Great comment. I agree that it is always a trade off. But if we can do some simple things to live independently without any debilitating disease until we die, it may be worth it
In my opinion, we here look at end of life / death like a battle instead of considering it to be a natural phenomenon.. and in the process we may focus way too much to win this un-winnable battle .. and in fact, it is not a battle at all .. and in the process of this focus, we may involuntarily focus on quantity and may ignore the focus on quality .. just my opinion.
Good one Ram and the last sentence is spot on! As someone who has spent nearly 30 years in traditional drug discovery and development, I find it hard to envision a 'magic pill' for longevity that can get the job done with a reasonable risk/benefit ratio - at least within our current capabilities.
Also, even if one were to demonstrate the above in say a small Phase 2a/b trial, there may be regulatory hurdles since as of today, FDA does not recognize aging as an 'indication' so one wonders how to go about designing a pivotal trial. Of course, above applies for only new chemical or biological entities i.e., no prior FDA approval for any other indication.
Having said this, I think there may be opportunities in future for a narrow range/applications say specifically for cardiometabolic or immune function or musculoskeletal etc. Of course, they too would have to be rigorously tested before we have the confidence for routine clinical use.
To underscore the last comment, a recent paper on both benefits and risks for calorie restriction makes the point quite well as in a future longevity drug may face the same in terms of trade offs IMO.
Thank you for your in-depth look at the business of selling hope. I've linked to your article in an update of my tongue-in-cheek post about mythical "Life Extension Pills."
Thank you Dr. Skolnick. Dr. William Bestermann has been a strong advocate of metformin for diabetes and metabolic dysfunction, and is probably the only true viable candidate for longevity. Hope we get some early results from the TAME trial. I have always wondered if metformin is safe for pre-diabetes and people who are iffy in their blood sugar and whether it would work well for them (since I am one of those people).
BTW, When my HbA1c passed the upper limit of normal for the first time, I asked my PCP if he would prescribe metformin, and he agreed to without any hesitation. I’ve been taking the 500 mg XR tablets bid pc with no ill effects, and had a decisive lowering of my HbA1c. I’m anticipating all the other metabolic health benefits Dr. Bestermann describes in detail.
Really useful Dr. Skolnick. When my Hb1Ac passed normal a while back but now it is lower than the guideline ( just barely). I am thinking of requesting my PCP for a prescription.
What convinced me, and my PCP, that my HbA1c wasn't going to improve with intensive lifestyle intervention was a print-out of my OTC CGM data. The CGM that's recommended for pre-diabetes is the Lingo:
I’ve been persuaded that metformin is appropriate for the first indication of insulin resistance that doesn’t respond to diet and exercise, because it will progress to diabetes if untreated.
Is it very difficult to appreciate impermanence of life ?
Great comment. I agree that it is always a trade off. But if we can do some simple things to live independently without any debilitating disease until we die, it may be worth it
The intent may be to live healthy without any chronic disease until we die
In my opinion, we here look at end of life / death like a battle instead of considering it to be a natural phenomenon.. and in the process we may focus way too much to win this un-winnable battle .. and in fact, it is not a battle at all .. and in the process of this focus, we may involuntarily focus on quantity and may ignore the focus on quality .. just my opinion.
Good one Ram and the last sentence is spot on! As someone who has spent nearly 30 years in traditional drug discovery and development, I find it hard to envision a 'magic pill' for longevity that can get the job done with a reasonable risk/benefit ratio - at least within our current capabilities.
Also, even if one were to demonstrate the above in say a small Phase 2a/b trial, there may be regulatory hurdles since as of today, FDA does not recognize aging as an 'indication' so one wonders how to go about designing a pivotal trial. Of course, above applies for only new chemical or biological entities i.e., no prior FDA approval for any other indication.
Having said this, I think there may be opportunities in future for a narrow range/applications say specifically for cardiometabolic or immune function or musculoskeletal etc. Of course, they too would have to be rigorously tested before we have the confidence for routine clinical use.
To underscore the last comment, a recent paper on both benefits and risks for calorie restriction makes the point quite well as in a future longevity drug may face the same in terms of trade offs IMO.
https://www.nature.com/articles/s41574-025-01111-1
Thank you for your in-depth look at the business of selling hope. I've linked to your article in an update of my tongue-in-cheek post about mythical "Life Extension Pills."
https://drmick.substack.com/p/life-extension-pills
Thank you Dr. Skolnick. Dr. William Bestermann has been a strong advocate of metformin for diabetes and metabolic dysfunction, and is probably the only true viable candidate for longevity. Hope we get some early results from the TAME trial. I have always wondered if metformin is safe for pre-diabetes and people who are iffy in their blood sugar and whether it would work well for them (since I am one of those people).
BTW, When my HbA1c passed the upper limit of normal for the first time, I asked my PCP if he would prescribe metformin, and he agreed to without any hesitation. I’ve been taking the 500 mg XR tablets bid pc with no ill effects, and had a decisive lowering of my HbA1c. I’m anticipating all the other metabolic health benefits Dr. Bestermann describes in detail.
Really useful Dr. Skolnick. When my Hb1Ac passed normal a while back but now it is lower than the guideline ( just barely). I am thinking of requesting my PCP for a prescription.
What convinced me, and my PCP, that my HbA1c wasn't going to improve with intensive lifestyle intervention was a print-out of my OTC CGM data. The CGM that's recommended for pre-diabetes is the Lingo:
https://www.hellolingo.com
I’ve been persuaded that metformin is appropriate for the first indication of insulin resistance that doesn’t respond to diet and exercise, because it will progress to diabetes if untreated.