New effects of metformin discovered

Long-term use of metformin may help to exert anti-cancer effects

According to the WeChat public account Singularity.com, recently, research teams from the University of Texas MD Anderson Cancer Center and other units published important research results in the Journal for ImmunoTherapy of Cancer: long-term use of metformin may be passed Change the tumor immune microenvironment and truly play an anti-cancer effect.

According to Cyberlan’s incomplete analysis, there have been many studies on the benefits of metformin in cancer:

Such as the combination of drugs may be expected to treat triple-negative breast cancer, inhibit tumor growth, protect the stomach, reduce the risk of gastric cancer, extend the survival time of patients with advanced bowel cancer with KRAS mutations, benefit patients with esophageal squamous cell carcinoma, or improve the survival of patients with lung cancer Help reduce the risk of estrogen-positive breast cancer, and combine targeted drugs to extend the survival of patients with advanced lung cancer with EGFR mutations.

Regarding the new role of this discovery, the article points out that previous preclinical studies have shown that in head and neck squamous cell carcinoma (HNSCC), metformin can activate intracellular energy pathways (such as AMPK) and directly inhibit the mitochondrial electron transport chain When combined with conventional radiotherapy and chemotherapy, metformin showed significant anti-tumor efficacy in preclinical models.

The researchers first explored the effect of acute metformin treatment on the immune status of mice. After intraperitoneal injection of metformin into mice for five consecutive days, it was found that in the tumor-draining lymph nodes of tumor-bearing mice, metformin treatment resulted in an increase in the number of CD4+ T cells, while regulatory T cells and myeloid-derived suppressive cells (MDSCs) were immune The number of inhibitory cells is reduced.

Considering that in clinical retrospective studies, patients used metformin for months to years before the cancer was diagnosed.

In order to simulate this clinical situation, the researchers constructed a chronic treatment model. Experiments show that if metformin is used 4 weeks before tumor inoculation, it can significantly reduce the tumor growth rate.

Therefore, these results all indicate that in tumors treated with metformin for a long time, gene expression shows a trend of enhanced immune response, suggesting that metformin may promote anti-tumor immune response, thereby inhibiting tumor growth.

After a large circle of studies on mice, the researchers finally returned to the clinic to verify these findings.

The researchers analyzed 21 HNSCC patients with diabetes, of which 11 patients took metformin at the time of tumor diagnosis and during treatment, and 10 patients used other blood sugar control methods. The researchers found that, compared with diabetic patients who did not take metformin, diabetic patients who took metformin had a higher proportion of tumor-infiltrating CD3+ and CD8+ lymphocytes.

In general, this study found that although metformin can affect the body's immune response, it has no significant inhibitory effect on the tumors that have developed. In contrast, if chronic continuous treatment is started before tumor implantation, significant anti-tumor activity can be produced.

Therefore, the author believes that in future clinical trials, in order to obtain the strongest anti-tumor activity, it is necessary to consider the impact of metformin treatment time. Compared with the short-term "attack guanidine" after diagnosis, giving metformin some time to let it fully exert its effects may be the right answer.

The magic drug metformin, new discoveries continue

As a classic old drug that has been available for more than 60 years, metformin has been highly regarded in the field of hypoglycemia. According to related studies, in addition to its good hypoglycemic function, it can also reduce the risk of heart attack. It also reduces the risk of heart attack in some patients. It is believed to help control weight.

In addition, professional clinical medical institutions are also recognizing the more clinical effects of metformin. Recently, the Guangdong Pharmaceutical Association released the "Extra-instructional Drug List (2021 Edition)" jointly drafted by 57 well-known large-scale tertiary hospitals in the country. In the edition of the catalog, metformin indications have added polycystic ovary syndrome."

Of course, the above-mentioned effects are not the full potential of metformin. According to new research on a global scale, let’s review the potential new effects of metformin. Of course, from the new effects revealed by the preliminary research to the real clinical use, rigorous clinical trials of drugs are needed to confirm.

1. Weight loss

Metformin is a hypoglycemic agent that can lose weight. It can increase insulin sensitivity and reduce fat synthesis. For many type 2 sugar lovers, weight loss itself is a thing that is conducive to stable control of blood sugar.

A study by the United States Diabetes Prevention Program (DPP) research team showed that in an unblinded study period of 7-8 years, patients who received metformin treatment lost an average of 3.1 kg in weight.

2. Anti-aging effect

A few days ago, the U.S. Food and Drug Administration approved a clinical trial of "metformin against aging". The reason why foreign scientists use metformin as an anti-aging drug candidate may be because metformin can increase the number of oxygen molecules released into cells. Above all, this seems to increase the body's fitness and prolong life.

