. That's good. Much less noise going on from background from kids, or dogs or anything.
Any of that nature as well, through in the new studio, which is always good for today's AMA. It's actually funny because it's kind of a little inside baseball. How we do the podcast is usually there's anywhere from a 10 to 12 week, Delay from podcast, recording to release, just with how we work. But this one is going to be released first and then we're going to go back to the old Studio a little bit. And the release schedule, but not the recording schedule. And the reason why is we are covering
Topic today that we want to turn around and get out as quickly as possible because it seems It's a topic that changes more than almost anything else that we talked about, which is glp ones or I wasn't picked Rose Abbott. I'd you kind of name it as people have heard of them. And I actually look back because you and Bob first talked about this November 20 21 is when we really set up a sewed we did a follow-up March 20 23 and
I don't think there's been a topic that has had more change in terms of interest in that period of time than this. And I still, I said it. The last podcast we did this one too, is I remember the first time you in Bob talked about wanting to do a glp AMA? And I was like, I have no idea why we're doing this. It was the most technical thing, it made no sense. No one was talking about it and now, it seems like it's everywhere even since the last 18 months when we did the last one.
So much has changed and so in this one, we're going to cover everything as it relates to these, and we'll just go through piece by piece. And we'll do a little recap of how they work, but previous amas will be best if people want to go into detail there. We're not going to spend as much time. We're going to spend much more time on what we know about this now. And how this works the difference between the drugs compounded injection, what we know about weight regain, safety profiles, the fast few times, you talked about this.
This there just wasn't as much information as there is now, and so I think will be really interesting because I think it's also one where you maybe have changed your mind a little bit based on past conversations that we had. So it will be a really good one. I think it will be really interesting and with all that said, do you want to add anything before we start rolling into
it? Yeah, actually quite a bit of context. So everything you said just to add on to that, if there's one thing that I get a kick out of its, I'm scrolling on Instagram and I see a video of me talking about
Some Igloo tide from three or four years ago and I frankly don't even necessarily agree with what I was saying at the time and that's just the nature of how things work, our knowledge changes a lot. And so that's part of my motivation for wanting to talk about this yet again. Today it's that we know considerably more today than we did three years ago. But I also want to acknowledge all the things we don't know. So that's one point. I want to make second point. I want to make is there's at least earlier, generations of these drugs have been around for quite some time. So the very first time I ever prescribe the class of this drug was a
Drug called liraglutide, and it's almost exactly 10 years ago, it was in the fall of 2014 that I prescribe that to a patient, not a particularly effective drug. So it would be another six years before I would prescribe some Igloo, tied to a patient in the fall of 2020, and that was a totally different experience. That was, of course, I was epic before it had been approved for obesity. So yeah, I think I just have a lot of stuff I want to talk about, but to your point. There's no need to rehash stuff. We've gone through before, I think it was am a 29.
Where Bob and I did and very deep dive into the physiology of how these things work. And we really, probably spent maybe more time than we needed to explaining to people how the GI tract works and how GI hormones work. So, not going to do that here. Let's cut right to it. So these are a class of drugs that were initially developed for the management of type 2 diabetes and that was largely on the basis of the fact that these are a class of drugs that mimic a hormone called glp-1.
Agon like peptide one that stimulates the release of insulin from the pancreas. Which of course if you have type 2 diabetes as opposed to type 1 diabetes is one of the routes of trying to get around the disease. When a patient's pancreas is no longer secreting, sufficient insulin that would be one half of what you would try to do. Of course, there's other things you try to do is what you want to increase, insulin sensitivity, and of course, that makes it so that you don't actually need as much insulin to get the glucose into the liver and to the muscles.
So if the story ended there we probably wouldn't be talking about this. If the story ended with these are great drugs to help people with type 2 diabetes, which roughly speaking about 1 in 10 Americans have today, might not be talking much about it. If it was lowering hemoglobin A1c and things like that, I mean that would be very important. But again, it's why is this such a topic? The topic is because with some Igloo tide something happened that didn't happen before with liraglutide, which was not only
Did patients have an improvement in their hemoglobin A1c, but their weight dropped dramatically. And so that led to the obvious question, which is, should we be considering these drugs for weight loss and people who do not have type 2 diabetes? And of course, that was a question that was basically posed through a series of Trials, 3 years ago, in the answer turned out to be emphatically.
Yes, I don't think we need to get into the details, but what's the 1014 sentence version for people as a reminder on how these drugs actually work?
