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Metformin is cheap, old and safe enough that it is the obvious candidate for a drug that slows ageing. The largest cancer trial ever run on it, in 3,649 women with breast cancer, found nothing. The trial designed to test whether it slows ageing itself has not been run.
The case for metformin rests on observational data in people with diabetes, on laboratory work on AMPK, mTOR and mitochondrial complex I, and on a small mechanistic trial. In MILES, 14 participants of about 70 took metformin and placebo for six weeks each in a randomised double-blind crossover; 647 genes were differentially expressed in muscle and 146 in fat, with changes in DNA repair, mitochondrial fatty acid oxidation and collagen pathways. That is a transcriptional signature, not a health outcome.
The outcome trial in cancer is MA.32: 3,649 people with high-risk non-metastatic breast cancer and without diabetes, randomised to metformin 850 mg twice daily or placebo for five years, with follow-up to October 2020. In the hormone receptor-positive group, invasive disease-free survival events occurred at 2.78 per 100 patient-years on metformin against 2.74 on placebo (hazard ratio 1.01, 95% CI 0.84 to 1.21, P = 0.93); deaths at 1.46 against 1.32 per 100 patient-years (hazard ratio 1.10, P = 0.47). In the receptor-negative group futility was declared at interim. Grade 3 non-haematological toxic events were more frequent on metformin (21.5 against 17.5 per cent, P = 0.003). This is an adequately sized randomised trial and it found nothing for the cancer outcome it tested.
TAME, the trial designed to test metformin as a geroprotector against a composite of age-related disease, has been proposed for a decade and has not started. So the honest position is: metformin is a good drug for diabetes, it did not improve breast cancer outcomes when properly tested, and whether it slows human ageing is unknown. It is not a reason to take it after cancer treatment, and it is not harmless: it lowers vitamin B12 and causes gastrointestinal effects in a substantial minority.
Metformin inhibits mitochondrial complex I, raising the AMP to ATP ratio and activating AMPK, which suppresses mTORC1 and gluconeogenesis. The geroprotection hypothesis is that this mimics part of the caloric-restriction response; the oncology hypothesis was that lowering insulin would slow insulin-driven tumour growth.
Query for this technology: (TITLE:"metformin" OR ABSTRACT:"metformin") AND (aging OR ageing OR geroprotector OR (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma)). Results are unfiltered search hits about Metformin as an anti-ageing drug after cancer, not a curated reading list.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship, repurposing.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Survivorship care and late-effects surveillance, HR-positive / HER2-negative breast cancer and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.
Shares What actually works after treatment, Late effects and survivorship toxicity, Survivorship care and late-effects surveillance, Survivorship and late effects are neglected and the tags rejuvenation, survivorship.