Metformin plus rapamycin dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
Nobody has tested this pair in people. In mice fed both from 9 months, typical lifespan rose 23 percent in both sexes. But metformin alone did nothing in the same run. There was no rapamycin-only group to compare with. And the mouse program's own paper says the extra gain over earlier rapamycin-only runs did not pass
Evidence grade for Metformin plus rapamycin: Preliminary. The rule: studied in people, but no published study has had people take it. The sum on this page: 2 registered with no result. A grade counts how much has been done to people, not whether it works.
- People given it
- 0
- Human studies
- 0
- Found nothing
- 0
Dose
No human dose established
No published study on this page has given this compound to people and reported a result.
2 registered with no result
2 effects reported, 2 unwanted, by people using it, not a trial
Goal pages: Muscle and strength, Brain, memory and mood, Ageing and longevity, Injury, healing and recovery, Immune system and inflammation, Gut health
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
This page is about taking metformin and rapamycin together. Both are prescription drugs used for other things. Some people stack them to live longer, after a mouse study. Nobody has tested the pair in people.
What people take it for
- A longer life.
- The belief that the two drugs boost each other.
What studies in people showed
Nobody has tested the pair in people. One study of 30 people gives both drugs plus four other things at once, so it cannot tell what did what. It has no results yet. Another planned study never signed anyone up. Now mice. Mice on both drugs lived about 23 percent longer. But metformin alone did nothing in the same run. There was no group on rapamycin alone. Next to older rapamycin runs, the extra gain could have been chance.
What people report
Reports, not study results
The good
- We have not collected user reports on this pair yet.
The bad
- Rapamycin can weaken the immune system, cause mouth ulcers, and change blood sugar and fats.
- Metformin can upset the gut, lower vitamin B12, and blunt what you gain from exercise.
Where these come from: The side effects are the known risks of each drug, listed on this page. We have no user reports on the pair.
My bottom line
The mouse gain looks like rapamycin doing the work. Metformin can blunt what you get from training, and I care about muscle. I would not stack these without a doctor and blood work.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Metformin plus rapamycin has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Lasting longer, staminano headcount stated · 1 study
- Cell energy and mitochondriano headcount stated · 1 study
- Inflammationno headcount stated · 1 study
- Memory and thinkingno headcount stated · 1 study
Animal and lab work, not yet tested in people
Real results, but from animals or cells, not people. What works in a mouse often does not work the same way in a person. This is an approved medicine. So the missing study in people is for this use, not for the drug. Drug makers paid to test it for what it is approved for. The record on this one is set out below.
- Living longer2 animal or lab studies
31 of the 36 indexed goals have no study of any kind behind Metformin plus rapamycin
No study in people, animals or cells on this page reports a result for these. That does not prove Metformin plus rapamycin does nothing for them. It does mean anything you have heard about Metformin plus rapamycin and one of these did not come from a study cited here.
Show full evidence
What is Metformin plus rapamycin?
Nobody has tested this pair in people. In mice fed both from 9 months, typical lifespan rose 23 percent in both sexes. But metformin alone did nothing in the same run. There was no rapamycin-only group to compare with. And the mouse program's own paper says the extra gain over earlier rapamycin-only runs did not pass its standard test.
This page is about one group in one mouse experiment. People across the longevity world cite it as proof that metformin and rapamycin boost each other. The paper that reports it says something more careful. Both drugs have their own pages on this site. This one is about what happens when they are combined.
In people, no trial has tested the two drugs together. Rapamycin has small human studies on staying healthy with age. Metformin has a very large diabetes record and a stalled ageing trial. Both are on their own pages. Two registered studies come close, and neither tests the pair. A 2022 early study of metformin, dasatinib, rapamycin and five supplements was withdrawn before anyone joined. A 30 person early study by an online prescriber has been running since 2025. It gives rapamycin, metformin, low-dose naltrexone, NAD+ up the nose and a house-brand supplement all together. It measures fitness, thinking and an inflammation score, and has no results yet. Neither study could pull apart what either drug did.
