Head-to-head

Canagliflozin vs Metformin

The two most talked-about 'off-label longevity' diabetes drugs — one has a human aging trial in progress that still hasn't reported, the other has only mouse data.

Canagliflozin

Invokana

FDA-approved

FDA-approved SGLT2 inhibitor with real cardiovascular and renal outcome trials (CANVAS, CREDENCE) — but the longevity claim rests entirely on a 14% median-lifespan extension in male-only NIA ITP mice; no human longevity trial exists, and the drug carries real risks (amputation, Fournier's gangrene, euglycemic DKA) that apply the same whether it's prescribed for diabetes or taken off-label for aging.

Full Canagliflozin evidence review

Metformin

Clinical data

An approved diabetes drug with an intriguing longevity hypothesis — but the dedicated aging trial (TAME) is still pending; longevity in healthy people is unproven.

Full Metformin evidence review

Side by side

	Canagliflozin	Metformin
Marketed for	Type 2 diabetes (approved); explored off-label for longevity on mouse ITP data	Longevity, healthspan, metabolic aging
Evidence grade	FDA-approved	Clinical data
Family	Metabolic / AMPK	Metabolic / AMPK
Key human source	Miller 2020 NIA ITP, JCI Insight	MILES/TAME rationale 2014

marks a row where the two differ. Evidence grades come from our evidence matrix, which grades each molecule on the human data for the use it is marketed for.

Our verdict

Metformin's longevity case rests on an observational survival signal and mechanistic plausibility, with the dedicated human aging trial (TAME) still not reporting results after years — so its longevity claim is not more human-proven than canagliflozin's, just older and more discussed. Canagliflozin's case is entirely mouse-only ITP data, more recent, and specifically male-skewed. Both are approved for diabetes with real outcome trials in that indication; neither has ever been shown, in a human trial, to extend healthy lifespan.

Canagliflozin fits if

You're drawn to the more recent, replicated ITP signal and are comfortable with SGLT2-class risks (amputation, genital infection, euglycemic DKA).

Metformin fits if

You want the more-discussed, longer-track-record option, understanding that 'more discussed' isn't the same as 'more proven' — TAME hasn't reported.