Let's start with the most important which is the pancreas. So as I mentioned a second ago, it's going to stimulate the release of insulin secretion and reduce glucagon secretion. So both of those are going to have a net effect of lowering blood sugar, and the jejunum, and the ileum, which are just parts of the small bowel, it's going to reduce gastric emptying and GI motility. So, it's slows absorption of glucose from the intestines and keeps the stomach full for longer which by the way might partially
Relate to some of the satiety benefits in the liver. It reduces hepatic, glucose production. So, of course, again, probably something like what metformin is doing their most, interestingly, potentially, and we'll talk more about. This is in the brain. It's probably stimulating Pro satiety circuits and then decreasing the activity of the circuits that drive appetite. And again, I would say that a few years ago when we talked about this, we really had no idea how much that was driving weight loss. I would say today we have a feeling that it's doing quite a bit Within.
Fat tissue itself, it's increase in glucose, uptake from circulation and increasing lipolysis, that's a bit counterintuitive because on the one hand that's taking glucose out of circulation, that kind of makes sense due to increase insulin sensitivity, but it's also counterintuitive because that should make a fat cell fatter. But, of course, by driving lipolysis, it's actually increasing the throughput on the back, end in the muscle. It's increasing glucose oxidation, so increasing the capacity of the muscles to oxidize glucose will include a really nice figure in the show notes that goes through.
This in more detail. So folks can see what's happening, there are lots of other things, it's doing that. I don't think I'll talk about now. I'm going to wait and talk about them when we get to organ specific questions. For example, what is it doing specifically in the heart? What is it doing in the kidney? These are topics of huge interest today
as we kind of mentioned. It's been about almost 18 months, 19 months since the last time we spoke about this topic and so back then there was a lot of unknowns. So we were able to speak about certain things, but then there was also just unknowns with how new these drugs were
And so what have we learned what's like a quick overview of what we know? Now compared to what we knew last time we did a deep dive on this.
Yeah there's a lot I mean I'll start with just the fact that when we last spoke about this we were talking really just about to drugs, we were talking about a drug called semi glue tide which again the brand name for that. The first one that people talked about was those epic. It was just rebranded as we go V for the Obesity indication as opposed to just type 2 diabetes and then we
Talk about another one called her Zappa tide, which is a slightly different drug. As we're going to see in a moment, a slightly better drug and a drug that works not just on glp-1 but also on Gip another hormone it goes. By the brand name Manjaro but that's the diabetes version soman djaro is 20's empathic, what it's obesity counterpart, which is called zap bound is to would go V honestly I can't keep track of all these names so I just can't sort of try to remember the actual generic name of it. Which is of course
Some ugly tied into his appetite today. We have another one that we will talk about. That is not yet approved but it's the one I think people are very interested in so big picture. What do we have today? Why would we talk about this again today? Well, we have much more safety data and obviously, one of the things that I think we should be very cautious about with any new drug, especially a drug that has this much penetration in the market is, we want to understand what's happening in post-approval surveillance. So just because a drug gets approved during what's called a phase 3 study.
It doesn't mean the FDA stops paying attention. It's their job to continue to pay attention. And you want to see more and more trials phase for trials, much larger trials, where you look to see is there something that's emerging as problematic that wasn't showing up in the smaller, phase 3 trials. So we're going to talk about that. We're also going to talk about just a longer tail on benefits. So what do we know about weight loss over a longer period of time? Does the individual become recalcitrant to the drug at some point in other
Do they lose weight for 12 months but then all of a sudden they just regain in the presence of the drug still being there. There's lots of types of drugs where that's the case, not necessarily for weight loss but where we sort of get resistant to the effect of the drug? I think, today, we have a much better understanding of how the drugs promote weight loss. So, in addition to the clinical studies that look at this, I think we have better mechanistic studies to have more insight into what is actually happening. One of the big unknown questions. When we reviewed this the last time was we just didn't have
Real data. There was one study that we were able to look at that. Looked at weight regain after stopping. So today we have not just those preliminary studies and insights but we have more data on that. I would also just add I had as I'm sure any Doctor Who prescribed these, I've more anecdotal evidence about what that might look like. I think another big thing, Nick that I spoke about in speculated about in the past was really around the changes in body composition and not just wait and I think I mentioned very specifically that in the phase three tiles, the FDA did not require
Our
body composition as part of the primary outcomes. So dexa scans were not done in those studies and body weight was simply the metric of interest. And of course, because we started doing dexa scans on people, we were seeing some pretty different things with respect to body composition, but the good news now is we can speak to that more from the standpoint of the data that are available. I think we can also say more about the role of exercise in both weight loss and weight maintenance. Again, something we didn't necessarily have any