3. Reverse biological age

The official website of the international science and technology journal "Nature" published a blockbuster news. Reports show that a small clinical study in California showed for the first time that it is possible to reverse the human epigenetic clock. In the past year, nine healthy volunteers took a mixture of growth hormone and two diabetes drugs, including metformin. Measured by analyzing the markers on a person's genome, their biological age has dropped by an average of 2.5 years.

4. Anti-smog

Research results show that a team led by Professor Scott Budinger of Northwestern University in the United States confirmed in mice that metformin can prevent inflammation caused by smog, prevent immune cells from releasing a dangerous molecule into the blood, inhibit the formation of arterial thrombosis, and reduce the heart. The risk of vascular disease.

5. Assist in quitting smoking

Researchers at the University of Pennsylvania have found that long-term nicotine use can Lead to the activation of the AMPK signaling pathway, which is inhibited during nicotine withdrawal. Therefore, they concluded that if drugs are used to activate the AMPK signaling pathway, it may alleviate the withdrawal response.

Metformin is an AMPK agonist. When the researchers gave metformin to mice that had nicotine withdrawal, they found that it relieved the mice's withdrawal. Their research shows that metformin can be used to help quit smoking.

6. Anti-inflammatory

Preclinical studies and clinical studies have shown that metformin can not only improve chronic inflammation by improving metabolic parameters such as hyperglycemia, insulin resistance and atherosclerotic dyslipidemia, but also has a direct anti-inflammatory effect.

Studies have pointed out that metformin can inhibit inflammation, 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 the University of California, Los Angeles, discovered that drugs such as metformin and rapamycin can stimulate the hair follicles in the resting phase of mice to enter the growth phase and promote hair growth. Related research has been published in the well-known academic journal Cell Reports.

Moreover, when scientists used metformin to treat patients with polycystic ovary syndrome in China and India, they have also observed that metformin is associated with reduced hair loss.

In addition, different research results show that there are new discoveries about metformin in some diseases that affect women's health.

8. Reduce the risk of miscarriage and premature delivery for certain pregnant women

A study in The Lancet showed that metformin may reduce the risk of miscarriage and preterm delivery in certain pregnant women.

According to reports, scientists from the Norwegian University of Science and Technology (NTNU) and St. Olavs Hospital conducted a nearly 20-year study and found that patients with polycystic ovary syndrome taking metformin at the end of 3 months of pregnancy may reduce post-term miscarriage and miscarriage. Risk of premature birth.

9. Improve polycystic ovary syndrome

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

10. Combination medication may treat triple-negative breast cancer

The team led by Dr. Marsha rich rosner of the University of Chicago found that the combination of metformin and another old drug, heme (panhematin), can target the treatment of triple-negative breast cancer that seriously threatens women’s health.

And there is evidence that this treatment strategy may be effective for a variety of cancers such as lung cancer, kidney cancer, uterine cancer, prostate cancer, and acute myeloid leukemia. Related research has been published in the top journal Nature.

11. Cardiovascular protection

Metformin has cardiovascular protective effects and is currently the only hypoglycemic drug recommended by the diabetes guidelines as having clear evidence of cardiovascular benefit. Studies have shown that long-term treatment of metformin is significantly related to the decreased risk of cardiovascular disease in newly diagnosed type 2 diabetic patients and type 2 diabetic patients who have already developed cardiovascular disease.

12. Improve intestinal flora

Studies have shown that metformin can restore the proportion of intestinal flora and make it change in a direction that is conducive to health. It provides an advantageous living environment for the beneficial bacteria in the intestines, thereby lowering blood sugar and positively regulating the immune system.

13. It is expected to treat some autism

Recently, researchers at McGill University discovered that metformin can treat some forms of Fragile X syndrome with autism, and this innovative study was published in the journal NatureMedicine, a subsidiary of Nature. At present, autism is one of many medical conditions that scientists believe can be treated with metformin.

14. Reverse pulmonary fibrosis

Researchers at the University of Alabama at Birmingham found that in human patients with idiopathic pulmonary fibrosis and mouse pulmonary fibrosis models induced by bleomycin, the activity of AMPK in fibrotic tissues is reduced, and the tissues resist cells. The apoptotic myofibroblasts increased.

Using metformin to activate AMPK in myofibroblasts can re-sensitize these cells to apoptosis. Moreover, in the mouse model, metformin can accelerate the ablation of the already produced fibrotic tissue. This study shows 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 created a mouse model that mimics pain-related cognitive impairment. They used this model to test the efficacy of multiple drugs.