In mice, the NIA lifespan program's 2011 run fed metformin at 1,000 ppm (0.1 percent of the food) from 9 months, alone and with rapamycin at 14 ppm. Metformin alone did not clearly extend lifespan. Typical (median) male lifespan was 835 days against 780 (7 percent more, could be chance). Survival to old age was 2 percent lower. Typical female lifespan was 872 days against 874, no change. The pair extended typical lifespan 23 percent in males (959 days) and 23 percent in females (1,078 days). Survival to old age rose 10 percent in males and 17 percent in females. The program had no rapamycin-only group in that run. It compared against earlier runs that gave the same rapamycin dose alone. The authors wrote that the male result was "suggestive of an added benefit". They also said the apparent boost did not pass their standard test. It only passed in a looser test that did not account for the three labs. The program's 2020 rapamycin paper says it again: the pair's survival results "were not significantly higher than those noted in earlier experiments using the same dose (14.7 ppm) of rapamycin by itself". A 2024 second look with the Gehan test found metformin alone just passed in males. A 2022 review that pooled studies found metformin did not make mice live longer across the published record.
Both drugs are approved prescription medicines for other uses. Taking them together for ageing is off-label everywhere.
How does Metformin plus rapamycin work?
Rapamycin blocks mTORC1, a growth switch. At the doses used in mice, it lowers cancer rates, changes immune function and shifts metabolism in ways that differ from eating less. Metformin blocks part of the mitochondria's energy chain (complex I). It turns on an energy sensor called AMPK in some tissues, and it cuts the sugar the liver releases. The idea behind combining them was that metformin might soften the high blood sugar and insulin resistance rapamycin causes in mice. The two also work on partly separate nutrient sensors. The mouse paper reports lifespan and does not test that idea. It had no rapamycin-only group, so it cannot say whether metformin added anything. The case for a boost rests on guesses from each drug's own record. In people there are no data on the pair. How each drug acts in the body is on its own page.
What have studies in people found about Metformin plus rapamycin?
None for the pair. No trial has given metformin and rapamycin together to people as a two-drug test. One early study gives both plus four other things to 30 people, with no results yet. Another was withdrawn before anyone joined. Each drug's own human record is on its own page.
- NCT07475546: a 30 person early study run by the prescriber. It combines rapamycin, metformin, naltrexone, NAD+ and supplements. Still running, no results. It cannot say what either drug did.
- NCT04994561: a planned early study of metformin, dasatinib, rapamycin and supplements. Withdrawn, nobody joined.
- No study has checked whether the two drugs change each other's levels in the body in people.
- Rapamycin alone: small studies in older adults (see the rapamycin page). Metformin alone: decades of diabetes trials, and a 21 year diabetes prevention follow-up that found no effect on deaths (see the metformin page).
What this does not tell you: There is no human evidence for or against this pair. Anyone taking both for ageing is acting on one mouse run. That run lacked the group needed to show the pair beats rapamycin alone. On top of that come each drug's own risks. For rapamycin: a weaker immune system, mouth ulcers and effects on blood sugar and fats. For metformin: gut problems, lower vitamin B12, and a trial signal that it blunts what the body gains from exercise.
The state of the research
The National Institute on Aging runs a mouse lifespan program called the Interventions Testing Program. It tests each compound at three labs at the same time: The Jackson Laboratory, the University of Michigan and UT Health San Antonio. The mice are a mixed breed, so a result is less likely to be a quirk of one strain. Males and females are both tested and judged separately. The three labs' results are then pooled. Every result gets published, whether or not the compound worked. It runs on public money from the National Institute on Aging, with no drug company money. The 2011 run tested metformin at 1,000 ppm alone and with rapamycin at 14 ppm, both from 9 months. Metformin alone did nothing clear in either sex. The pair gave a 23 percent gain in typical (median) lifespan in both sexes, with strong gains in survival to old age. The flaw, which the program states plainly, is that the run had no rapamycin-only group. So the claim that metformin added anything rests on comparing with rapamycin runs from earlier years. By the standard test, that comparison did not pass in males. It passed only when the analysis stopped accounting for the three labs, which is not the test they planned in advance. In females the authors call any added effect small. The program's own later rapamycin paper says the pair's survival was not clearly higher than the same rapamycin dose alone in earlier runs.
The honest one-line reading: rapamycin works, and adding metformin did not clearly beat rapamycin alone. That is weaker than the claim going around, and it is what the original paper says. It also does not prove metformin adds nothing. A proper test would need single-drug groups run at the same time. The program has since run a pair test for rapamycin plus acarbose, and the same problem came back, because that run also lacked single-drug groups. Nobody will pay to test two cheap generic drugs in people, so no company trial will settle it.