Hard data on before and then of course we can talk about the differences in the approved drugs so we can say a lot more about some Igloo tide and turns appetite and we can also we're going to talk about a new drug that's in Phase 3. That's pretty exciting as well. Something that wasn't really going on last time at least to my knowledge but seems rampant today as the use of compounding pharmacies to formulate these and we're going to do a bit of a double click on that because people who have listened to the podcast or no doubt familiar with what compounding pharmacies are. And we covered that
A previous am a. We obviously made a point to make sure people understand The Good, the Bad and the Ugly of compounding pharmacies, I certainly don't want to sit here and say the compounding pharmacies are bad as a bit of a buyer beware and they're not all created equal. And so understanding what the role of the compounding pharmacy is in these drugs is important. Let me think, I would say it's we talked about new drug. We're going to talk about that. I think the other thing that I really want to focus on today is understanding the other health benefits associated with it. So if anybody's
Scrolling through their Google feed. You almost can't go a day, certainly not a week without something popping up as yet another benefit of this class of drug. So it's like, oh, it's just been discovered that not only are glp-1 agonists. And it usually won't say that I say, not only is those epic good for weight loss, but it's also good for treating your sleep apnea or it's good for preventing Dementia or all these other things. So kind of want to go through the state of the evidence on that and really get a sense of of the five to ten other.
Haitians that people are talking about how robust are the data. So I'm not going to bury the lead on this. The jugular question with all of these indications is going to be, is there a benefit of the drug above and beyond the two things that we know it's doing which is reducing weight and improving metabolic health and glycemic control. It shouldn't be a surprise that these drugs improve other metrics of health, because reducing weight and improving glycemic control, always improve health. The question is, are they doing them?
At a level beyond the nameplate affect another topic. That really, we weren't talking about it all three years ago was the role that these drugs had on addictions or addictive behaviors. And finally, I think the last thing I want to touch on today is reports. We've heard about where these medications, May indeed increase the risk of suicidal ideation again, we'll talk about that. But I think it's, I don't have a hard time saying right now for someone who doesn't want to wait till the very end of this podcast that the answer there might not
Satisfactory, in terms of the paucity of evidence, we have to point to that.
So I think with all that said, I think what we'll do is we'll just check off each one, one by one and just go through it all in that order. And so, I think, let's start with the first, which was what do we know more about the long-term safety hazard? Been any new studies, any new data that's given us any insight into that long-term nature of these drugs.
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, am a 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. Premium membership includes several
Benefits first comprehensive podcast show notes that detail every topic paper person and thing that we discuss in each episode and the word on the street is nobody's show notes, rival h s monthly ask me anything or AMA episodes. These episodes are comprised of detailed responses to subscriber questions. Typically focus on a single topic and are designed to offer a great deal of clarity and detail on topics of special interest to our members. You'll also get access
access to the show notes for these episodes. Of course, third delivery of our premium newsletter, which is put together by our dedicated team of research analyst. This newsletter covers a wide range of topics related to longevity and provides much more detail than our free Weekly Newsletter. Fourth access to our private podcast feed. That provides you with access to every episode including amas son's. The should be able you're listening to now. And in your regular podcast feed fifth the
Polly's, an additional member only podcast. We put together that serves as a highlight reel featuring the best excerpts from previous episodes of the drive. This is a great way to catch up on previous episodes without having to go back and listen to each one of them. And finally other benefits that are added along the way. If you want to learn more and access, these member only benefits you can head over to Peter a.t.m., d.com forward, slash. Subscribe. You can also find me on YouTube, Instagram and Twitter, all with the hand
Well, Peter at EMD you can also leave us a review on Apple podcast or whatever podcast player. You use this podcast is for General informational purposes only and does not constitute the practice of medicine nursing or other professional health care services, including the giving of medical advice. No, doctor-patient relationship is formed, the use of this information and the materials link to this podcast. Is that the users own risk. The content on this podcast is not intended to be a substitute for professional medical advice.
Diagnosis for treatment. Users should not disregard or delay in obtaining, medical advice from any medical condition they have and they should seek the assistance of their Healthcare Professionals. For any such conditions. Finally. I take all conflicts of interest very seriously for all of my disclosures in the company's I invest in or advise please visit Peter, a TM d.com forward slash about where I keep an up-to-date and active list of all
disclosures.
