Table 1.

Preclinical and clinical results of metformin in targeting aging and aging-related diseases.

Aging and aging-related diseases		Preclinical and clinical results
Aging and lifespan		Regulate the metabolism of HEK293T through lysosomal pathway 20; Extend the lifespan of C. elegans and mice 20, 21; Reduce all-cause mortality 17-19.
Diabetes mellitus		Change the redox state of liver cells and reduce hepatic gluconeogenesis 93; Reduce blood glucose in mice 92; Improve blood glucose control and lipid concentration in patients with non-insulin-dependent diabetes mellitus (NIDDM) 24, 181.
Degenerative musculoskeletal diseases	Osteoporosis	Enhance the differentiation and mineralization of osteoblast and inhibits osteoclast differentiation, prevent bone loss in ovariectomized rats 182, 183; Metformin is associated with a lower risk of fracture 28, 29.
	Osteoarthritis	Inhibit the expression of inflammatory factors, matrix metalloproteinases and hypertrophy markers in chondrocytes through bone marrow stromal stem cells in co-culture model 33, 36; Delay the progression of osteoarthritis and reduce pain in primate and mice with osteoarthritis 35, 36; Protect joint by anti-inflammatory, regulating skeleton and reducing weight 31, 33, 34.
	Intervertebral disc degeneration	Protect nucleus pulposus cells against apoptosis and senescence or exert an anti-inflammatory effect; Reduce local mechanical hyperalgesia in the nucleus pulposus and annulus fibrosus 39, 40.
	Other bone disorders	Increase glycolytic activity and decrease the expression of inflammatory factors primary synovial fibroblast 43; Decrease the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats 44; Prevents against oxidative stress-induced senescence in human periodontal ligament cells 45; Inhibit the ossification and inflammation of ankylosing spondylitis fibroblasts 46; Inhibit the proliferation and metastasis of osteosarcoma cells 47.
Cardiovascular disease	Coronary heart disease	Protect hyperglycemia-induced endothelial impairment 184; Reduce coronary endothelial dysfunction and early progression of coronary plaque 49, 51.
	Heart failure	Reduce myocardial oxygen consumption and left ventricular mass index, left ventricular mass, office systolic blood pressure and oxidative stress in patients 53-56.
	Heart attack combined with pulmonary hypertension	Benefit rats in a rodent model of metabolic syndrome and pulmonary hypertension associated with heart failure with preserved ejection fraction 55, 56.
Neurodegenerative diseases	Alzheimer's disease	Prevent patients from Alzheimer's disease60, 61 or increase the risk of it 62, 63.
	Huntington's disease	Rescue the motor and neuropsychiatric phenotypes of Huntington's disease in zQ175 knock-in mouse 185.
	Parkinson's disease	Reduce the risk of Parkinson's disease 64, or increase the risk of PD in T2D patients65.
Obesity and other metabolic abnormalities	Obesity	Inhibit adipogenesis in adipocytes 46; Prevent obesity in mice 82, 83 and rats 84; Promote weight loss in patients who gain weight as a result of antipsychotic treatment 81.
	Fatty liver disease	Improve fatty liver disease, reversing steatosis and aminotransferase abnormalities 97.
Other diseases	Polycystic ovary syndrome	Induce ovulation in women with the polycystic ovary syndrome 186.
	Chronic kidney disease	Metformin could have benefits on kidney disease progression and may lower the risk of death 187.
	COVID-19	Reduce the Mortality of patients with COVID-19 107, 108.
	Hidradenitis suppurativa	Metformin is an effective treatment option for hidradenitis suppurativa 108.