Episode #391: VO2 Max vs. Cardiorespiratory Fitness, GLP-1 Costs, and the 10,000-Step Myth | Direct Line March 2026 (Free)

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0:30Jordan Feigenbaum:Hi, this is Alex Kantrowicz. I'm the host of Big Technology Podcast, a longtime reporter and an on-air contributor to CNBC. And if you're like me, you're trying to figure out how artificial intelligence is changing the business world and our lives. So each week on Big Technology, I bring on key actors from companies building AI tech and outsiders trying to influence it, asking where this is all going. They come from places like NVIDIA, Microsoft, Amazon and plenty more. So if you want to be smart with your wallet, your career choices, in meetings with your colleagues and at dinner parties, listen to Big Technology Podcast wherever you get your podcasts.

1:19Jordan Feigenbaum:welcome back to the barbell medicine direct line our monthly ask us anything for our barbell medicine plus subscribers i'm dr jordan feigenbaum we've got a stacked set of questions today and a lot of it comes down to one recurring theme the advice that was supposed to protect you might be doing the opposite. And to help me unpack all of this, we have the second most handsome doctor in North America. Dr. Austin Baraki, what's going on, dude?

1:40Austin Baraki:Hey, doing all right. I'm looking forward to the breadth of topics that you've pulled together or that our audience has pulled together. I just wrapped up some training this morning and I'm comfortable, ready to go.

1:50Jordan Feigenbaum:All right, let's get into the first question. This one's on VO2 max versus cardiorespiratory fitness for longevity. The question is, is VO2 max the metric we should or could reference for cardiorespiratory fitness when it comes to longevity? Dr. Eric Topol points out the data comes mostly from measures of cardiorespiratory fitness, not actual measures of VO2 max. How does this square with Dr. Peter Atiyah's recommendations for VO2 max? So to start, yeah, these aren't the same things. VO2 max and cardiorespiratory fitness are distinctly different. And most of the longevity studies that Dr. Atiyah has cited, they don't actually ever measure VO2 max.

2:26Jordan Feigenbaum:We can fully concede that. VO2 max, for those who are listening at home and may be unfamiliar with what it actually is. It's a measurement of your maximum oxygen uptake. It usually requires a maximal effort test with a metabolic cart to get a real number. Cardiorespiratory fitness, on the other hand, is more broad than that. In most large studies, it's an estimated treadmill test, estimated exercise test sort of thing. You take it to tolerance where people either have signs if it's like a cardiac rehab sort of situation or just otherwise they feel some breathlessness they can't continue. And so it's a, you get a measurement of metabolic equivalence at peak effort.

3:02Jordan Feigenbaum:You can also get a submaximal test. There's also questionnaires. There's a bunch of different ways to test it, but most of the time in the research, it's a exercise tolerance test sort of thing. So Atiyah, despite this gives specific VO2 max percentile targets by age and sex in his book, despite the underlying studies, not actually measuring that. So he says, despite all of this, that VO2 max is the single most powerful marker for longevity. He's been saying it on his podcast, it's all over his book Outlive. And honestly, he's probably right directionally, but Dr. Topol and some other people on Twitter have recently been kind of like taken the task for this.

3:41Jordan Feigenbaum:And particularly Dr. Topol's pointed critique suggests there's like a meaningful scientific problem with that claim. Austin, you want to walk us through that claim?

3:50Austin Baraki:I can do my best. This is an area where, you know, although the conversation is interesting, I see part of the issue being that folks like Dr. Atiyah, quote unquote, optimizers are very interested in discrete and concrete metrics that they can aim to optimize. And there's, I forget the eponymous law that once the measure becomes the outcome, it often like ceases to become a good measure, right? And so you're right that directionally, this is accurate in the sense of VO2 max as a type of assessment for cardiorespiratory or aerobic fitness, but it is incomplete. And so why aiming to just specifically target that outcome with your, you know, your training protocols, just aiming at VO2 max optimization might be missing some things.

