Direct Line April 2026: Stopping Ozempic and Lifting With Osteopenia

0:00 [SPEAKER_00]: Welcome back to the Barbell Medicine podcast. [SPEAKER_00]: I'm Dr. Jordan Faganbaum and this is the direct line our monthly podcast for our Barbell Medicine Plus subscribers. [SPEAKER_00]: In this episode we cover what exactly happens when you come off at GLP1. [SPEAKER_00]: A real plan for lifting with osteopenia.

0:15 [SPEAKER_00]: calcinex versus barbells for a woman in perimenopause, and a critical look at Dr. Gregor's daily dozen, also the dirty dozen, and why your strawberries are fine, as well as picking a bone with the orthopedic cost narrative around the spine. [SPEAKER_00]: All that plus the new ACSM resistance training standards, how to train the frail elderly and more, and to help us argue with your drunk uncle, your orthopedist, the environmental working group, and Sabrina Carpenter, it's the second most handsome Dr. North America, Dr. Austin Baraki, what's going on with?

0:43 [SPEAKER_01]: I do not know that I have such a diverse skill set as to take on all of those targets. [SPEAKER_00]: It's actually the same argument for each of them. [SPEAKER_00]: Have you tried carrying this? [SPEAKER_01]: That'll work. [SPEAKER_01]: All right, fair enough. [SPEAKER_01]: How are things going?

0:57 [SPEAKER_01]: Hectic, been in the hospital for a couple of days, and today was a particularly busy day. [SPEAKER_01]: Had about, I think, 16 in patients, and I saw with my team and managed to discharge about half of them, had an ICU transfer for a relatively rare diagnosis that needed more urgent management.

1:13 [SPEAKER_01]: So, yeah, a lot going on today. [SPEAKER_00]: Be busy, okay. [SPEAKER_00]: So, not enough to keep up with what's happening with Sabrina Carpenter, the Coachella Controversi, [SPEAKER_01]: My wife and I did couchilla before I started in the hospital. [SPEAKER_01]: So I just started on Monday.

1:26 [SPEAKER_01]: So we did sit on the couch and watch some of the main acts. [SPEAKER_01]: And that was one of them. [SPEAKER_00]: Okay. [SPEAKER_01]: Some of the contrast between some of those headliners in terms of, let's call it the effort that they put into their show was amusing to us. [SPEAKER_00]: I mean, I just hope that at some point I can just get on stage and play a YouTube playlist.

1:40 [SPEAKER_00]: Like just our greatest hits, maybe, you know? [SPEAKER_00]: I don't know. [SPEAKER_00]: Yeah. [SPEAKER_00]: All right. [SPEAKER_00]: Well, let's start off here. [SPEAKER_00]: We're going to start with GLP1's no surprise. [SPEAKER_00]: This first question came from, again, one of our borrowers and plus subscribers and points that something most of the popular coverage on GLP1's has missed.

1:56 [SPEAKER_00]: The question is, what are your thoughts on the new British medical journal paper showing that GLP1 cardiovascular protection fades after stopping? [SPEAKER_00]: And more broadly, what is the durability of effect of GLP1's first lifestyle or no intervention? [SPEAKER_00]: So the number to keep in your head for this one is two thirds.

2:13 [SPEAKER_00]: That's how much of the weight someone regains within a year of stopping a GLP one on average. [SPEAKER_00]: All these trials point to a similar response, and let's go through them one by one relatively quickly here. [SPEAKER_00]: So we don't spend 30 minutes on this answer. [SPEAKER_00]: First is the Cermout 4 trial.

2:26 [SPEAKER_00]: So in this trial, everyone ran a course of terzepotide. [SPEAKER_00]: So that's Zepound or Monjaro. [SPEAKER_00]: By week 36, the group had lost an average of about 20% of their body weight. [SPEAKER_00]: Now at that point, the trial randomized patients into two arms that were otherwise identical.

2:41 [SPEAKER_00]: So half continued using terzepotide, the other half, switched to placebo. [SPEAKER_00]: Both arms still had the same lifestyle support and the same counseling all that entailed. [SPEAKER_00]: The only variable was the medication at this point. [SPEAKER_00]: Now, the continuation on the people still using the Terseptide, they kept losing weight.

2:55 [SPEAKER_00]: About on average, an additional five and a half percent of body weight over the next year. [SPEAKER_00]: Again, that's on top of the 20 percent or so they already lost. [SPEAKER_00]: The placebo arm regained about 14 percent of the weight they had lost previously. [SPEAKER_00]: And that again, that's over the next year.

3:10 [SPEAKER_00]: About two thirds of what the drug had produced was gone inside at 12 months. [SPEAKER_00]: Same people, same counseling, the only difference was the drug exposure. [SPEAKER_00]: That's the Cermout 4 trial. [SPEAKER_00]: The step one extension trial is a longer running version of the same type of setup.

3:25 [SPEAKER_00]: Now, some agglutide in this study, so OZampic, produced an average of 17% weight loss when people were taking the medication. [SPEAKER_00]: By week 120, the net sustained weight loss was about five and a half percent. [SPEAKER_00]: And roughly half of the previously treated group was still at or below 5 percent of their initial starting weight.

3:45 [SPEAKER_00]: Step four is another useful study in the semagletite series with similar findings. [SPEAKER_00]: Now, what you've probably seen more recently is this new headline that there are people who use these medications, use GLP ones. [SPEAKER_00]: They gain the weight back four times faster than those using lifestyle alone.

