The Metformin Debate

#21

Actually I forgot there’s this paper on some GLP1-RAs extending lifespan in C. Elegans: Calcium channel blockers reduce aging rate (ARDD video) - #2 by adssx

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#22

Delay differently? SGLT2i impact spikes (i.e.effect).

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#23

Bet they will try it once oral GLP-1 agonists are available.

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#24

I am mildly concerned about posting this article as it looks like it is written by AI. However,

From the article:

Take-home synthesis (≈150 Words)

  • Rapamycin remains the lifespan champion in laboratory animals and delivers measurable immune rejuvenation in older adults, yet its influence on multi-omic aging clocks is inconsistent—sometimes slowing, sometimes neutral, and occasionally accelerating DNAm age.
  • Metformin lags on absolute lifespan in animals but shows more reproducible molecular age reversal in humans and primates, particularly within metabolic and neuro-inflammatory pathways.
  • The divergence underscores that “living longer” and “aging slower” are not interchangeable metrics. Biological clocks capture intrinsic cellular wear, whereas rapamycin’s forte may lie in systemic remodeling of immunity and metabolism that extends survival without fully rewriting epigenetic history.
  • For clinicians and start-ups, the message is nuanced: rapamycin suits short-term immune enhancement or late-life disease postponement; metformin suits chronic metabolic tuning with multi-tissue rejuvenation potential. Future trials combining mTOR modulation, AMPK activation, and next-generation GLP-1 therapies—while tracking diverse aging clocks—might finally align lifespan, healthspan, and molecular youthfulness in the same cohort.
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#25

Orforglipron appears to be becoming available from Chinese gray market sources, similar ones that are selling peptides.

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#26

After using metformin for a while I can’t say there is a discernible benefit. I mostly got it because it doesn’t interact with that enzyme that makes rapamycin more potent in the body when activated/inhibited (I forget its name.)

I’ve got some empagliflozin coming and I’m thinking I’ll remove the metformin, throw in empagliflozin and replace the metformin with berberine again.

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#27

I’ve tried berberine and metformin, and in my experience, it felt like berberine was an inferior analog to Metformin.

#28

Berberine consistently outperforms it in terms of lifespan extension.

#29

Could you reference those studies that show this? I don’t recall reading that before. I’m happy to change my mind with evidence.

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#30

Looking into it I was wrong. I’m not sure why I thought this.

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