Rapamycin vs Metformin for Longevity: The Evidence
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[Longevity · Comparison]

Rapamycin vs metformin: what does the aging research show?

Approved uses · Mouse lifespan · Human trials · Safety

Short answer: Neither drug is approved for aging. Rapamycin (sirolimus) is approved for kidney transplants and a rare lung disease; metformin for type 2 diabetes.12 In mice, rapamycin extended lifespan in both sexes, while metformin alone did not in the largest multi-site test.34 Human aging trials of each are small, and we found no trial comparing them in people.

How do rapamycin and metformin compare for aging research?

Approved uses from the US labels; aging findings from published studies. Use for aging is off-label for both.
Rapamycin (sirolimus)Metformin
Approved forPreventing rejection in kidney transplants (age 13 and up); lymphangioleiomyomatosis (LAM)1Blood sugar control in type 2 diabetes2
How it worksmTOR inhibitor that suppresses the immune system1Biguanide; in mice it raised AMPK activity25
Half-lifeAbout 62 hours (repeated dosing, transplant patients)1About 6.2 hours in plasma2
Boxed warningInfections and lymphoma or other cancers from immune suppression; not for liver or lung transplants1Lactic acidosis2
Mouse lifespan (NIA testing program)Started at 600 days: +14% (females) and +9% (males) at 90% mortality3Alone at 0.1% of diet: no significant lifespan gain4
Other mouse studyNot covered hereOne lab: longer healthspan and lifespan in male mice at 0.1%; 1% was toxic5
Human aging trials foundPEARL: 48 weeks, 5 or 10 mg weekly; main outcome (visceral fat) unchanged66-week crossover in 14 older adults (gene activity); 14-week exercise trial (less muscle gain)78

Reviewed . Half-life figures are shown only where the value Dose Track uses agrees with the cited source.

What did mouse studies find?

The National Institute on Aging's testing program runs each compound at three sites in genetically mixed mice. Rapamycin started at 600 days of age extended both median and maximum lifespan in males and females.3 In the same program, metformin alone at 0.1% of the diet did not significantly extend lifespan, but metformin plus rapamycin did; the authors judged an added benefit by comparing with earlier rapamycin-only studies, not within one experiment.4

A separate single-lab study found metformin at 0.1% of the diet, started in middle age, extended healthspan and lifespan in male mice, while 1% was toxic.5

What has been tested in people?

  • Rapamycin (PEARL): healthy adults took placebo, 5 mg or 10 mg compounded rapamycin once a week for 48 weeks. Side effects were similar across groups. Visceral fat, the main outcome, did not change; lean mass and pain improved in women on 10 mg. The authors work for the company that ran it.6
  • An mTOR inhibitor and vaccines: in older volunteers, everolimus (a drug related to rapamycin) improved the response to a flu vaccine by about 20%.9
  • Metformin and gene activity: 14 people around age 70 took 6 weeks each of metformin and placebo; metformin changed the activity of 647 genes in muscle and 146 in fat tissue.7
  • Metformin and exercise: in 94 healthy adults 65 and older doing 14 weeks of strength training, those on 1,700 mg a day gained less lean mass and thigh muscle than those on placebo.8

A 2016 paper described plans for TAME (Targeting Aging with Metformin), a larger trial of metformin against age-related disease.10 These are study protocols, not personalized advice; confirm any dosing with your prescriber.

What do the labels warn about?

The sirolimus label's boxed warning covers infections and lymphoma or other cancers from immune suppression. It also says grapefruit juice must not be taken with it, and live vaccines should be avoided.1 The metformin label's boxed warning is lactic acidosis, and it notes metformin can lower vitamin B12.2 These warnings come from people taking the drugs for transplants and diabetes, often at different doses from the aging studies.

More detail: metformin side effects and the Rapamycin and Metformin guides.

This page summarizes labels and published studies. It is not personalized medical advice; confirm any dose or change with your prescriber.
Metformin vs Ozempic: how do they differ?Generic daily tablet vs weekly GLP-1 pen Metformin vs Jardiance: how do the two diabetes tablets differ?Biguanide vs SGLT2 tablet, plus the combination trial Pioglitazone vs metformin: how do they compare?Insulin sensitizer vs first-line biguanide MOTS-c vs SS-31: how do they differ?Mouse-stage peptide vs an FDA-approved drug NAD+ injection vs oral NR or NMN: what do studies show?Direct NAD+ vs oral precursors

Frequently asked questions

Has rapamycin been compared with metformin for aging in people?+
Not that we found. The only direct comparison we found was in mice, where metformin alone did not extend lifespan but metformin with rapamycin did.4
Is rapamycin or metformin approved for longevity?+
No. Sirolimus is approved for kidney transplants and LAM, and metformin for type 2 diabetes. Use for aging is off-label for both.12
Does metformin interfere with exercise gains?+
In one trial of 94 adults 65 and older, those taking 1,700 mg a day during 14 weeks of strength training gained less lean mass and thigh muscle than those on placebo.8
Why is rapamycin taken weekly in longevity studies?+
The label doses sirolimus daily for transplants and LAM. The PEARL trial used 5 or 10 mg once a week; the label half-life is about 62 hours.61
Can I track rapamycin and metformin in Dose Track?+
Yes. Both are in the library; you can log a weekly rapamycin dose and daily metformin with separate reminders.

Sources

  1. Sirolimus tablets (Glenmark) prescribing information, boxed warning and sections 1, 2, 3, 5, 7 and 12.3. DailyMed, version 4 (January 2026).
  2. Metformin hydrochloride tablets (Zydus) prescribing information, boxed warning and sections 1, 2, 3, 5, 6.1, 12.3 and 14. DailyMed, version of July 2026.
  3. Harrison DE, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392-395.
  4. Strong R, et al. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell. 2016;15:872-884.
  5. Martin-Montalvo A, et al. Metformin improves healthspan and lifespan in mice. Nat Commun. 2013;4:2192.
  6. Moel M, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY). 2025;17:908-936.
  7. Kulkarni AS, et al. Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults. Aging Cell. 2018;17:e12723.
  8. Walton RG, et al. Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: a randomized, double-blind, placebo-controlled, multicenter trial (the MASTERS trial). Aging Cell. 2019;18:e13039.
  9. Mannick JB, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014;6:268ra179.
  10. Barzilai N, et al. Metformin as a tool to target aging. Cell Metab. 2016;23:1060-1065.

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