3:58 [SPEAKER_00]: This is based on a new systematic review, looking at 48 studies on the use of GLP [SPEAKER_00]: and what happens when people come off them. [SPEAKER_00]: Now, how this weight regain goes is that it's more swift earlier on, so that there's rapid regain early and slower regain later. [SPEAKER_00]: Usually plateauing around 60 weeks, the trajectories across drugs look pretty similar once the data is normalized to 2% of weight loss, though there is some difference in the amount of absolute weight regained based on the [SPEAKER_00]: Now, again, what you've seen quoted by mainstream media and my, we'll just call them GLP1 skeptics is that people regain the weight that they lost on GLP1's four times faster than lifestyle only.

4:41 [SPEAKER_00]: Now, the problem here is while that is true from a mathematical sense, the amount of weight loss. [SPEAKER_00]: from lifestyle only is way, way less than what we see on GOP ones. [SPEAKER_00]: What we see with like some agglotide and trusepotide in particular is about a three to four times greater amount of weight loss.

4:58 [SPEAKER_00]: And so if you didn't lose that much, it's going to be hard to gain that back relatively quickly. [SPEAKER_00]: So, if there's more weight to get back, the body gives it back a little more swiftly, but on a percentage of loss basis, the amount of regain is about the same, especially when we compare that to lifestyle only interventions, which I think is an interesting comparator.

5:18 [SPEAKER_00]: So, [SPEAKER_00]: We have a number of trials that I consider are probably the best lifestyle only intervention studies that we have, where they have intensive dietary counseling, intensive exercise counseling and follow-up and monitoring. [SPEAKER_00]: And so, you know, these are things like the diabetes prevention program, the look ahead, study, pounds lost, et cetera, and just to kind of go through a few of them, [SPEAKER_00]: Randomized over 3,000 adults with overweight or obesity and impaired glucose tolerance to either get metformin, placebo, or intensive lifestyle.

5:51 [SPEAKER_00]: At one year, 62% of the lifestyle group had lost at least 5% of their initial body weight, but by the 10-year follow-up, more than half of that weight was regained despite ongoing programming engagement. [SPEAKER_00]: So it's not like they stopped using GLP1, for example. [SPEAKER_00]: They continue doing the lifestyle but still gained the weight back.

6:08 [SPEAKER_00]: In the look ahead trial, there was over 5,000 adults with overweight or obesity and type 2 diabetes. [SPEAKER_00]: The intensive lifestyle group averaged about an 8.6% loss at one year compared to 0.7% without it. [SPEAKER_00]: 68% of those individuals hit the 5% weight loss threshold if we call the clinically significant weight loss.

6:29 [SPEAKER_00]: The intervention continued on for years, but by year four, fewer than half of those who achieved this clinically significant weight loss had maintained it, so they were under that sort of 5% threshold. [SPEAKER_00]: And the last one we'll cover here is the pounds loss trial. [SPEAKER_00]: This is 811 adults who were basically randomized to four different macronutrient patterns, all at a 700 calorie per day deficit.

6:49 [SPEAKER_00]: Ideas like ulcers, specific macronutrient split, [SPEAKER_00]: that people need to follow to lose weight. [SPEAKER_00]: The specific diet didn't matter, but only 15% of the participants in the pound loss, pounds loss trial lost 10% or more of their initial body weight. [SPEAKER_00]: And that's an important comparison because if you compare that to like the step one trial, where they used ozampic, smagwood tide, they hit 69% of those individuals, lost 10% or more.

7:12 [SPEAKER_00]: The surmount one trial where they used ozampic 83%. [SPEAKER_00]: hit a 10% weight loss or more, and so, you know, if you ratchet that threshold up to like 15% of their initial body weight lifestyle alone rarely hits this number, but in the step one trial, again, using some agulotod over half of them hit that threshold and using turns up a [SPEAKER_00]: I think this reframes the question here, the comparison really isn't between like, what's the durability of lifestyle only versus, uh, you know, using GLP ones and then coming off.

7:49 [SPEAKER_00]: Lifestyle alone produces a more modest, [SPEAKER_00]: loss of weight and that's being pretty charitable to it and it seems to also generate, you know, the same sort of response. [SPEAKER_00]: People regain the weight. [SPEAKER_00]: The difference is they're not stopping the lifestyle intervention.

8:05 [SPEAKER_00]: They're still doing it, but they regain the weight all the same. [SPEAKER_00]: So Austin, when you're working with somebody who's interested in starting to GLP1 or they're already on one, you answer a lot of questions regarding like coming off or tapering down or anything like that and how does that conversation go?

8:20 [SPEAKER_01]: Yeah, I have these conversations all the time. [SPEAKER_01]: It's a very common concern, common set of questions, what does long-term look like, what does maintenance look like, what can I expect? [SPEAKER_01]: And I don't tend to cite very specific data, but rather I point out that this is most often for the types of people that I'm talking with, a lifelong journey.

8:37 [SPEAKER_01]: It's often something they've been struggling with for a really long time. [SPEAKER_01]: And just intuitively, as a result, something that you've been struggling with for a really long time, be it since you were a kid in some cases. [SPEAKER_01]: it's it's kind of unrealistic to expect there's just going to be oh use this medicine for a couple weeks or a couple months and it's just going to cure this thing forever right so it's going to tend to benefit from some form of long-term treatment.

9:00 [SPEAKER_01]: It doesn't have to be the same long-term therapy indefinitely we can change it we have options we can adjust dose. [SPEAKER_01]: This whole space is evolving. [SPEAKER_01]: There might be different options for maintenance in the future, but some form of long-term treatment is more likely to be effective than doing a short course and then stopping.

9:16 [SPEAKER_01]: Just because everybody pretty much can lose weight up front as is shown pretty commonly in these trials, but relatively few can sustain that weight loss. [SPEAKER_01]: And why is that? [SPEAKER_01]: Well, the underlying biology of weight loss is pretty challenging. [SPEAKER_01]: There's an interesting series of papers, I think it's in [SPEAKER_01]: might be in the obesity medicine journal, where they title it something to the effect of like the physiology of the weight reduced state, looking at what are all the things that happen physiologically when you lose weight.