Experimental results show that treatment of mice with 200 mg/kg body weight of metformin for 7 days can completely reverse the cognitive impairment caused by pain.

Gabapentin, which treats neuralgia and epilepsy, has no such effect. This means that metformin can be used as an old drug to treat cognitive impairment in patients with neuralgia.

16. Inhibit tumor growth

A few days ago, according to Singularity.com, scholars from the European Institute of Oncology discovered that metformin and fasting can work synergistically to inhibit the growth of tumors in mice.

Through further research, it was found that metformin and fasting inhibit tumor growth through the PP2A-GSK3β-MCL-1 pathway. The research was published on Cancer Cell.

17, can prevent macular degeneration

Dr. Yu-Yen Chen from Taichung Veterans General Hospital in Taiwan, China recently discovered that the incidence of age-related macular degeneration (AMD) in patients with type 2 diabetes taking metformin is significantly lower. This shows that while controlling diabetes, the anti-inflammatory and antioxidant functions of metformin have a protective effect on AMD.

18. May reduce adverse effects of glucocorticoids

Recently, "The Lancet-Diabetes and Endocrinology" published a study-the results of the study showed that in a phase 2 clinical trial, metformin used in patients with chronic inflammatory diseases can improve metabolic health and reduce glucocorticoid treatment Serious side effects.

Experiments have suggested that metformin may act through the key metabolic protein AMPK, and the mechanism of action is exactly the opposite of glucocorticoids, and has the potential to reverse the side effects caused by the massive use of glucocorticoids.

19. Hope to treat multiple sclerosis

Previously, a research team led by Robin JM Franklin of the University of Cambridge and his disciple Peter van Wijngaarden published an article in the top journal "Cell Stem Cells" that they found a special type of aging neural stem cells that can recover after treatment with metformin. In response to differentiation-promoting signals, it reappears youthful vitality and further promotes the regeneration of nerve myelin.

This discovery means that metformin is expected to be used in the treatment of irreversible neurodegeneration-related diseases, such as multiple sclerosis.

20. It is expected to improve the risk of kidney failure and death from kidney disease

WuXi AppTec's content team Medical New Vision released news that a study of 10,000 people showed that metformin may improve the risk of kidney failure and death from kidney disease.

A study published in the American Diabetes Association (ADA) journal "Diabetes Care" (Diabetes Care) showed that the medication and survival analysis of more than 10,000 people showed that type 2 diabetes patients with chronic kidney disease (CKD) take Metformin is associated with a reduction in the risk of death and end-stage renal disease (ESRD), and does not increase the risk of lactic acidosis.

Although there are so many exciting discoveries about metformin, the medicine is three points poisonous. Don't buy the medicine yourself and use it under the guidance of a doctor.

21. It can protect the stomach and reduce the risk of stomach cancer

Recently, the official website of "Cell Stem Cell", a subsidiary of the world's top scientific journal "CELL", updated the latest research on metformin: Metformin can regulate the metabolism of stem cells in the stomach and promote them to differentiate into gastric parietal cells that produce gastric acid.

Studies have shown that the AMPK metabolic pathway promotes the generation of acid-secreting parietal cells by stem cells. Metformin slows down the proliferation of progenitor cells by activating AMPK and KLF4, and can also induce parietal cell maturation by activating AMPK and PGC1a. This is why metformin increases acid secretion and Lowering people's risk of gastric cancer provides potential hints.

In addition, a 2018 study showed that the use of metformin reduced the risk of gastric cancer by 51% in diabetic patients with Helicobacter pylori eradicated in a sustained and dose-response manner.

22. Take preoperatively to reduce the mortality of patients

According to WuXi AppTec's account medicine new perspective news, a recent study published in the Journal of the American Medical Association-Surgery found that the classic hypoglycemic drug metformin has another benefit in addition to blood sugar control: taking metformin before surgery may be It is related to the postoperative mortality of diabetic patients and the reduced risk of readmission.

23. Extend the survival time of patients with advanced bowel cancer with KRAS mutations

According to Singularity.com, a team of Chinese scientists, Gao Guoquan and his team at Zhongshan Medical College, Sun Yat-Sen University, recently published important research results in the well-known journal PNAS.

They analyzed the treatment data of thousands of patients with advanced bowel cancer and found that among patients with advanced bowel cancer with KRAS mutations, compared with other types of hypoglycemic drugs, the overall survival time of intestinal cancer patients taking metformin was 37.8 longer than that of other types of hypoglycemic drugs. Month, median none

The progression survival time (mPFS) was extended by 8.1 months.

