Metformin has a new effect

Recently, the oncology journal clinical cancer research published the results of a phase II clinical study completed by researchers from Shantou University and other institutions. This paper suggests that metformin, a hypoglycemic drug, may benefit patients with esophageal squamous cell carcinoma by improving the immune microenvironment (time) in tumor lesions.

The study was designed to evaluate direct anti ESCC activity in a phase II clinical trial of low-dose Metformin (250 mg / D) in which matched ESCC specimens were analyzed before and after treatment. A follow-up study on the carcinogen induced ESCC mouse model was carried out using short-term (1 week) or long-term (12 weeks) low-dose metformin (50 mg / kg / day). The final results showed that compared with the control group, low-dose metformin did not affect the proliferation and apoptosis of ESCC tumor, but the number of B cells and T cells in the tumor site was significantly increased, the tumor inhibitory (CD11c +) and macrophages were significantly increased, while the tumor promoting macrophages (CD163 +) were significantly reduced. Metformin enhanced macrophage mediated phagocytosis of ESCC cells in vitro. In vitro basic experiments and animal experiments have shown that low-dose metformin can improve time, which shows its application prospect in esophageal squamous cell carcinoma. In search of "metformin" on the official website of SFDA, there were 310 drug approval documents involving hundreds of pharmaceutical enterprises. It is understood that China has the largest number of diabetic patients in the world.

According to the ninth edition of the global diabetes map, there are more than 116.4 million diabetic patients in China, most of whom are type 2 diabetes mellitus (T2DM). Metformin, as the first choice and whole course drug for the treatment of type 2 diabetes, is also the first choice for single drug treatment and combined treatment. According to the data from zhongmi intranet, the total market scale of metformin in China's public medical institutions, physical pharmacies and other sales terminals in 2019 is more than 6 billion yuan. The market size is also accompanied by great competition. There are not only original research drugs and reviewed generic drugs competing in the same competition, but also a large number of generic pharmaceutical enterprises are still working in the market.  But the ceiling of metformin is far from reaching: every once in a while, new research results of metformin are found: combination therapy may treat triple negative breast cancer; it can protect the stomach and reduce the risk of gastric cancer In addition, anti-aging, promoting hair growth, helping to quit smoking, anti haze and other functions have also aroused widespread concern in the industry. To some extent, the therapeutic potential of metformin is being continuously tapped, including many clinical trials that have progressed to phase II. If new indications are approved in the future, it will break through 6 billion sales volume of metformin and realize a new round of market volume.

1. Weight loss metformin is a kind of hypoglycemic drug that can reduce weight. It can increase insulin sensitivity and reduce fat synthesis. For many type 2 sugar friends, weight loss itself is conducive to stable blood glucose control. A study by the US diabetes prevention program (DPP) team showed that patients treated with metformin lost an average of 3.1 kg over a 7-8-year period in a non blinded study.

2. Anti aging effect recently, the U.S. Food and Drug Administration approved the clinical trial of "using metformin to fight aging". The reason why foreign scientists regard metformin as an anti-aging candidate drug may be that metformin can increase the amount of oxygen molecules released into cells. In principle, it seems that this can increase the body's strength and prolong its life span Long life.

3. Reversal of biological age an important news was published on the official website of nature, an international scientific and technological journal. A small clinical study in California has shown for the first time that reversing the human epigenetic clock is possible. Over the past year, nine healthy volunteers took a mixture of growth hormone and two diabetes drugs, including metformin. By analyzing the markers on a person's genome, their biological age has fallen by an average of 2.5 years.

4. Haze prevention research results show that the team led by professor Scott Budinger of Northwestern University in the United States confirmed in mice that metformin can prevent inflammation caused by haze, prevent immune cells from releasing a dangerous molecule into the blood, inhibit the formation of arterial thrombosis, and reduce the risk of cardiovascular disease.

5. Researchers from the University of Pennsylvania who assisted in quitting smoking found that long-term nicotine use can Lead to the activation of AMPK signaling pathway, which is inhibited when nicotine withdrawal occurs. Therefore, they concluded that if the AMPK signaling pathway was activated with drugs, the withdrawal reaction might be alleviated. Metformin is an AMPK agonist. When the researchers gave metformin to mice that had a nicotine withdrawal response, they found that it alleviated the withdrawal reaction in mice. Their research shows that metformin can be used to help quit smoking.

6. Pre clinical and clinical studies have shown that metformin can not only improve chronic inflammation by improving metabolic parameters such as hyperglycemia, insulin resistance and dyslipidemia leading to atherosclerosis, but also has direct anti-inflammatory effect. Studies have shown that metformin can inhibit inflammatory response, mainly through amp activated protein kinase (AMPK) - dependent or independent inhibition of nuclear transcription factor B (NFB).