4:43Austin Baraki:And so some of the commonly cited studies in this realm, one in 2022 in JAMA Network, open very frequently cited that looked at exercise capacity assessed by the METS kind of measurement that we've talked about before from a stress test, not a direct VO2 max measure, but rather the MET performance is then mapped onto your VO2 max kind of percentiles. And there are several others that also use, you know, performance-based metrics, like another one in JAMA from 1989 that used a treadmill time. That's a performance-based test. Dr. Topol's point and many others who have made similar arguments is that we're kind of conflating or looking at various measures of cardiorespiratory fitness, which is a much more broad and kind of like an umbrella description of what we're talking about, and trying to collapse it down into this single metric of VO2 max, which is a very particular thing that has very particular limiters, meaning that there are certain things that it will tell you more about.

5:46Austin Baraki:So it might tell you a little bit more about like cardiac function, for example, like central kind of adaptations and a little bit less about some of the more peripheral determinants of cardiorespiratory like performance. And so, you know, the relationship between between cardiorespiratory fitness and longevity is pretty clear. No one is really arguing that or debating it at this point, at least I hope not. I think maybe some of our former colleagues still maybe underprioritize this in the strength training space, but people who are reasonable generally agree that being more fit from a cardiorespiratory standpoint is going to be both associated with and to some extent causally related to improvements in health and longevity and lifespan and healthspan and all of these good things that we're looking after, but rather that collapsing it down into just VO2 max is short-sighted, given that most of the evidence that we're drawing this off of looks at actual performance.

6:39Austin Baraki:And so what kind of things can you draw from this? It might be like, hey, maybe why don't we just pay attention to performance and we don't need to use this very particular metric. People who are very much into biomarkers and biohacking and optimizing very specific numbers on a lab test or something that they can, you know, go out and do or calculate, might not love that. They might get a little uncomfortable with it. But at the same time, I don't know that you or I would have a problem with like picking a benchmark test and aiming to improve that over time and saying if that performance test, that road test that is relatively standardized over time is generally improving, then it is a reasonable take to say my cardiorespiratory fitness from central adaptations to peripheral adaptations to VO2 max all of that is improving likely improving a variety of other health outcomes and longevity as well i don't know what are your what's your take there yeah i don't want to be like an atia

7:30Jordan Feigenbaum:apologist you know in some ways and reframe his actual um discussion or his claims because honestly i'm not super familiar with everything he's ever said about this it is totally possible that he's overstated on this perhaps even even likely but i think the pushback is mostly around Look, he gives these specific percentiles that people should be targeting. And like, that's the benchmark. And I can understand some criticism around that if they're not really based on the metric that he's telling people to chase. But that seems fine. But it seems more of like a semantic sort of thing to me, because I actually think it's useful to have a target like this.

8:08Jordan Feigenbaum:The analogous would be like a strength, you know, a strength standard, like you should get your strength up to this much on a particular exercise or this particular test. and it's like, yeah, well, not all encompassing. It does give us what I view as a very important variable with respect to exercise prescription. It's the monitoring thing because exercise works better when it actually works to make you fitter. So it's not just like do the guidelines, double the guidelines. It's like, yeah, but do it in a way that makes you stronger, that improves your cardiorespiratory fitness. And the VO2 max is a reasonable sort of test of your cardiorespiratory fitness.

8:43Jordan Feigenbaum:There are other ways to test it too. so he could have picked you know a 20 minute cycle time trial test and say look here are the here's the data we have on that or like a would or a power output sort of thing you could have done any of that we we put in our barbell medicine vital five like look vo2 max here are some targets to get people to shoot for mainly because it's not enough in my opinion or our opinion to say yeah just exercise do it in a way that's productive and also by the way the exercise tolerance test has a really good correlation to actual measured vo2 max so it's not like their worlds apart.

9:15Jordan Feigenbaum:Anyway, there's just more stuff or different things that are being captured in that test. So I don't think a TIA is wrong per se. It may be wrong about the precision, but right about the direction. Um, it's not really the same error. And I do think, again, as you mentioned, nobody's arguing against like cardiorespiratory fitness being useful. I just think, sure. If you want to say the specific percentile thresholds are not exactly as evidence-based as he's leading on fine. You could just, you know, chastise him for not being a great science communicator in this particular respect. Although, what's the harm?

