Inventory of various new discoveries of metformin😎😎😎

Metformin is an anti-diabetic drug and a classic oral hypoglycemic agent. Since its inception in 1957, it has been used clinically for more than 60 years. It is currently one of the most widely used oral hypoglycemic drugs in the world. Even though there are many new hypoglycemic drugs, metformin is still the primary drug for type 2 diabetes.

Metformin was born in 1929 and originated from galega officinalis. In 1957, French diabetologist professor Jean Sterne first used metformin for clinical hypoglycemic reduction. Then its application value is still being discovered. Let us take a look at what new discoveries have been made recently.

1. Cancer

Acidic phospholipids play an important role in regulating electrostatic membrane association of programmed cell death ligand 1 cytoplasmic domain (PD-L1-CD). Metformin can competitively dissociate PD-L1-CD from the membrane and affect the stability of PD-L1. This revealed that the molecular mechanism of metformin's anti-tumor effect and provided new ideas for related immunotherapy targeting PD-L1.

There are many studies that supporting metformin can decrease the risk or improve the symptoms of cancer patients. Such as esophageal squamous cell cancer, pancreatic cancer, primary bone cancer.

2. Obstetrics & Gynecology

a. Improve neonatal obesity

    Metformin has many benefits for mother's blood glucose and neonatal obesity, including improved blood glucose, reduced caesarean section, reduced mother's weight, lower insulin requirements,  lower birth weight and obesity measurements of newborns.

b. Prevent adverse pregnancy outcomes in patients with polycystic ovary syndrome

    Metformin can prevent late period abortion and premature birth in women with polycystic ovary syndrome.

3. Metabolic diseases

Metformin can improve the metabolic status of patients treated with systemic glucocorticoids. It can not only reverse the metabolic complications caused by the use of systemic glucocorticoids, but also reserve the anti-inflammatory effects of glucocorticoids. It benefits many patients taking systemic glucocorticoids.

4. Cardiovascular System

 a. Heart failure

    Non-diabetic heart failure patients with reduced ejection fraction (HFrEF) use metformin to reduce myocardial oxygen consumption and improve myocardial efficiency.

b. Left ventricular hypertrophy

    Metformin treatment significantly reduced the left ventricular mass index. Patients taking metformin reduced left ventricular thickening by two time less. In addition, metformin also reduced blood pressure, oxidative stress, and weight. Metformin has the potential to improve cardiovascular health.

c. Air-pollution-induced thrombosis

    Atmospheric particulate matter can induce alveolar macrophages to release pro-inflammatory factors including interleukin 6 (IL-6), leading to arterial thrombosis and death.

    Metformin blocks the mitochondrial electron transport and inhibits the production of reactive oxygen species, thereby blocking the release of IL-6 and inhibiting the formation of arterial thrombosis. This confirms that metformin can be used as a potential therapeutic drug to prevent cardiovascular diseases caused by air pollution.

5. Nervous system

a. Cognitive and nerve recovery after brain tumor surgery

    For children with brain tumor patients who have received craniocerebral radiotherapy, metformin can significantly improve their statement memory and working memory function, repairing white matter damage. Metformin is also safe and tolerable in this population.

b. Multiple Sclerosis

    After treatment with metformin, oligodendrocyte precursor cells can restore their response to the signal of promoting-differentiation, promote the regeneration of nerve myelin. This is useful for the treatment of central nerve demyelination such as multiple sclerosis.

c. Cognitive decline and dementia

    Patients with type 2 diabetes who take metformin have slower cognitive decline and a lower risk of dementia.

6. Locomotor system

a. Osteoarthritis

    Metformin can prevent the occurrence and development of osteoarthritis, alleviate the pain sensitivity associated with osteoarthritis in mice. Its protective effect on cartilage is mainly through the activation of AMPK signals.

b. Intervertebral disc degenerative disease

    Metformin can promote the release of small extracellular vesicles of mesenchymal stem cells, increase the level of proteins that regulate cell proliferation in the vesicles, and can optimize the application effect of extracellular vesicles in the regeneration and repair of intervertebral discs.

7. Digestive system

Metformin stimulates bile secretion in the intact liver, but this drug can also cause severe damage to bile acid secretion.

8. Infection

a. COVID-19

   Metformin inhibits the activation of NLRP3 inflammasomes and the production of IL-1β in cultured macrophages and alveolar macrophages, as well as the secretion of inflammasome-independent IL-6, thereby attenuating lipopolysaccharide and COVID-19 induced acute respiratory distress syndrome. Metformin can be a potential treatment for severely patients with COVID-19 and other induced acute respiratory distress syndrome.

b. HIV

    Metformin reacted on mitochondrial respiratory chain complex-I and inhibit the oxidative phosphorylation (OXPHOS) pathway. It inhibited the replication of human CD4⁺ T cells and HIV-1 virus in humanized mouse models. It revealed that metformin and others OXPHOS pathway inhibitors may be an adjunct to treat AIDS.

👉Metformin has also anti-aging effect. Most effects still are at the research stage and may not be used on treatment. Therefore, metformin still deserves more in depth research.