9:43 [SPEAKER_01]: In other words, what are all the ways that your body fights back? [SPEAKER_01]: And the way I frame it to patients is that the medicine does not lose the weight for you, but rather, [SPEAKER_01]: It helps you battle against your body fighting back when you successfully lose weight in the first place.

9:57 [SPEAKER_01]: So it taps down that biology of the rebound that we observe in these lifestyle studies. [SPEAKER_01]: And these lifestyle studies, these like high quality randomized intensive lifestyle interventions. [SPEAKER_01]: These are the kind of papers that I wish people would have a better understanding of when they go out on threads or Twitter and they're like, if only doctors just prescribed more lifestyle.

10:17 [SPEAKER_01]: And it's like, well, here's what happens when we try in very intensive high resource fashion. [SPEAKER_01]: People who's a bit of weight and then despite persisting in the program, the biology of the weight reduced state tends to win in the long term in the lot of these folks and yet we can.

10:32 [SPEAKER_01]: You know, arm ourselves with these tools, and we can actually win that battle way more often, and that's the way I view them as just tools. [SPEAKER_01]: So how do things tend to look long-term? [SPEAKER_01]: Yeah, most people benefit from long-term therapies. [SPEAKER_01]: Some patients are able to come down and dose a little bit in maintenance.

10:46 [SPEAKER_01]: Some patients are able to space out their dosing in maintenance of tiny fraction of people can come off the medicines entirely and maintain their their weight loss, but I don't set that as a standard expectation. [SPEAKER_01]: And so that's kind of [SPEAKER_01]: what we look for. [SPEAKER_01]: And so I also don't tend to cite very specific figures because there's just so much variation between people.

11:05 [SPEAKER_01]: So I say, here's what we see on average, this is kind of what I would generally expect, but you are going to respond as an individual. [SPEAKER_01]: And so I'm going to walk with you through this journey and we'll kind of figure it out together. [SPEAKER_01]: And that usually, you know, lands.

11:16 [SPEAKER_00]: Yeah. [SPEAKER_00]: No, no, it's true. [SPEAKER_00]: So if the average, you know, weight regained from a GLP one cessation to coming off is about two thirds of the weight that people lost will come [SPEAKER_00]: the other number that you need to keep in mind is that only about 1 in 10 people doing lifestyle only will not only achieve when a click-significant weight loss, even with a lower sort of threshold 5%, but then keep it off maintain that.

11:40 [SPEAKER_00]: Right? [SPEAKER_00]: And so that kind of speaks to your experience though, here as well. [SPEAKER_00]: You're like, look, a small fraction of folks who come off GLP ones, we have maintained it. [SPEAKER_00]: The other, you know, continued lifestyle interventions, and that's kind of what we see with lifestyle interventions generally speaking.

11:52 [SPEAKER_00]: And so yeah, we've been championing [SPEAKER_00]: Lifestyle interventions for a long time now the issue the thing now is we just have better tools to get people where we want to go and we are sort of agnostic to like how you got there provided you actually get there. [SPEAKER_01]: And it's done through generally helpful means, right?

12:10 [SPEAKER_01]: So like using a tapeworm or getting cancer is not going to be the advisable way to do that. [SPEAKER_00]: Yeah, but you need tapeworms. [SPEAKER_01]: Yeah, exactly. [SPEAKER_01]: But if you think about like the question because a lot of people reflect to like, well, how soon can I come off the medicine?

12:22 [SPEAKER_01]: You don't really tend to see very many people going and doing a consultation with a bariatric surgeon for like gastric bypass surgery or ruin why. [SPEAKER_01]: And they're like, okay, well, so how soon can you undo my surgery? [SPEAKER_00]: Right, so that's not how this works, you know?

12:34 [SPEAKER_00]: Yeah. [SPEAKER_00]: Yeah, so the question is, you know, [SPEAKER_00]: about two thirds of the way that's lost is regained within, you know, about the next year after coming off, what does that regain? [SPEAKER_00]: What effect does that have on sort of health outcomes? [SPEAKER_00]: And so this is the paper that the question asker was referring to.

12:52 [SPEAKER_00]: So in this particular paper, was recently published. [SPEAKER_00]: 37 randomized trials covering just under 10,000 adults who had been on one of these weight management or anti-BCD medications and the question that the researcher's asked was simple. [SPEAKER_00]: Once people stop the drug, what happens to the weight and the sort of cardio metabolic markers, right?

13:10 [SPEAKER_00]: And so a few caveats first. [SPEAKER_00]: Most of these trials follow people for a year or less after they stopped. [SPEAKER_00]: So the authors used some sort of statistical modeling to basically take the observed weight regain curves and the observed sort of changes in these metrics like blood pressure cholesterol, fasting blood sugar and so on, and plot those out over time.

13:31 [SPEAKER_00]: So they directly measured the rate of regain within about a year and then they kind of modeled it afterwards. [SPEAKER_00]: So across all of these anti-BC medications that were paired with a behavioral weight management program, the average regain was about 0.4 kilos per month. [SPEAKER_00]: For the newer GLP ones specifically, so some aglytide, intercepted side, the regain was actually more.

13:55 [SPEAKER_00]: 0.8 kilograms per month. [SPEAKER_00]: And so if you just read that, you'd be like, [SPEAKER_00]: These are worse. [SPEAKER_00]: They're worse. [SPEAKER_00]: Well, the thing is they just lost more weight compared to the ragly tied in some of the other older agents. [SPEAKER_00]: Same thing as the comparison to lifestyle.