24. Preventing cancer and stroke trends

According to news from the new medical perspective, the 80th Scientific Meeting of the American Diabetes Association (2020 ADA Annual Meeting) announced the latest data from the Diabetes Prevention Program Outcome Study (DPPOS)-Metformin has continued to reduce the risk of diabetes for 22 years, showing the trend of preventing cancer and stroke.

25, repair brain damage

In the journal Nature Medicine, researchers from the Institute of Medical Sciences of the University of Toronto in Canada and the Toronto Children’s Hospital published the results of the test: For children with brain tumors who have received craniocerebral radiotherapy, metformin is more pronounced than placebo Improved their working memory and statement memory function, repaired white matter damage.

26. Benefit patients with esophageal squamous cell carcinoma

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.

The paper shows that the hypoglycemic drug metformin may benefit patients with esophageal squamous cell carcinoma by improving the immune microenvironment (TIME) in tumor lesions.

27, or reduce the risk of dementia

Recently, the journal Diabetes Diagnosis and Treatment of the American Diabetes Association published a study from Australia-the above study found that patients with type 2 diabetes who took metformin had slower cognitive decline and a lower risk of dementia.

The first author of the study, Professor Katherine Samaras, an endocrinologist at St. Vincent’s Hospital in Sydney, said, “Metformin is safe and widely used. These data indicate its new potential. For patients with type 2 diabetes, metformin may bring cognition beyond sugar control. Health benefits. More broadly, for people at high risk of dementia and their families, this may change their lives."

28. Work in conjunction with androgen blockade therapy

Studies have shown that combined therapy with androgen blockade (ADT) and metformin may be a feasible treatment for prostate cancer.

According to the article "Mol Cancer Ther: Metformin can synthesize lethal metabolism to target androgen-deficient prostate cancer cells" recently published by the WeChat public account "MedSci Metz", researchers have recently investigated the response of prostate cancer (PC) cells to androgens Blocking therapy treats the mechanism of aging, and it is determined whether metformin and androgen blockade therapy have a synergistic effect in prostate cancer in vitro and in vivo.

The researchers pointed out that the combination of androgen blockade therapy and metformin may be a viable treatment method that can eliminate PC cells that persist after androgen blockade therapy.

29. Metformin may improve the survival rate of lung cancer patients

According to news from the new medical perspective, a recent study published in the British Journal of Cancer showed that in all lung cancer patients, taking metformin is associated with improved survival, especially in local (TNM stage II- Stage III) in patients with lung squamous cell carcinoma.

The article pointed out that among lung cancer patients, diabetes is one of the common underlying chronic diseases. A number of studies have observed that in lung cancer patients with diabetes, taking metformin has a positive effect on survival. However, clinical trials in patients with non-diabetic lung cancer have not reached a consistent conclusion.

30. Or significantly reduce COVID-19 mortality in women with type 2 diabetes or obesity

Recently, according to Bio Valley reports, a study published in Lancet Healthy Longev recently showed that metformin can significantly reduce the mortality of COVID-19 in women with type 2 diabetes or obesity.

31. Help reduce the risk of estrogen-positive breast cancer

Recently, an article in Biological Valley pointed out that two research reports published in the international journal "Annals of Oncology" stated that scientists from the National Institutes of Health and other institutions have discovered through research that metformin may affect type 2 The risk of breast cancer in women with diabetes.

In a study of 44,541 women, the researchers found that, in general, there did not seem to be an association between type 2 diabetes and the individual's risk of breast cancer. This may be because most of the type 2 diabetes patients in the study are taking metformin, and metformin is a drug for the treatment of type 2 diabetes, which may help reduce the risk of estrogen-positive (ER-positive) breast cancer.

32. Combining targeted drugs to extend the survival of patients with advanced lung cancer with EGFR mutations

According to a report from "Yi Shi Xiang", recently, the first clinical trial confirmed that metformin combined with targeted drugs as first-line therapy can extend the survival of patients with advanced lung cancer with EGFR mutations by 14 months.

33. Improve inflammation and fatty liver symptoms caused by artificial sugar substitutes

In March 2021, researcher Zhang Limin from the Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences led the team and published the title: "Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver" in the famous journal "mSystems" in the field of microbiology. The research paper of "Disease in Mice" analyzed how saccharin and sucralose, two common artificial sugar substitutes, caused non-alcoholic fatty liver by changing the intestinal microbiota.

