Should a healthy person without diabetes take metformin to slow ageing?

What the experts say

Siim LandSelf-described anthropologist by education · health author and video essayist

No, and it may cost you the fitness gains that predict longevity

What it rests onThe 2014 observational finding that diabetics on metformin outlived non-diabetics did not control for other variables, and a 2022 reassessment found metformin associated with increased mortality in case-control pairs regardless of dose. Metformin also lowers VO2 max and may blunt hypertrophy, and both are strong mortality predictors.

Source: siimland.co ↗

David A. SinclairPhD · Professor of Genetics, Harvard Medical School

Yes, as a prescriber conversation, and he takes it himself

What it rests onHe presents metformin as an AMPK activator with the best human data of any compound he discusses, points at the observational mortality findings and the TAME trial as the test that will settle it, and treats it as a prescription decision rather than a purchase.

Source: lifespanpodcast.com ↗

Overview

Land's claim is scoped to healthy non-diabetics and, by his own following paragraph, to young ones: "at my age I have very little to gain even mechanistically". Sinclair is in his fifties. Neither is talking about people with type 2 diabetes, where both accept the drug is beneficial.

Where they agree

They agree on the exercise mechanism, which is the whole of Land's practical objection. On Huberman Lab 52, 27 Dec 2021, at 44:35, Sinclair says "If I'm going to exercise that day, I will skip the metformin", and describes reduced stamina from inhibited energy production.

He takes the same finding Land uses to decline the drug and uses it to schedule the drug. That is the real disagreement and it is narrower and more interesting than "should you take metformin".

What would settle it

TAME, or any randomised trial of metformin in non-diabetics with a mortality or incident-disease endpoint. Both sides name it. Land would additionally be moved by data showing the VO2 max and hypertrophy effects do not persist.

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