14:07 [SPEAKER_00]: And I think one of the earliest characterizations that I still like and I still anchor to is that these are really just behavior changing, you know, agents. [SPEAKER_00]: rather, if you don't want to call it an anti-abesian medication, if you want to call it a behavior change agent, I like that because it all shows people to do the things they've been wanting to do the whole time, or knew that they should be doing.

14:23 [SPEAKER_00]: So anyway, they projected this forward in time and the return to sort of baseline weight where people started using these medication plans right around one and a half years for most of the [SPEAKER_00]: drugs that were included. [SPEAKER_00]: Again, these are modeled projections, not necessarily accurately measured or directly measured, because most of the studies didn't run out that far.

14:41 [SPEAKER_00]: And so they used a similar approach for health metrics. [SPEAKER_00]: So things like chemoglobin A1C, that's a measurement of how much sugar sticks to your red blood cells, over a few months, basically is your [SPEAKER_00]: blood sugar maintained within a normal range, they track fasting glucose, a track blood pressure, total cholesterol, triglycerides, etc.

15:01 [SPEAKER_00]: They all moved in the same direction. [SPEAKER_00]: Once the drug was stopped, every one of those markers started to drift back towards baseline at a relatively steady monthly rate. [SPEAKER_00]: And that kind of tracked or correlated well with the amount of weight that was regained. [SPEAKER_00]: And so we've talked at length about various benefits from taking these medications as well.

15:24 [SPEAKER_00]: We know some of the effect that we see blood pressure lowering, for example, blood lipid, lowering, blood sugar lowering has to do with weight loss. [SPEAKER_00]: But there does also appear to be some weight independent effects, particularly on things like cardiovascular disease and chronic kidney disease.

15:39 [SPEAKER_00]: We talked about the select trial, looking at cardiovascular disease and this sort of health benefit popped up early. [SPEAKER_00]: Before the weight loss even occurred, same thing in the flow trial for chronic kidney disease. [SPEAKER_00]: And so what the other thought was like, well, look, if there is some sort of weight independent effect of these medications, is that durable?

15:58 [SPEAKER_00]: Does that stick around when you stop the medication? [SPEAKER_00]: And it doesn't seem so, though, again, this wasn't tracked out for years and years and years to really know. [SPEAKER_00]: But I think, or at least the way I think about it, you can weigh in on this. [SPEAKER_00]: If you see some sort of independent effect of the medication, outside of the mechanism by which it works to achieve the observed endpoint, when you stop taking the medication, you're probably gonna stop getting that effect.

16:22 [SPEAKER_00]: Does that make sense to you? [SPEAKER_01]: Yeah, I'm racking my brain trying to think of another example of like a medicine, especially an adult medicine land. [SPEAKER_01]: If I'm thinking in other contexts like you could be like, oh, we're giving, I don't know, antinatal steroids or something for fetal lung maturity is like a one time dose and it like fixes something.

16:39 [SPEAKER_01]: But that's not something that we really tend to see. [SPEAKER_01]: And adults outside of short-term acute conditions like an infection where you take a course of antibiotics. [SPEAKER_01]: And clear the infection and then you can stop, but that's not the same as a chronic long-term condition like hypertension, hyperlipidemia, insulin resistance diabetes.

16:56 [SPEAKER_01]: So I'm having a hard time thinking of examples that where you could be like, well, why doesn't it work like that? [SPEAKER_01]: It's like, no, pretty much all these long-term conditions require ongoing exposure to the intervention to deliver a sustained benefit until we get to more of the gene therapy type stuff, which is [SPEAKER_01]: You know, not really accessible for a lot of these types of conditions.

17:16 [SPEAKER_01]: And even when it is, I suspect that a lot of the people who are a big anti-GLP one fans because the weight comes back when you stop it. [SPEAKER_01]: I don't think that they're going to be flocking to gene editing therapy either. [SPEAKER_00]: So, no, no. [SPEAKER_00]: Yeah, although they just discover a new protein.

17:28 [SPEAKER_00]: I think it's BRP or something. [SPEAKER_00]: If you read anything about that, in my system to be like at the level of the brain, very, very localized compared to GLP one receptors which are everywhere. [SPEAKER_00]: And so, you know, this is being celebrated [SPEAKER_00]: we found this new molecule.

17:41 [SPEAKER_00]: We can just attack the obesity cause and then there's some pushback where we're like, but do you get these other additional benefits that maybe you get by selecting the GOP one receptors and I guess we'll find out in 25 years. [SPEAKER_00]: Yeah, exactly. [SPEAKER_00]: So yeah, I do think the way to frame this is that the drugs work when you take them, and it's similar to kind of what we see in heart disease, where the benefit of say a lipid lowering drug like a statin, the benefit is proportional to how much they lower the lipids and how long they're lowered for.

18:12 [SPEAKER_00]: The question isn't really whether the effects persist when you're off the drug, the question is about how much cumulative risk factor reduction, the patient, you know, sort of bought during the time they were on. [SPEAKER_00]: And how do you think about it? [SPEAKER_01]: Yeah, I suppose you could think about it that way in terms of, well, we're reducing your overall exposure while you're on the medicine.

18:33 [SPEAKER_01]: Kind of, when you say it that way though, it's almost baked in. [SPEAKER_01]: It's like, okay, we'll until you come on. [SPEAKER_01]: And that's generally not the expectation that I'm setting, especially with a lot of folks who have struggled with their weight management for life long or for very, very long periods of time.

18:45 [SPEAKER_01]: You know, there's like obviously now going to be more conversation around people who may be haven't struggled with their weight for their whole life and they're looking for so called, you know, quote unquote cosmetic weight loss. [SPEAKER_01]: There was like just a question I saw in our Facebook group about this recently.

