TABLE 1.
Summary of major animal studies and clinical trials about the effects of metformin
| Study | Organisms | Application Scheme | Effect |
|---|---|---|---|
| Life extension effect | |||
| Slack (2012) 68 | Fruit flies | 1,10,100 mM, every day |
1–10 mM, no effect on survival; >10 mM, lifespan decrease Increase mean lifespan by 18%, 36%, 3% |
| Cabreiro (2013) 16 | C elegans | 25, 50, 100 mM, every day | Increase mean lifespan by 14%, 6%, 0% |
| Martin‐Montalvo (2013) 17 | Mice | 100 mg/kg, every day, started at 3, 9 or 15 months | 0.1%, lifespan increase by 5.83%; 1%, lifespan decrease by 14.4% |
| Zhong (2017) 15 | Human | Initial dose: 750 mg/day; increased weekly up to 1500 or 2250 mg/day for 3–12 weeks |
Increase in AMPK phosphorylation; Decreased tumor cell proliferation; Decreased H19 levels; Increased methylation in genes H19, DMRTA2, KCNG2, PSMD10, TRA2A |
| Kulkarni (2018) 82 , 86 | Human | Metformin and placebo in either order each for 6 weeks with a 2‐week washout period in between. Patients took 1–2 metformin/placebo capsules per day | Metformin influenced genes and pathways related to metabolism, collagen, mitochondria, and DNA repair |
| Pryor (2019) 13 | C elegans | Metformin was supplemented in cell culture at 6.25, 12.5, 25, 50, 100 mM | Decreased lipid droplet size and abundance and increased peroxisome abundance |
| Anticancer effect | |||
| Mitsuhashi (2014) 41 | Human | 1500–2250 mg/day, for 4–6 weeks | Inhibited endometrial cancer cells grow in vivo |
| Anisimov (2011) 39 | Mice | 100 mg/kg‐bodyweight starting at the age of 3, 9, and 15 months | Delayed tumor onset by 22% and 25% respectively at the age of 3 and 9 months |
| H. P. Chen (2013) 44 | Human | Based on the condition of patients with type 2 diabetes mellitus | Hepatocellular carcinoma risk decreases |
| Reduce cardiovascular disease risk | |||
| Lexis (2015) 35 | Human | ST‐segment elevation myocardial infarction (STEMI) patients, 500 mg twice daily, for 4 months | Cardiovascular risk decreases |
| Goldberg (2017) 36 | Human | 850 mg twice daily, for over 3.2 years | Coronary atherosclerosis risk decreases |
| Karnewar (2018) 28 | Mice | 50 mg/kg‐bodyweight for 14 months |
Ameliorated age‐related atherosclerosis; Significantly reduced macrophage recruitment and inflammatory cytokines |
| Kanamori (2019) 31 | Mice | 200 mg/kg‐bodyweight per day for 4 weeks | Partially reversed left ventricular dilatation caused by δ‐sarcoglycan deficiency |
| Griffin (2018) 83 | Human | Up to 500 mg metformin tablets (Glucophage®) per day. Participants followed up to 0.99 years (SD 0.3 years) | Small improvements in glycated hemoglobin, estimated glomerular filtration rate, LDL cholesterol. Reduced vitamin B12 level |
| Anti‐Alzheimer's disease effect | |||
| Chen (2009) 58 | Mice | 2–5 mg/ml for 6 days | Both intracellular and extracellular Aβ species increases |
| Li (2012) 59 | Mice | 200 mg kg−1 day−1 for 18 weeks | AD‐like biochemical changes decrease |
| Koenig (2017) 56 | Human | Metformin or placebo for 8 weeks | Executive functioning improves |
| Anti‐Parkinson's disease effect | |||
| Katila (2017) 66 | Mice | 200 mg kg−1 day−1 for 7 days | Metformin provides neuroprotection against MPTP neurotoxicity |