The impression I got from asking people like James about metformin side-effects when I was trying a cost-benefit is that most of it has quick onset, like the gastrointestinal distress, and if you can’t fix it by modifying the dose, you can simply discontinue it ie you have option value. This would reduce the EV a little but is not that big a deal. After all, metformin is one of the most (the most?) widely used chronic prescription drugs in the world & regarded as very safe, so the side effects can’t be that bad, one would think.
The question of redundancy with other interventions is a more concerning one. Not all the metformin papers are positive in this regard. Here’s a small paper suggesting that metformin blunts the benefits of exercise, and “Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug”, Wu et al 2017, suggests part of metformin’s benefits is by changing the microbiome, but of course, exercise or diet or lifestyle changes might also be changing the microbiome in precisely the same way… For diabetics, who have done what little they are able or willing to do, that presumably is not happening enough to cure their diabetes and so the average metformin effect is still worthwhile, but for those more rigorous about longevity, who knows?
I have similar concerns about baby aspirin and everything postulated to involve inflammation, and perhaps also the senolytics as well: they often seem to be hypothesized to be acting through similar pathways (eg inflammation causes/is caused by senescent cells, some say, but if exercise kills senescent cells by inducing autophagy, doesn’t that imply it’d be at least partially redundant with taking a senolytic drug?). I’m not sure what could be done here except to directly test the potential for interactions in factorial experiments.
The impression I got from asking people like James about metformin side-effects when I was trying a cost-benefit is that most of it has quick onset, like the gastrointestinal distress, and if you can’t fix it by modifying the dose, you can simply discontinue it ie you have option value. This would reduce the EV a little but is not that big a deal. After all, metformin is one of the most (the most?) widely used chronic prescription drugs in the world & regarded as very safe, so the side effects can’t be that bad, one would think.
The question of redundancy with other interventions is a more concerning one. Not all the metformin papers are positive in this regard. Here’s a small paper suggesting that metformin blunts the benefits of exercise, and “Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug”, Wu et al 2017, suggests part of metformin’s benefits is by changing the microbiome, but of course, exercise or diet or lifestyle changes might also be changing the microbiome in precisely the same way… For diabetics, who have done what little they are able or willing to do, that presumably is not happening enough to cure their diabetes and so the average metformin effect is still worthwhile, but for those more rigorous about longevity, who knows?
I have similar concerns about baby aspirin and everything postulated to involve inflammation, and perhaps also the senolytics as well: they often seem to be hypothesized to be acting through similar pathways (eg inflammation causes/is caused by senescent cells, some say, but if exercise kills senescent cells by inducing autophagy, doesn’t that imply it’d be at least partially redundant with taking a senolytic drug?). I’m not sure what could be done here except to directly test the potential for interactions in factorial experiments.