7. It can promote hair growth and treat hair loss. The team of Huang Jing, a Chinese scientist at UCLA, has found that metformin, Rapamycin and other drugs can stimulate the hair follicles of mice to enter the growth stage during resting period, and promote hair growth. Relevant research has been published in the famous academic journal cell report. In addition, scientists have observed that metformin is associated with reduced hair loss in Chinese and Indian patients with PCOS. In addition, different studies have shown that metformin also has new findings in some diseases that affect women's health.

8. Reduce the risk of miscarriage and preterm birth in specific pregnant women. A study in the Lancet journal showed that metformin may reduce the risk of abortion and premature delivery in specific pregnant women. According to reports, from the Norwegian University of science and Technology (NTNU), the St.Olavs A nearly 20-year study by hospital scientists found that taking metformin at the end of the third trimester of pregnancy may reduce the risk of late miscarriage and premature delivery.

9. Improve polycystic ovary syndrome polycystic ovary syndrome is a heterogeneous disease characterized by hyperandrogenism, ovarian dysfunction and polycystic ovary morphology. Its pathogenesis is unclear, and patients often have hyperinsulinemia in different degrees. Studies have shown that metformin can reduce insulin resistance, restore ovulation function and improve hyperandrogenemia.

10. Combination therapy, or triple negative breast cancer. The team led by Dr. Marsha rich Rosner of the University of Chicago found that metformin combined with another old drug, heme, can target the treatment of triple negative breast cancer, which seriously threatens women's health. And there is evidence that this treatment strategy may be effective for lung cancer, kidney cancer, uterine cancer, prostate cancer and acute myeloid leukemia. Relevant research was published in the top journal Nature.

11. Cardiovascular protection metformin has cardiovascular protective effect and is the only hypoglycemic drug recommended by diabetes guidelines as having clear evidence of cardiovascular benefits. Studies have shown that long-term metformin treatment is significantly associated with a reduced risk of cardiovascular disease in newly diagnosed type 2 diabetes mellitus patients and those with cardiovascular disease.

12. Improvement of intestinal flora: studies have shown that metformin can restore the proportion of intestinal flora and make it change to the direction of health. It can provide favorable living environment for intestinal beneficial bacteria, thus reducing blood sugar and positively regulating immune system.

13. It is expected to treat some autism. Recently, researchers at McGill University have found that metformin can treat fragile X syndrome in some forms of autism, and this innovative study was published in nature medicine, a sub Journal of nature. At present, autism is one of many medical disorders that scientists believe can be treated with metformin.

14. Reversing pulmonary fibrosis. Researchers from the University of Alabama, Birmingham, USA found that in patients with human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis induced by bleomycin, the activity of AMPK in fibrotic tissues decreased, and the number of myofibroblasts resistant to cell death increased. The use of metformin to activate AMPK in myofibroblasts can re sensitize these cells to apoptosis. In addition, metformin can accelerate the ablation of fibrosis tissue in mice. This study suggests that metformin or other AMPK agonists can be used to reverse fibrosis that has already occurred.

15. Reversing cognitive impairment researchers at the University of Texas at Dallas have developed a mouse model that mimics pain related cognitive impairment. They used the first mock exam to test the efficacy of various drugs. The results showed that metformin 200 mg / kg body weight for 7 days could completely reverse the cognitive impairment caused by pain. Gabapentin, which is used to treat neuralgia and epilepsy, has no such effect. This means that metformin can be used to treat cognitive impairment in patients with neuropathic pain.

16. Inhibition of tumor growth recently, according to singularity.com, scholars from European Cancer Research Institute found that metformin and fasting can cooperate to inhibit tumor growth in mice. Further studies showed that metformin and fasting inhibit tumor growth through pp2a-gsk3 β - Mcl-1 pathway. The study was published on cancer cell.

17. Macular degeneration is the latest finding from Yu-Yen Chen, a general hospital of Taichung Veterans General in Taiwan, China. The incidence rate of age-related macular degeneration (AMD) in type 2 diabetics taking metformin is significantly lower. This suggests that metformin has a protective effect on AMD while controlling diabetes mellitus. Recently, a study was published in Lancet diabetes and endocrinology. The results showed that metformin can improve metabolic health and reduce the serious side effects of glucocorticoid treatment in patients with chronic inflammatory diseases in phase 2 clinical trial. Some experiments suggest that metformin may act through the key metabolic protein AMPK, and the mechanism of action is contrary to that of glucocorticoid, and it has the potential to reverse the side effects caused by the large use of glucocorticoid. The research team led by Robin J.M. Franklin of Cambridge University and his disciple Peter Van wijngaarden published in the top journal Cell stem cell