9:46Austin Baraki:Well, think about it this way. Here's the pushback to your pushback on this, which we're kind of doing in real time here. You know, if we're in agreement that cardiorespiratory fitness is the real thing that we care about, but we want a metric and we use VO2 max, then what happens, and this is what we observed in that space a fair amount of the time, is people looking for very specific, quote-unquote, protocols aimed at optimizing that one measure, right? To the potential exclusion or kind of deprioritization of other possible ways of training that would also improve cardiorespiratory fitness in other ways, even if not kind of quote unquote optimized towards VO2 max.

10:25Austin Baraki:So this is where you'll hear them talk about this particular interval training protocol that was done in the study and was shown to improve VO2 max. And I would do that instead of, you know, this other form of aerobic training or cardiorespiratory training. An analog that I might be able to draw here is like, let's say that we look at the strength training evidence. And it's like, yeah, strength, pretty clear, you know, predictive power, good correlation with health outcomes and things like that. And so the metric or the outcome that I'm going to use is grip strength. And so then all of my training protocols are going to be oriented around improving my grip strength.

10:57Austin Baraki:Is that going to make you healthier compared with not doing any strength training? Sure. Are there a lot of other ways that you could train to improve your strength that would also be useful, even if you were not singularly focused on that one potential metric. Absolutely, right? You could pick any exercise. Maybe somebody else might say, oh, it's your, you know, 5RM back squat. It's like, okay, well then the only way that I'm gonna aim to improve my strength for health and longevity is by back squatting and everything's in the order. It's like, yeah, there's a lot of ways that you could train for strength that will improve your health outcomes and some that might even be worth including that you are deprioritizing because you're very focused on this one measure.

11:34Austin Baraki:So I think that's kind of like where there's a little bit of daylight between these different positions, these different takes. Having metrics is great, but collapsing everything down into that one metric and making that the primary outcome of interest to potentially the exclusion of other valuable aspects might be where some people could improve the way they go about this. Yeah.

11:57Jordan Feigenbaum:Just to wrap this up, you'll note in the Barbell Medicine Vital 5, it wasn't just a VO2 max number. It was also some field tests that could be done across different modalities. And we kind of explicitly recommend that. So we don't hamstring people by saying, you just got to get your VO2 max up and do anything else that doesn't directly raise your VO2 max is useless. We're just like, look, we want to improve your cardiorespiratory fitness. Here are various benchmarks you can chase or monitor your progress over time, because I think it does add a critical element that's missing from the current guidelines, which is not do the exercise, but also make sure it works for you.

12:32Cool.

12:33Jordan Feigenbaum:Next question, more on GLP-1s. Will this ever be sufficiently handled? No, absolutely not. There will be no more GLP-1 questions. So the question is that GLP-1 medications like Ozampic, Wegovy, Manjaro, Zepbound, they can be transformative for a lot of patients, but they're also very expensive, sometimes over$1 ,000 a month without insurance. Is there any real evidence that that's going to change, that prices are going to come down? And I want to be honest about the timeline here. So the bottom line, without pretty strong insurance coverage, long term use is difficult to access for many folks unless they're willing to pay out of pocket.

13:10Jordan Feigenbaum:The question is, are generics coming soon? And, you know, loraglutide became a generic, although there was some evergreening type situation that was going on with the manufacturer. But I think the main thing here with respect to generics is that GLP-1s are either peptides or biologics. You know, this is kind of arbitrary line in the sand based on their structure, peptides officially by the FDA being like 40 amino acids long or less. And then if it's above that, it's a protein drug or a biologic. So because of this structure, they are more challenging to make. And there are many different ways that manufacturers can maintain their patent on them, you know.

13:50Jordan Feigenbaum:So not just the formulation, but the pen, for example, and then other aspects of the drug. so they can like kind of maintain or limit generic development. Some thought that biosimilars could be a competing product. These are like highly similar to an approved reference protein drug or biologic. Humira, there was some development here. And there are some biosimilars being developed in China and a few other countries, but none in the U.S. right now. So to me, I don't think there's any generic Ozempic or Zep bound coming soon, mainly because the key patents don't really expire until the 2030s. And even then, you've got to have a manufacturer who's willing to make these things and the pen, which I think requires a lot of funding.