18:59 [SPEAKER_01]: And, you know, that's a separate topic, a separate conversation. [SPEAKER_01]: Those are not necessarily people where it's, you know, I would necessarily say that you're likely to benefit from needing this, from this therapy, you know, long-term or even further rest of your life. [SPEAKER_01]: Whereas there are some patients who, [SPEAKER_01]: Maybe they've undergone, you know, they've struggled with their weights since they were a child and maybe they ended up getting metabolic bariatric surgery They maybe they had some some weight loss and then maybe they unfortunately had more substantial weight regain And it's like this is a we'll call it one more resistant, you know, phenotype of obesity to intervene upon and so yeah Those are types of people were almost sometimes that expectations like

19:32 [SPEAKER_01]: You're going to do the best, being on the highest dose of this medicine, you can tolerate further rest of your life. [SPEAKER_01]: There are some people where I can say that with more confidence, and then other people who are going to more likely settle out somewhere in between, and then a smaller fraction who'll be able to use it for a bit of time, and maybe come off.

19:45 [SPEAKER_01]: But I don't set that as a default expectation for at least most of the types of patients who I'm seeing these days. [SPEAKER_01]: Yeah. [SPEAKER_01]: I do think that these conversations will evolve as these medicines become more accessible, more available, more popular, and people who maybe don't have quote unquote as resistant of an obesity phenotype might dabble in them.

20:02 [SPEAKER_01]: Then that conversation might change a little bit, but for now, based on cost and accessibility and guideline recommendations for the types of people who are getting them, yeah, most people benefit from longer term therapy for all sorts of risk reduction as well as the weight management itself.

20:13 [SPEAKER_00]: Yeah, so to wrap this up, we need to cover what these new trials don't tell us. [SPEAKER_00]: The first thing is how far does the weight regain actually go? [SPEAKER_00]: So in all of the extension trials and even the new systematic reviews that we've been discussing, the follow-up sort of ends, whether it's a year.

20:33 [SPEAKER_00]: coming off the drug and then just monitoring folks for a year or less. [SPEAKER_00]: And so what we see in the longest lasting data sets is that seems like only 75% on average. [SPEAKER_00]: That's kind of like the ceiling of the weight regain. [SPEAKER_00]: And so is there a durable effect?

20:51 [SPEAKER_00]: You know, lasting beyond that, we don't know. [SPEAKER_00]: We'll have to see five-year data, for example, to really weigh on that. [SPEAKER_00]: But we don't really know, do people gain all of the weight back? [SPEAKER_00]: The other thing we don't know is what is the body composition?

21:02 [SPEAKER_00]: of the weight regain. [SPEAKER_00]: So we've talked about this at length a few times that on these medications, on these GLP ones, the amount of lean mass loss is about the same as people see when they do a diet only sort of intervention. [SPEAKER_00]: So they don't exercise, they don't live weights, but they're using a calorie restriction through a diet only.

21:21 [SPEAKER_00]: approach. [SPEAKER_00]: And while it is overstated by mainstream media, by influencers, by again, the GLP one skeptics, we have good data showing that yeah, it is about the same as a diet only group. [SPEAKER_00]: And the risk of losing too much muscle mass or losing a bunch of strength doesn't seem to be well supported unless inappropriate use was kind of like the initial factor here.

21:40 [SPEAKER_00]: Somebody who is already frail had low levels of muscle mass. [SPEAKER_00]: probably should have been prescribed these things in the first place. [SPEAKER_00]: We just don't we just don't really see that. [SPEAKER_00]: There is some data out there like the T-rex study is going to be published at some point.

21:52 [SPEAKER_00]: It's not out there yet. [SPEAKER_00]: We've heard some pre-publication rumors milling around that look, these are people taking GLP ones. [SPEAKER_00]: They did resistance training while they were taking the GLP ones and it cut the lean mass losses in half. [SPEAKER_00]: which is what you see in these sort of when you take a diet-only group and you compare them to diet plus resistance training, they cut the lean mass loss in half.

22:12 [SPEAKER_00]: So a good signal there that there's not something uniquely sort of catabolic about the GLP ones. [SPEAKER_00]: There's also been a recent concern that with this weight loss and because there's maybe some muscle loss there too and if it is excessive it would generally cause [SPEAKER_00]: a reduction in sort of the stimulus or stress on the bone.

22:30 [SPEAKER_00]: It's a get bone loss. [SPEAKER_00]: You get osteoporosis here, although we already have data showing that. [SPEAKER_00]: Look if people lift while they're on these things does seem to preserve bone mineral density, which is exactly the same thing you see when people lose weight with diet only.

22:42 [SPEAKER_00]: I don't see the same pushback or like don't lose weight with the diet if you're not lifting weights because osteoporosis is a risk. [SPEAKER_00]: I assume somebody said that, but I don't hear it as loudly as I do with [SPEAKER_01]: Yeah, it's a very irritating, very selective sort of criticism that comes out more in social media than anywhere else in places that let you use more kind of attention, grabbing click baby headlines, you know?

23:05 [SPEAKER_01]: Yeah. [SPEAKER_00]: Yeah, the composition of regained weight was also not measured in any of these cessation trials, so we don't know is it mostly fat, is it mostly lean mass, [SPEAKER_00]: you would expect just like every other sort of intervention that causes weight loss, diet plus exercise, exercise, only whatever, when people lose weight, the first thing that gets restored is the fat mass.

23:27 [SPEAKER_00]: So it would be unsurprising to me that that's the same thing we observe with GOP ones, we just don't know, because it wasn't really measured. [SPEAKER_00]: But again, I would predict it's mostly fat mass and so this idea of like, we should lose the weight and then that gets you better set up to like bulk to gain muscle that's something we've debunked [SPEAKER_00]: So, Austin, if you have a patient, it's on a GLP1.

