Metformin + rapamycin
Metformin + rapamycin has been studied in 7 papers since 2016: none in people yet, 5 in animals, 2 in cells; 1 in the past year. The research so far is in animals and cells. The newest paper, Apr 28, 2026: “Autophagy enhancement via metformin-rapamycin combination for Z-AAT clearance”.
7 papers study it6 findingsUpdated
See all 7 papers on Metformin + rapamycin
At a glance
The findings reach mice, none yet in people. 3 independent labs in 2 countries.
None of its findings points the other way.
- 3 independent labs in 2 countries
- Funders: National Institute on Aging and others
- Animals5
- Cells2
What did mouse lifespan tests of Metformin + rapamycin find?
NIA ITPThe NIA Interventions Testing Program ran 1 arm in 2011; median lifespan changed by +23%.
What did studies of Metformin + rapamycin find?
6Studies of Metformin + rapamycin measured 6 outcomes; the most studied are clearance of aggregated Z-variant SERPINA1 (1 study), insulin sensitivity (1) and sex and tissue differences in rapamycin-induced protein synthesis changes (1).
Clearance of aggregated Z-variant serpina1
upin reviews1
1 study
Clearance of aggregated Z-variant serpina1
upin reviews1
Metformin + rapamycin increases clearance of aggregated Z-variant SERPINA1.
“synergistically enhancing autophagosome formation and clearance of aggregated Z-variant SERPINA1 through LC3B-II and SQSTM1/p62-mediated selective autophagy”
ReviewLow-dose metformin and micro-dose rapamycin
Autophagy enhancement via metformin-rapamycin combination for Z-AAT clearance
Zenodo (CERN European Organization for Nuclear Research)Preprint
Insulin sensitivity
upin mice1
1 study
Insulin sensitivity
upin mice1
Metformin + rapamycin improves insulin sensitivity in NcZ10 mice with inherent insulin resistance.
“Importantly, the combination treatment reversed effects of rapamycin on markers of hepatic insulin resistance and normalized systemic insulin sensitivity in this inherently insulin-resistant model.”
Animalsin NcZ10 mice with inherent insulin resistancemales
Aging cell
Sex and tissue differences in rapamycin-induced protein synthesis changes
downin mice1
1 study
Sex and tissue differences in rapamycin-induced protein synthesis changes
downin mice1
Metformin + rapamycin decreases sex and tissue differences in rapamycin-induced protein synthesis changes in mice (compared with rapamycin alone).
“adding Met yielded more uniform effects between tissue and sex”
Animalscompared with rapamycin aloneliver and skeletal muscle8 weeksmale and females
GeroScience
Mitochondrial protein synthesis rate
downin mice1
1 study
Mitochondrial protein synthesis rate
downin mice1
Metformin + rapamycin decreases mitochondrial protein synthesis rate in mice.
“RAP+MET decreased mitochondrial protein synthesis in young females”
Animalsbrain8 weeksfemales
The journals of gerontology. Series A, Biological sciences and medical sciences
Oxidative stress and ROS signaling
downin rats1
1 study
Oxidative stress and ROS signaling
downin rats1
Metformin + rapamycin decreases oxidative stress and ROS signaling in rats (significantly augmented effect compared with individual drugs; synergistic response).
“the cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions”
Animalsin aged rats (24 months) with age-dependent oxidative stress; synergistic compared with either drug aloneerythrocytes and plasma0.5 mg/kg body weight rapamycin and 300 mg/kg body weight metforminmales
Rejuvenation research
Lifespan
upin mice1
1 study
Lifespan
upin mice1
Metformin + rapamycin extends lifespan in mice (combined treatment; benefit suggested by historical comparison with rapamycin alone).
“Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan”
Animalscombined treatment; benefit suggested by historical comparison with rapamycin alonemetformin 0.1%, rapamycin 14 ppmlifelong
Aging cell