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Longevity Record

Head to head

Rapamycin vs metformin: the two repurposing candidates, compared

Last reviewed 22 August 2026 · grades regenerate automatically when the evidence changes

Rapamycin and metformin are the longevity field's two great repurposing hopes — existing drugs, decades of safety history, striking animal or observational signals. They are also both stalled at the same gate: neither has a completed randomised human trial with an ageing outcome.

Rapamycin

Prescription-only medicine

The animal case is unusually strong; the human case is unusually early. Small trials of low-dose mTOR inhibition have produced mixed results on immune function, a recent one-year safety trial reported low-dose rapamycin as generally well tolerated, and nothing in humans has measured lifespan.

Full evidence page →

Metformin

Prescription-only medicine

A proven diabetes medicine; an unproven longevity drug. Randomised evidence for benefits beyond diabetes does not yet exist, and meta-analysis of trials within diabetes found the cardiovascular case weaker than commonly assumed.

Full evidence page →

The honest verdict

Rapamycin has the better animal evidence and the more interesting human immune data — including a phase 3 failure that its enthusiasts routinely omit. Metformin has vast diabetic-population data and an inconclusive cardiovascular meta-analysis, with the TAME ageing trial still unreported. Neither currently supports off-label longevity use in healthy people.

If a genuine difference matters to a reader today, it is safety context: metformin is one of the most-prescribed drugs on earth with a well-mapped profile, while rapamycin is an immunosuppressant whose low-dose longevity regimens have only first-year safety data. That asymmetry — not efficacy, which neither has demonstrated — is the honest comparison.

Sources

Every study behind both columns, each verified against PubMed at build time.

  1. [1]Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results (2025). PMID 40188830
  2. [2]mTOR inhibition improves immune function in the elderly (2014). PMID 25540326
  3. [3]TORC1 inhibition enhances immune function and reduces infections in the elderly (2018). PMID 29997249
  4. [4]Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials (2021). PMID 33977284
  5. [5]Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes (2017). PMID 28770324

Keep reading

Rapamycin's cautionary tale →Live longevity trials →Grade your own stack →

Educational information, not medical advice. Grades are produced by our published methodology from recorded study facts; prescription decisions belong with a clinician.