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Metformin + rapamycin

Metformin + rapamycin has been studied in 4 papers since 2016: none in people yet, 4 in animals. The research so far is in animals. The newest paper, Aug 19, 2022: “Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice”.

Intervention

4 papers study it5 findingsUpdated

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

  • 2 independent labs in 1 country
  • Funders: National Institute on Aging and others
  • Animals4

What did mouse lifespan tests of Metformin + rapamycin find?

NIA ITP

The NIA Interventions Testing Program ran 1 arm in 2011; median lifespan changed by +23%.

What did studies of Metformin + rapamycin find?

4

Studies of Metformin + rapamycin measured 4 outcomes; the most studied are insulin sensitivity (1 study), complications of metabolic syndrome (1) and mitochondrial protein synthesis (1).

Insulin sensitivity

upin mice1

1 study

  1. Metformin + rapamycin improves insulin sensitivity in mice.

    “combination treatment reversed effects of rapamycin on markers of hepatic insulin resistance and normalized systemic insulin sensitivity”

    Animalstype 2 diabetesdietmales

    Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice

    Aging cell

Complications of metabolic syndrome

upin mice1

1 study

  1. Metformin + rapamycin improves complications of metabolic syndrome in mice.

    “combination treatment with metformin ameliorates negative effects of rapamycin while maintaining its benefits”

    Animalspolygenic type 2 diabetic micedietmales

    Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice

    Aging cell

Mitochondrial protein synthesis

downin mice1

1 study

  1. Metformin + rapamycin decreases mitochondrial protein synthesis in mice.

    “RAP+MET decreased mitochondrial protein synthesis in young females.”

    Animalsin whole brainbrain8 weeksfemales

    Brain Protein Synthesis Rates in the UM-HET3 Mouse Following Treatment With Rapamycin or Rapamycin With Metformin

    The journals of gerontology. Series A, Biological sciences and medical sciences

More on Mitochondrial protein synthesis

Lifespan

upin mice1

1 study

  1. Metformin + rapamycin extends lifespan in mice.

    “Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit”

    Animals0.1% metformin with 14 ppm rapamycin

    Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer

    Aging cell

What is Metformin + rapamycin linked with?

1

Studies link Metformin + rapamycin with 1 measure, most often protein synthesis (1 study).

protein synthesis

mixedin mice1

1 study

  1. Metformin + rapamycin is associated with protein synthesis in mice.

    “adding Met yielded more uniform effects between tissue and sex.”

    Animalsliver and skeletal muscle8 weeks

    Sex differences in changes of protein synthesis with rapamycin treatment are minimized when metformin is added to rapamycin

    GeroScience

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