23:49 [SPEAKER_00]: What does the first sort of six months look like after they come off of these things? [SPEAKER_00]: Is there other specific steps that you're taking? [SPEAKER_00]: Or what are you doing here? [SPEAKER_01]: Yeah, I'm trying to provide some appropriate guidance and expectation setting up front.

24:02 [SPEAKER_01]: And I think that that experience is going to vary based on, again, how quote unquote severe or like resistant to oven obesity if you know typed, did they have at the outset. [SPEAKER_01]: So the more challenging cases, the ones where the obesity was the most severe, say class 3 obesity or beyond people who had prior bariatric surgery, people who've struggled against, since they were kids, things like that.

24:26 [SPEAKER_01]: Those are going to be the folks who have the hardest time coming off of these medicines, especially if they were using high doses to make it to achieve their weight loss in the first place. [SPEAKER_01]: People with much milder less resistant obesity phenotypes, they might have a bit of an easier time.

24:38 [SPEAKER_01]: But in general, just based on the half life of the medicine over the course of a few weeks, to say anywhere from like two to six weeks timeframe, in at varying rates, the people, the person's appetite, hunger, so-called the food noise term that you've heard, tossed around a lot of late.

24:53 [SPEAKER_01]: that that appetite will tend to come back and it comes back again to varying degrees. [SPEAKER_01]: Some a little bit more mild, some comes back with vengeance and that ends up becoming the main challenge that people have to contend with. [SPEAKER_01]: They may have to go back to, as we say, white knuckling it through the day just to try to stick to whatever plan they had in place.

25:12 [SPEAKER_01]: People with a less severe obesity phenotype who, along with the medication, established fantastic lifestyle habits, [SPEAKER_01]: strong dietary quality, strong dietary patterns, strong exercise habits, sleeping well, not, you know, using alcohol, low stress, like an optimal situation, they're going to be the most likely to either maintain or regain the least.

25:34 [SPEAKER_01]: Those who don't have either those habits in place, those who have, you know, challenges with sleep, stress, all sorts of other things that can further promote, you know, appetite increases and things like that. [SPEAKER_01]: And those who have the most resistant obesity phenotypes, those are folks who are going to have the hardest time trying to white knuckle it through the day that people who wake up and they got to go to war every day.

25:55 [SPEAKER_01]: and feel like they're doing everything they possibly can. [SPEAKER_01]: And if they, you know, I hear this a lot where they feel their perception, their experiences, oh, if I slip up once, then suddenly I gain 10 pounds. [SPEAKER_01]: And obviously it's quite a complex sort of phenomenon, but that's what the experience feels like to them.

26:11 [SPEAKER_01]: And so, you know, it's a tough situation. [SPEAKER_01]: Sometimes, you know, patients have to come off of these medicines, not through their own deliberate choice, but because of insurance coverage or costs, [SPEAKER_01]: maybe someone wants to come off in anticipation of an upcoming procedure or a surgery or because they became pregnant.

26:30 [SPEAKER_01]: And so all of these things can impact weight trajectories with varying opportunities to reinitiate therapy on the back end. [SPEAKER_00]: So yeah, yeah, I think the conversation around, you know, coming off a blood pressure medication just because you're insurance, you know, or something like that.

26:45 [SPEAKER_00]: Generally not something you have to deal with because generics are available, right? [SPEAKER_00]: Hopefully get to that point at some point because discontinuation is not really the goal here. [SPEAKER_00]: Unless there's some other reason to do so. [SPEAKER_00]: So, all right, to wrap this, GLP1 benefits accumulate during exposure to GLP1, similar to the way of blood pressure medications does.

27:04 [SPEAKER_00]: Regain after stopping on average is about 2-3rds of the weight that's lost. [SPEAKER_00]: It's regained within about a year with some of those health benefits, like the metabolic markers, including fasting blood sugar, cholesterol changes, things like that, that'll those track with the amount of weight that's regained.

27:21 [SPEAKER_00]: But coming off isn't the goal of treatment for a person stays on, and they stay on with as much of the lifestyle change exercise, healthy eating, sleeping habits, stress management that they can tolerate. [SPEAKER_00]: better. [SPEAKER_00]: If they do come off, the treatment window was the window to sort of bolster or build those habits depending on the person.

27:37 [SPEAKER_00]: So any claim about what a finite course of GLP1 exposure does for health benefits down the road is beyond what the evidence currently supports. [SPEAKER_00]: But watch the space, maybe we'll have some data on that. [SPEAKER_00]: Look, I ran GLP1s for three months and now I have a 10% risk reduction, you know, of all cause cardiovascular mortality.

27:54 [SPEAKER_00]: That'd be interesting. [SPEAKER_00]: We'll [SPEAKER_00]: All right, the next question we're talking about bones here, particularly osteopenia and heavy lifting. [SPEAKER_00]: Now, the question here was that this person's being diagnosed with osteopenia, and she knows that strength training is important for folks in her situation.

28:11 [SPEAKER_00]: But are there any guidelines I should follow around lifting? [SPEAKER_00]: Should I start more slowly? [SPEAKER_00]: Should I avoid lifting very heavy? [SPEAKER_00]: Is there an optimal way to lift, to reduce progression, to osteoporosis? [SPEAKER_00]: I think the number that frames this question [SPEAKER_00]: That's the Lumbar spine bone mineral density gain, a group of postmenopausal women produced in eight months of lifting 85% of the one-retmax or more, zero fractures in that particular study.

28:38 [SPEAKER_00]: That's the lift more study. [SPEAKER_00]: But Austin, when you think about this, think about a person with osteopenia, and maybe just clarify the difference between osteopenia and osteoporosis, and they want to start lifting weights. [SPEAKER_00]: They're like, they know it's good for them.

