Peter Attia· MD
am i correct in saying we don't to date and tame we will talk about in a moment but we don't to date have any clean example of a study that demonstrate uh metformin's giro protection look you're right in humans you can say it on many studies but it's certainly true with diabetes diabetes is a problem because it's a progressive disease no matter what and and you can go and go back to the data and show whether the people who are metformin from the beginning versus other have done better and whether it stops and there there's a lot of of of things but first of all you're right you're also right about we had this discussion about the mortality data and you pointed out that maybe the control were not controlled enough for getting them out for some reason you watch them all the time you're absolutely right even even the clinical studies are not perfect studies but there are still enough of clinical studies or small studies that gives you the confidence so for example there are two studies on people with mild cognitive impairment that were treated with metformin one for half a year and one for one year and some of the outcomes have changed and there is no different in how they were treated um you know in other words they didn't have diabetes so it's not that they switched to other medication so there there are lots of examples like that but you're right if if this was compelling if this was compelling on its own um you could argue we wouldn't have to have tame even right um and really tame is not about it's not that we they were not studies for each one of the diseases but there was no studies to be agnostic of the diseases okay we we don't care look we're targeting aging we don't care what disease you have and we don't care which disease you're going to take to get if you're obese and your mother's diabetes you're going to get diabetic necks we have to thinks in general science that aging is going to drive your next disease yeah and therefore it's the cluster that is going to to count and we're counting the clusters by the way we had this discussion about mortality uh mortality you get a point for mortality just like you get a point for a disease and the important thing of the cluster is that we cannot do time study imagine we do a time study and in two years cardiovascular disease comes up as as significant and there's an insignificant reduction of cardiovascular mortality and the fda will say hey we have to stop the study because we cannot go with the study when with placebo right and it will ruin it for us so the whole the whole problem of the statistics obtain is to make sure that we're not getting to any significant in any disease just to trends and that the only way to stop by the way the one one way to stop the study is if mortality is significant that will trigger a stoppage of this study otherwise what will stop the study is the integral approach of right so statistically you just can't your biggest mistake here is overpowering the study for mortality and therefore appropriately powering the study for subs subsets of mortality yes is that is that a safe assessment substance of mortality you mean diseases disease specific mortality is what i mean yes well let's talk a little bit about tame this is something you and i spoke about god two years ago um so this is a study that is going to look at people who do not have type 2 diabetes right it's an exclusion criteria and they are over the age of 65 65 to 79. okay so 65 to 79 no diabetes no type 2 diabetes any other exclusion criteria yes but it's not important for our discussion so if you have cancer in the last year okay things like that yeah very specific if you had a heart attack in the last three months but again these people are going to be taking statins they're going to be taking medication for blood pressure some of them will be overweight some of them will be normal weight presumably right the point the point here though is that look we don't want to recruit a bunch of centenarians together you know you don't want to be you don't recruit future centenarians you're not going to get an answer so they have to have something okay they have to have for example walking speed less than six uh meter you know per second is is a an inclusion criteria you have to have something i see so you don't want you don't want exceptionally fit people in this group right you know it's almost like you want to take the patient population that predimed started with because this was a primary prevention study for cardiovascular disease that found a statistical significant difference in under five years i think it was four and a half years they expected to go for seven um so so it's you're really looking for that type of population you you you really do want people who are gonna i mean it's morbid to say this but you're looking for people whose risk of death in the next five years is is high enough that you're going to move the needle now the the risk of that is you get a negative study which means there is no difference in all-cause mortality or even disease specific mortality and the counter argument might be you started too late you know that's like applying the brakes on a car that's driving towards a cliff when it's only 20 feet from the cliff should this be a lot longer study where you start this at people when they're 50 and your ex your five-year mortality expectation is very low again i'm not saying this can be done because that's a very expensive study but it is a risk here correct there are two arguments here uh you know first of all we needed to do look to st to start a study at 50 where you have to show mortality is a 20-year study we we we cannot afford it