The evidence, in charts
Fig. 1a · how many people
2studies in people cited, but none says how many people took part
number of people not stated
We do not draw a total, because none of the studies in people on this page gives one. Read the sources below for what each study measured.
We read the number of people from the source lines on this page. Where a line gives no number, we count nothing for it. We do not guess.
Fig. 1b · evidence mix
2 of 8 sources here are studies in people. The rest are not.
- Study in people · done in people225%
- Animal study · done in animals450%
- Review of studies · sums up other studies225%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
The studies cover 6 different years, 2014 to 2025, counted from the list of sources on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Approved
Approved in all four countries shown. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 5 · what the molecule is
- Kind of compound
- Small molecule
- Molecule weight
- Not on file
- Half-life
- None on file
- Chain length
- None on file
No amino acid sequence is on file for Metformin plus rapamycin, which is expected: a small molecule is not built from amino acids.
The studies we cite
- Study in people2025A pilot randomized controlled study of combinatorial gerotherapeutics for healthspan improvement
The one trial testing this pair cannot tell the two drugs apart. 30 people are enrolled by AgelessRx, an online company that prescribes these drugs, and it is no longer signing people up. Every group stacks rapamycin and metformin together with low-dose naltrexone, NAD+ up the nose, glutathione on the skin and a house-brand supplement. With six things given at once, no result could be traced to either drug. Nothing has been posted.
30 participants, sponsor AgelessRx (a telehealth prescriber), active not recruiting. Arms combine rapamycin 2 to 6 mg weekly, metformin 500 mg daily, low-dose naltrexone, intranasal NAD+, topical glutathione and a proprietary supplement; primary endpoints VO2 max, a cognitive composite and an inflammation index. Cannot isolate either drug. No results posted.
- Study in people2022Pilot study of metformin, dasatinib, rapamycin and nutritional supplements in aging
This trial never happened. An early-stage study of metformin, dasatinib, rapamycin and supplements in ageing was registered by the Vitality in Aging Research Group and then withdrawn with nobody enrolled. Not a single person took part. A withdrawn registration is a plan, not evidence, and it should never be counted as a study of this combination.
Phase 1, Vitality in Aging Research Group. WITHDRAWN with zero participants enrolled.
- Review of studies2022Metformin has heterogeneous effects on model organism lifespans and is beneficial when started at an early age in Caenorhabditis elegans: a systematic review and meta-analysis
In animals. This review pooled lifespan studies of metformin in lab animals. Metformin did not make mice live longer. That held even with the NIA program's data left out. Independent university researchers wrote it.
Pooled model-organism lifespan data: metformin was not associated with mouse lifespan extension, and the null persisted when ITP data were excluded. Independent academic review.
- Review of studies2025Emerging uncertainty on the anti-aging potential of metformin
A review by one of the mouse program's lab heads and a drug-safety researcher. It lays out why the animal and human case for metformin as an anti-ageing drug has grown weaker. One reason: the metformin plus rapamycin group had no rapamycin-only group run alongside it.
Review co-authored by an ITP site director and a pharmacoepidemiologist setting out why the animal and observational human case for metformin as an anti-ageing drug has weakened, including the combination arm's lack of a contemporaneous rapamycin control.
- Animal study2016Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an alpha-glucosidase inhibitor or a Nrf2-inducer
In mice. The NIA mouse lifespan program's 2011 run. Metformin alone at 1,000 ppm from 9 months did nothing clear in either sex. Metformin plus rapamycin at 14 ppm made typical lifespan 23 percent longer in both sexes. Survival to old age rose 10 percent in males and 17 percent in females. There was no rapamycin-only group. Against earlier rapamycin-only runs, the extra male gain only hinted at a boost and did not pass the standard test. Public NIA money paid for it.
ITP 2011 cohort. Metformin 1,000 ppm from 9 months alone: male median +7 percent (p = 0.35), 90th percentile -2 percent; female 0 percent; not significant. Metformin plus rapamycin 14 ppm: male median 959 versus 780 days (+23 percent), 90th percentile +10 percent; female median 1,078 versus 874 days (+23 percent), 90th percentile +17 percent; all p < 0.001. No rapamycin-alone arm; comparison with historical rapamycin cohorts described as suggestive of added benefit, with the male synergy test p = 0.12 by the protocol analysis. NIA funded.