14:35Jordan Feigenbaum:What do you think about that?

14:38Austin Baraki:Yeah, just a few kind of, I guess, things from doing this day-to-day with patients is that while the list prices are certainly exorbitantly high in those ranges that you described, at this point in time in 2026, nobody is paying that amount in the US or should be. And that is because of the manufacturer's direct access programs. So with Eli Lilly, they have Lilly Direct, which I have no affiliation with, to be clear. And Novo also has their own NovoCare kind of direct to manufacturer option. And so if you are somebody who for some reason, you know, maybe either with insurance or without it is still paying that amount, you should talk to your prescriber.

15:18Austin Baraki:So Eli Lilly through Lilly Direct, Terzepatide or Zepbound is available in the range of$299 to$449 a month. Wigovi through NovoCare, depending on the oral or the injection formulation, ranging from$149 to$349 a month. And so these prices most recently dropped last fall, I believe, might've been sometime around October. Prior to that, yes, you know, even people who wanted to go cash pay we're paying these much higher and more exorbitant prices. So prices are actively coming down. These companies are competing against one another. There's a lot of movement between the two companies, other potential entrants into the space, other non-GLP1-based therapies, so like amylin analogs and things like that.

16:03So ultimately what I'm seeing is drugs that are increasingly effective,

16:08Austin Baraki:increasingly safe increasingly like long acting so loraglutide was once a day and then these more recent ones are once a week there was one recently that was studied that's once a month and things like that so more effective safer better tolerated longer acting and because all these players are competing with one another yes the prices are gradually coming down as i mentioned the current cash prices that people are able to get range from like say 150 to 450 in general direct from the manufacturer, at least in the US. And I have a substantial portion of patients who are using those options when their insurance is not covering it for whatever reason.

16:43Austin Baraki:But yes, I do expect that cost will continue to come down. That is definitively what I expect to happen. It might take longer than all of us would like, as it already has, but that is what I expect to happen. As far as generics, yeah, that's a complicated question because these aren't just one drug. They all have some unique considerations to your point. The idea of a generic manufacturer producing an auto injector in pen form, like that's a there's not too many examples of that that I can think of off the top of my head. Whereas the oral options, as those become generic, those are far more likely to become available in generic form once those patents expire, although there is still the caveat of like the complexity of the manufacturing.

17:25Austin Baraki:So with oral semaglutide, for example, that is a peptide and the, you know, pretty advanced pharmaco engineering was needed to make that orally bioavailable. The newer Lily oral product that we're expecting is going to be approved and available this year is called Orforglypron. And that is actually a small molecule GLP-1. So that is not a peptide in the same way as the injectable GLP-1s or oral Wagovi. And therefore, it doesn't necessarily require that same degree of advanced bioengineering. So to the extent that we're able to get oral small molecules, that would be like a kind of a grail to work towards and would be something that would make these much more easily accessible.

18:05Austin Baraki:So yeah, if I fast forward a year, does the space look like radically different? You know, it's evolving actually pretty quickly, but not, you know, on that rapid of a timeline. Do I expect like the whole space is going to be overhauled? But if I look maybe, you know, three, four, five years, it's going to be wild because if I rewind five years, you know that was even pre pre zep bound pre terzepatide era all we had was ozempic and wegovi was just kind of coming on the scene fast forward 10 years who knows what this space is going to look like so a lot of evolution a lot more options ultimately like all good things i think for people are coming more options more effective safer better tolerated cheaper that's what you know for for whatever you think about capitalism that is what it is doing for us in this space so reasons for optimism, at least on this front for people, I think, in the future.

18:52Austin Baraki:Yeah.

18:52Jordan Feigenbaum:Yeah. The honest answer for patients right now is that the market pressures do seem to be working in their favor, whether it's due to compounding pharmacies continuing to sell these things that maybe shouldn't be happening. And subsequently, there's now direct consumer programs from the manufacturers themselves. So these assistance programs, you should ask your doctor about that if you currently are paying, you know, four figures a month for these sort of things. And then, yeah, I suspect with continued R &D, we're going to have better agents available. Again, comparing liraglutide, you know, once a day, not terribly effective to orfolglipron or even, you know, retatratide.

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