28:50 [SPEAKER_00]: Where does your brain go immediately? [SPEAKER_01]: Yeah, well, my medical brain first goes to thinking about, is there an identifiable cause for this osteopenia that needs to be addressed, right? [SPEAKER_01]: Because in some situations, the most common would be just a standard post-menopausal osteopenia osteoporosis relating to maybe they were unable to or didn't for whatever reason build up enough bone density early in life, and then the loss of estrogen, stimulus in the menopausal transition leads to acceleration of bone losses.

29:19 [SPEAKER_01]: And that's kind of the usual trajectory. [SPEAKER_01]: in in most cases, but there are certainly some where maybe it's osteopeenia that's premature, maybe in somebody who's actually premenopausal. [SPEAKER_01]: That raises some questions, maybe it's in somebody who has thyroid disease or parathyroid disease or chronic kidney disease or various other conditions that can accelerate bone loss.

29:37 [SPEAKER_01]: And so I want to make sure I'm not missing one of those things that needs dedicated medical treatment. [SPEAKER_01]: So I think the first step is making sure that you've had appropriate evaluation with your doctor for your osteopeenia, and it's not just being brushed off as, you know, it is what it is.

29:48 [SPEAKER_01]: The other is if you're in that kind of Perry menopausal or even the early menopausal period where you may be a candidate for some hormone therapy, that's something that may be worth discussing as well, to mitigate further progression to even, in some cases, to protect your bones as well with some therapeutic menopausal hormone therapy estrogen exposure.

30:06 [SPEAKER_01]: So there are a few things to think about from the medical side of things. [SPEAKER_01]: The next from the patient side of things that I'm thinking about is, well, how are they thinking about this condition? [SPEAKER_01]: Because that's going to heavily impact [SPEAKER_01]: You know, osteopeenia really describes a certain range of bone density changes.

30:23 [SPEAKER_01]: So if you do a dexascan and somebody gets the standard kind of T score metric, which we don't need to get into the details on here. [SPEAKER_01]: But osteopeenia's when that falls between minus one and minus two point five. [SPEAKER_01]: And then, you know, you go further. [SPEAKER_01]: into the osteoporosis range, and so it's kind of a spectrum.

30:39 [SPEAKER_01]: We set these artificial cut-offs of what defines osteopenia, what defines osteoporosis, but we have to put cut-off someplace, but it's just a spectrum of progressive loss in bone and no density, and with that progressive loss in bone or mineral density, accompanies it an increasing risk of fractures, and in particular what we call fragility fractures, or [SPEAKER_01]: fractures of bones that kind of come from traumas that would not be normally expected to cause a fracture or can even be spontaneous and in some, you know, unfortunate situations and that are that are actually pretty uncommon.

31:12 [SPEAKER_01]: And so I want to [SPEAKER_01]: get a sense of what is this person know? [SPEAKER_01]: What do they think? [SPEAKER_01]: What do they believe? [SPEAKER_01]: What are their expectations? [SPEAKER_01]: Because a lot of times, and I can sense maybe a little bit of this in the very way that this question was framed, some fear, and some apprehension about string training.

31:25 [SPEAKER_01]: Because it's kind of like when we've talked about people with osteoarthritis, and they think it's wear and tear, and we tell them, well, we got to get some exercise going, and they're like, well, isn't that more wear and tear? [SPEAKER_01]: In this situation, we see a lot of folks who think, well, my, my bones are brittle and fragile and you're telling me to load them isn't that paradoxical and it's going to cause more problems.

31:42 [SPEAKER_01]: Fortunately when it's done, you know, reasonably dosed away for the person tends to be quite safe and beneficial in, in a lot of ways, but if the person's got just. [SPEAKER_01]: severe apprehension and fear around it that I'm not going to make any progress or make an impact by just recommending that they strength train.

31:58 [SPEAKER_01]: So I want to get a sense of what's their understanding and do they have a grasp, but there is a great deal of adaptability in the skeleton. [SPEAKER_01]: Now, is it enough to return them to superhuman bone density? [SPEAKER_01]: Maybe not. [SPEAKER_01]: But I also think and this is the last thing I'll mention here, people do tend to put a lot of emphasis on the T score.

32:16 [SPEAKER_01]: on that deficit scan. [SPEAKER_01]: They look at the number, and they look at the label, and that is like the sole focus that is the defining hallmark of am I making progress or am I not making progress? [SPEAKER_01]: And I try to help people zoom out in this conversation and say, look, it is not entirely about your T score.

32:32 [SPEAKER_01]: This is not something you don't feel your T score. [SPEAKER_01]: You don't [SPEAKER_01]: feel your bone density, what you feel and what we care about is whether you experience a fracture, whether you have a more severe fracture like a hip fracture, whether you have something that lands you in the hospital because those are the types of events that have like over 50% risk of death at a year.

32:50 [SPEAKER_01]: right, those are the things you're trying to avoid and how does that happen most often from a fall. [SPEAKER_01]: So I would really like to give you the strength, the stability, the speed, the power, things like that to have good bodily control so that should you take a tumble, you are more resilient, you're more robust, you're less likely to have one of those events.

33:08 [SPEAKER_01]: where as somebody who struggles to get around at baseline and is liable to fracture a hip if they, you know, have a little bubble over the edge of a carpet in their home. [SPEAKER_01]: Yeah, those are the situations I'm much more concerned about. [SPEAKER_01]: And so I will, for example, shout out my, my mother in this situation, who has had a osteopenia for many, many, many years, and I have coached her, gotten her to string train.

33:28 [SPEAKER_01]: I think she weighs probably around 110 pounds, I think she can deadlift around 145 pounds for a set of three, maybe a set of five, something like that. [SPEAKER_01]: And then, you know, last year we were playing some pickle ball and she actually took a tumble on the court. [SPEAKER_01]: She fell.