- Animal study2020Rapamycin-mediated mouse lifespan extension: late-life dosage regimes with sex-specific effects
In mice. The mouse program's own later summary says the metformin plus rapamycin survival results "were not significantly higher than those noted in earlier experiments using the same dose (14.7 ppm) of rapamycin by itself". It also reports that rapamycin at 42 ppm, started at 20 months, extended lifespan in both sexes. Public NIA money paid for it.
The ITP's own later summary: the metformin plus rapamycin survival results "were not significantly higher than those noted in earlier experiments using the same dose (14.7 ppm) of rapamycin by itself". Also reports rapamycin at 42 ppm from 20 months extending lifespan in both sexes. NIA funded.
- Animal study2014Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction
In mice. Rapamycin alone at 42 ppm made typical lifespan 23 percent longer in males and 26 percent longer in females. The oldest mice lived longer too, in both sexes. Females gained more at every dose. This shows rapamycin alone can match the pair's 23 percent when its dose is tripled. Public NIA money paid for it.
Rapamycin alone at 42 ppm extended median lifespan 23 percent in males and 26 percent in females, with maximal lifespan increased in both sexes, and females gained more at every dose. The benchmark showing rapamycin alone can match the combination's 23 percent when its dose is tripled. NIA funded.
- Animal study2024The Gehan test identifies life-extending compounds overlooked by the log-rank test in the NIA Interventions Testing Program: metformin, enalapril, caffeic acid phenethyl ester, green tea extract, and 17-DMAG
In mice. A second look at the NIA mouse lifespan program. Metformin alone at 1,000 ppm from 9 months: 148 treated males against 294 untreated ones. Typical male lifespan rose 8 percent. The standard test said that could be chance. The Gehan test, which counts early deaths more, just passed. Females showed nothing. Borderline, in a look at 132 comparisons with no adjustment reported for running so many. Public NIA money paid for it.
Metformin alone, 1,000 ppm from 9 months, 148 males against 294 controls: median +8 percent, log-rank p = 0.35, Gehan p = 0.0495, proportional hazards violated. No female effect. Borderline, in a 132-comparison reanalysis with no multiplicity correction reported. NIA funded.
Common questions
Has Metformin plus rapamycin been tested in people?
Not in a completed trial cited here. 2 registered with no result. Nobody has tested this pair in people. In mice fed both from 9 months, typical lifespan rose 23 percent in both sexes. But metformin alone did nothing in the same run. There was no rapamycin-only group to compare with. And the mouse program's own paper says the extra gain over earlier rapamycin-only runs did not pass
What is the Metformin plus rapamycin dosage?
No human dose established. No published study on this page has given this compound to people and reported a result. 2 registered with no result
Is Metformin plus rapamycin FDA-approved?
Both drugs are FDA-approved for other uses (metformin for type 2 diabetes, rapamycin as sirolimus for transplant rejection and other uses). The combination is not approved for anything. The lifespan result is in mice, and the study did not test rapamycin alone at the same time to compare.
Is metformin plus rapamycin synergistic?
The mouse program's own paper does not claim that. The pair extended typical mouse lifespan 23 percent in both sexes. But the run had no rapamycin-only group. Compared with earlier rapamycin-only runs, the extra male gain did not pass the standard test. The program's 2020 paper says the pair was not clearly better than the same rapamycin dose alone.
Did metformin alone extend lifespan in that experiment?
No. Typical male lifespan was 7 percent higher, which could have been chance, and survival to old age was 2 percent lower. Females showed no change. A 2024 second look with the Gehan test said the male effect just passed. That is a borderline result, in a study that ran a very large number of comparisons.
Has anyone tested the combination in people?
No. One 30 person early study gives both drugs together with four other things, and it cannot pull them apart. Another planned study was withdrawn before anyone joined. Nobody has studied how the two drugs affect each other's levels in the body.
What dose did the mice get?
Metformin at 1,000 ppm in food, which is 0.1 percent of the diet, and rapamycin at 14 ppm, from 9 months of age for life. In a separate run, rapamycin alone at three times that dose (42 ppm) gave 23 to 26 percent gains in typical lifespan without metformin.