AMA #26: Continuous glucose monitors, zone 2 training, and a framework for interventions

**Peter Attia** (0:11)
Hey, everyone, welcome to a sneak peek, Ask Me Anything or AMA episode of the Drive podcast. I'm your host, Peter Attia. 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 peterattiamd.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 episode 26 I'm once again joined by Bob Kaplan. In today's episode, we field a bunch of questions that are kind of follow-up questions to topics we've recently done deep dives into.
The two main themes are more follow-up on CGM and more follow-up on zone two. Now, when Bob first told me that those were going to be two of the things we're going to talk about, my first thought was we have nothing else to say on these topics. We have spent so much time on them. But it turned out I was wrong. There were a lot of really good questions here and things I hadn't considered. So if you find yourself wanting on either of those topics, this episode is definitely for you. If you think you know everything on those, it's probably still for you. The time of the recording here was in the middle of the tour de France, so we had a little digression on performance physiology and cycling.
Now remember, if you're a subscriber and you want to watch the full video of the podcast, you can find it on the show notes page. If you're not a subscriber, you can watch a sneak peek of this video on our YouTube page. So without further delay, I hope you'll enjoy AMA 26

**Bob Kaplan** (1:49)
Hello, Peter.

**Peter Attia** (1:52)
Hey, Bob. How are you, man?

**Bob Kaplan** (1:55)
I'm doing well. How are you?

**Peter Attia** (1:56)
I'm great.

**Bob Kaplan** (1:58)
You ready for an AMA?

**Peter Attia** (1:59)
I am.
I saw the agenda. It's very aggressive.

**Bob Kaplan** (2:04)
That's how I like it.

**Peter Attia** (2:05)
Ambitious.

**Bob Kaplan** (2:06)
Yes.
To say the least. I don't know if we'll get through everything, but we did get a lot of follow up questions on CGM based on our previous, actually, I think it was the previous AMA where we talked about glucose. We talked about mean glucose, glucose variability and glucose spikes. And then we also had that Sunday email on CGM and non-diabetics. It was related to a JAMA perspective talking about it. So there's a bunch of questions on that.
We also have a couple of questions on Aura, the sleep wearable, the Aura ring. We've got some exercise related questions and we may work in one or two additional questions if we have time. How's that sound?

**Peter Attia** (2:51)
I think it sounds like a good list.

**Bob Kaplan** (2:53)
Okay.
So Peter, since we have a lot of these CGM related questions, one of the things that I've heard you talk about is you have a framework for interventions that I think will be really helpful in laying the foundation for how you think about CGM and their use in different populations. So can you start off by telling us a little bit about that framework?

**Peter Attia** (3:14)
Yeah, so again, it doesn't pertain to CGM specifically. It pertains to anything that comes across my plate.
And the first time I actually contemplated this was really when I started trying to look critically at the data around meditation. So this was probably about maybe eight to 10 years ago. But anyway, it basically asks a series of questions. So the first question is, what is the risk of harm from doing this thing? That's a direct question. So if you do X, how high is the probability of harm?
The second question is obviously the contrapositive of that. If you do X, what is the probability of benefit?
And then the third question, and by the way, before I go to the third question, those first two questions are so obvious that they're almost not worth stating. And of course, that's mirrored in the way the FDA organizes drug trials, right? So a drug trial is organized first by, well, after you get through the preclinical data, the animal work, after the IND has been filed, your first trial in humans, which is called a phase one trial, is looking at harm. I mean, it's typically a small trial with dose escalation that is only trying to understand if, as you escalate the dose, do you see an increase in side effects.
Very occasionally, you see some benefits in a phase one trial. And if you do, that's interesting, but you generally can't take it to the bank because the study is so small and generally it's quite homogeneous. So that's when you move on to phase two studies, which are geared towards efficacy, i.e. is this thing doing good? And of course, if the phase two trial is positive, you move to a much larger trial called a phase three trial, which really doubles down on efficacy. Of course, both of these trials will continue to be able to pick up any signal of harm. So you're always in the spirit of trying to capture that. But the real point here is you're raising the bar, so to speak, for what you're demanding of this. So again, what's the risk of harm? What's the probability of benefit? Are two obvious questions. I think the third question then is, what's the opportunity cost of this intervention? And I feel like I've talked about this on a previous podcast before, and maybe it was even one of ours, but there was this device, sort of a device that you would listen to and it would supposedly put you in a trance. And the company that was proposing this thing had all sorts of theoretical benefits from using it. If you listen to this device, you are less likely to get breast cancer and all of these other things. So was there any harm in this device? As far as I could tell, no. I really didn't think that listening to this device was harmful in any way. Was there any benefit of this device?