33:43 [SPEAKER_01]: And obviously, the first place my mind went was, oh no, you know, I know she's got asked the opinion. [SPEAKER_01]: She just took a fall. [SPEAKER_01]: I got to quickly just make make sure, you know, because she's at some degree of written and she's completely fine as a result of that. [SPEAKER_01]: And that's just obviously an anecdote.

33:57 [SPEAKER_01]: I don't want to over-generalize that to that to everyone. [SPEAKER_01]: But that was the first and only time I've ever seen it. [SPEAKER_01]: And it was in like a high power speed, dynamic ballistic type activity. [SPEAKER_01]: And she actually tolerated just fine, despite having that bone density.

34:08 [SPEAKER_01]: So, [SPEAKER_01]: The robustness, the resilience of the person, their ability to get around and interact with their environment and do their activities and things like that. [SPEAKER_01]: That's what I'm really trying to promote along with this message of adaptability in people. [SPEAKER_01]: So, I, to directly answer this person's questions, they don't necessarily need to start quote more slowly than somebody in their same situation who is matched, but does not have osteopenia.

34:31 [SPEAKER_01]: In other words, I would still start them out similarly with their strength training. [SPEAKER_01]: should they avoid lifting quote very heavy, not any more than I would advise somebody else who doesn't have osteopeenie in their same situation, avoid lifting something that they are not prepared to lift.

34:44 [SPEAKER_01]: And there is not an optimal way to lift to reduce progression outside of it should be sufficiently dosed and matched to their. [SPEAKER_01]: current level of fitness. [SPEAKER_01]: And again, those are parameters that I'd recommend regardless of whether the person's T score is plus one or if it's zero or if it's minus 0.5 or if it's minus minus minus one across that spectrum.

35:04 [SPEAKER_01]: Get a sense of what they can do. [SPEAKER_01]: Taylor, you know, the initial starting intervention and progress it in line with their adaptation as they go. [SPEAKER_01]: The T score itself does not make me say, oh, well, in this situation, I suddenly need to do a radically different training [SPEAKER_00]: Yeah, I think starting from a place of understanding that the bone is adaptable, just like much of the rest of our organism, if not the rest of our organism is fundamental for kind of moving forward.

35:28 [SPEAKER_00]: And so just to kind of hammer that home, I do want to recapitulate some of the specifics of the lift more trial because if there was a randomized control trial on this particular question, asker, this would be it. [SPEAKER_00]: It's 101 postmenopausal women, the mean age was 65, their T scores were all below.

35:45 [SPEAKER_00]: 1.0 so frankly, osteopeenic. [SPEAKER_00]: They were doing high intensity resistance training and they also call it impact training. [SPEAKER_00]: We'll get to the specifics of that here in a second. [SPEAKER_00]: So twice per week, for 30 minutes, they were doing deadlifts, backsquads, overhead press, five sets of five, above 85% of their one rep max.

36:01 [SPEAKER_00]: They did jumping chin-ups and they landed, they jumped down with straight legs. [SPEAKER_00]: That was the impact sort of training here. [SPEAKER_00]: All of that stuff provides a certain amount of load on the bones, a certain amount of mechanical strain, which is important to get the bones to actually remodel.

36:15 [SPEAKER_00]: And they saw great results in bone mineral density. [SPEAKER_00]: All of their functional measures improved. [SPEAKER_00]: And as far as a safety signal here, there was only one minor backspasm, two missed sessions, no fractures. [SPEAKER_00]: very, very safe. [SPEAKER_00]: This is also replicated in men, the lift more M trial, which I thought was interesting, but there does seem to be this dose response relationship between the amount of weight that people are lifting, relative to their maximum and the change in bone mineral density.

36:39 [SPEAKER_00]: And so you can go into the research and find meta-analyses that show in, not so great results from exercise, because most of those are underdosed. [SPEAKER_00]: It's light resistance training, water-based [SPEAKER_00]: It's just not enough mechanical strain on the bones to get in to do the thing that you want.

37:00 [SPEAKER_00]: That being said, all exercise improves the sort of functional scores of people. [SPEAKER_00]: And so the way I think about this is that exercise works two ways. [SPEAKER_00]: One, it makes you less liable to fall. [SPEAKER_00]: because improves your function, right, balance, things like that, spatial awareness scope, so on and so forth, strength, just generally speaking.

37:17 [SPEAKER_00]: And if done correctly, dose correctly, can increase your bone mineral density. [SPEAKER_00]: So you get, you know, this sort of double hit of gains, if you will. [SPEAKER_00]: So to bring it home, I think osteopenia, this position, this place of the person's in, that is the time to act, not to back off or take it easy.

37:34 [SPEAKER_00]: With more trial, then again, these are people that are further down, the pipeline, than you on average, generally speaking, [SPEAKER_00]: Apparently tolerated that very, very well, very, very safely, and it did lead to an improvement in their bone mineral density in addition to things like strength and, you know, you would expect improvements in strength and improvements in general function to all sort of false to get, again, two different types of gains here.

37:58 [SPEAKER_00]: All right, that is 10 questions. [SPEAKER_00]: We appreciate every one of them, Austin, great job before we close a few quick notes. [SPEAKER_00]: For anyone on a GLP one who is navigating in osteopenia or moving through parry menopause, our coaches and template library are great resources, and you get discount from both just by being a barbell medicine plus subscriber.

38:15 [SPEAKER_00]: Next month's direct line. [SPEAKER_00]: That is now open for questions on your dashboards, so head over there and hit us with your best shot. [SPEAKER_00]: I'm Dr. Jordan Fagan Mom, that's Dr. Austin Baroque, this has been The Direct Line for Barrel Medicine in April, 2026, we'll catch you on the next podcast.