The results show that both metformin and FOS can significantly increase the Akkermania population in the intestines of mice ingesting sugar substitutes. More importantly, they can also significantly improve inflammation and fatty liver symptoms caused by artificial sugar substitutes.

The study also raised the possibility of using metformin and Fructooligosaccharides to treat liver disease caused by long-term intake of artificial sugar substitutes.

34. As an adjuvant therapy for the treatment of AIDS

Recently, according to "Bioworld" report, on March 25, 2021, researchers from the University of North Carolina School of Medicine published a titled "Multi-omics analyses reveal that HIV-1 alters" in the Nature sub-Journal "Nature Immunology". CD4+ T cell immunometabolism to fuel virus replication" research paper.

The study found that metformin can act on mitochondrial respiratory chain complex I, inhibit the oxidative phosphorylation (OXPHOS) pathway, and thereby inhibit the replication of human CD4+ T cells and HIV-1 virus in humanized mouse models.

This finding suggests that metformin, like other drugs that reduce T cell metabolism, can be used as an adjuvant therapy for the treatment of AIDS.

35. Reduce chronic inflammation in HIV-infected people

A study found that metformin can help HIV-infected people who are receiving anti-ART treatment to reduce chronic inflammation. Petronela Ancuta, the corresponding author of the study and professor of immunology at the University of Montreal, said: "Previous studies have shown that inhibiting mTOR with drugs can significantly inhibit the replication of HIV in the cells of virus-infected patients, thereby reducing chronic inflammation."

The researchers used metformin to treat 22 non-diabetic HIV-infected patients receiving antiretroviral therapy and found that the patients tolerated the drug extremely well. Moreover, the researchers observed the beneficial biological effects of metformin in colon biopsy. It was found that the activation of mTOR in CD4 T cells present in the colon was reduced, and certain plasma markers of inflammation and intestinal injury were reduced. Therefore, metformin has intestinal and systemic effects.

36. Relieve premature preeclampsia

A study published at the 2021 pregnancy conference of the Society of Maternal and Child Medicine showed that among pregnant women with pre-eclampsia, metformin prolonged pregnancy by nearly one week and was also related to the shortened hospitalization time of newborns. Pre-eclampsia refers to symptoms such as high blood pressure, proteinuria, headache, vertigo, nausea, vomiting, and upper abdominal discomfort during pregnancy. In women with normal blood pressure, pre-eclampsia usually starts after 20 weeks of pregnancy.

Professor Cathy Cluver of Stellenbosch University in Cape Town, South Africa said: “Metformin may be a drug for the treatment of pre-eclampsia of premature birth. We plan to carry out a larger study, hoping to confirm these findings, and provide support for prolonging pregnancy and improving neonatal outcomes. plan."

37. Improve the symptoms of tuberous sclerosis

A study published in the "Lancet" sub-Journal EBio Medicine found that metformin can successfully reduce symptoms related to tuberous sclerosis (TSC), including reducing the frequency of seizures and the size of brain tumors.

The research team found that people who took metformin had a 21% reduction in brain tumor volume within a year, while those who took a placebo increased their tumor volume by 3%. The seizure frequency of patients taking metformin decreased by 44%, while the placebo group only decreased by 3%.

Finbar O'Callaghan, Professor of Pediatric Neuroscience at University College London, said: "We have found that metformin is more effective in treating young TSC patients. Patients with seizures several times a day or multiple times a week have no seizures after 12 months of treatment, while other patients The number of seizures is also less than before. Next, further large-scale trials will be carried out in TSC patients to determine the optimal dose and effect of metformin."

38. Application of metformin in radiotherapy of malignant tumors

According to medical reports, metformin is still actively used in radiotherapy for malignant tumors.

A paper published in "Chinese Cancer Clinic", "The application of metformin in malignant tumor radiotherapy" pointed out that metformin can inhibit DNA damage and repair, regulate cell cycle distribution, and induce the generation of reactive oxygen species in malignant tumor radiotherapy. Change the metabolism of tumor cells and enhance the sensitivity of tumor cells to radiation. Metformin can be used as an effective radiosensitizer and has important potential application value in the treatment of malignant tumors.

39. Metformin may relieve portal hypertension

According to Singularity.com, the latest clinical studies have preliminarily confirmed that metformin can reduce portal pressure in patients with liver cirrhosis and is expected to alleviate portal hypertension.

Although metformin has multiple possible new effects, its main business is still hypoglycemic. Non-indications may lower blood sugar and threaten their health. It must not be used without authorization.