The latest study found that metformin may help reduce the risk of estrogen-positive breast cancer

1. New discovery of metformin

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 diabetic patients in the study are taking metformin, which is a drug for the treatment of type 2 diabetes, and its effects may help reduce the risk of estrogen-positive (ER-positive) breast cancer.

ER-positive breast cancer (that is, cancer cells with estrogen receptors on the surface) account for about 80% of breast cancer patients diagnosed in the United States, and these associations found in the study indicate that there is a relationship between type 2 diabetes and breast cancer The association differs by breast cancer subtype and is affected by the use of metformin to treat diabetes.

Researcher Professor Dale Sandler said that for 15 years or more, patients with type 2 diabetes seem to be associated with a 39% reduction in the risk of ER-positive breast cancer. We think this is most likely due to their long-term use of metformin.

The results of the study show that, compared with non-diabetic patients, type 2 diabetes patients who have taken metformin for 10 years or more have a 38% lower risk of ER-positive breast cancer.

In conclusion, relevant research results indicate that patients with type 2 diabetes may increase their risk of breast cancer, but the intake of metformin may effectively protect their body against the occurrence of ER-positive breast cancer.

Finally, the researchers concluded that more in-depth research by scientists is needed in the later stage to unravel the in-depth association between type 2 diabetes, therapy and breast cancer risk. It is worth noting that as early as the 2018 edition of "Metformin Clinical Application Expert Consensus" mentioned, a number of studies have shown that metformin can activate the AMPK pathway, and the activation of the AMPK pathway can inhibit the occurrence and development of tumors in addition to affecting metabolism. Multiple meta-analysis results show that metformin treatment is associated with a reduction in the risk of lung cancer, prostate cancer, rectal cancer, breast cancer and other cancers.

2. The possible multiple effects of metformin

In recent years, the multiple possible effects of metformin have aroused widespread concern. According to the 2018 edition of "Expert Consensus on the Clinical Application of Metformin", the possible effects of metformin are:

1) Cardiovascular protection Metformin has a direct or indirect cardiovascular protection effect by effectively improving the insulin resistance of diabetic and non-diabetic patients and reducing the basal and post-load insulin levels. The UKPDS study showed that obese type 2 diabetes mellitus (T2DM) patients who used metformin had a relative reduction of 35% in the risk of all-cause death and a 39% reduction in the risk of myocardial infarction. The UKPDS 10-year follow-up study showed that the benefits of metformin treatment for macrovascular complications and the risk of death have a continuation effect, and its effect in reducing death and myocardial infarction is significantly better than that of sulfonylureas and insulin.

2) The effect of improving blood lipids Metformin can improve fat synthesis and metabolism. A number of studies have shown that metformin can significantly reduce plasma TG, LDL-C and TC levels in patients with T2DM, but does not change HDL-C significantly.

3) Improve the effect of non-alcoholic fatty liver disease. Unless there is significant liver damage (for example, serum transaminase greater than 3 times the upper limit of normal), liver insufficiency, or decompensated liver cirrhosis, patients with non-alcoholic fatty liver can safely use metformin . There are 14 clinical studies evaluating the improvement of metformin on liver histology, serum enzymes and insulin resistance in patients with non-alcoholic fatty liver. All studies showed significant improvement in insulin resistance index, 13 studies showed that serum enzymology (alanine aminotransferase, aspartate aminotransferase) was significantly decreased, and 5 studies showed that metformin significantly improved liver inflammation, steatosis and fibrosis.

4) The effect of treating polycystic ovary syndrome Polycystic ovary syndrome (PCOS) is a heterogeneous disease characterized by hyperandrogenemia, ovarian dysfunction, and polycystic ovary morphology. Its pathogenesis is unclear, and patients often There are varying degrees of hyperinsulinemia. Evidence-based medical evidence shows that metformin can lower plasma insulin levels, lower androgen levels, increase estradiol levels, improve hirsutism in patients with PCOS, make menstruation regular, and induce ovulation.

5) Anti-tumor effect Diabetes may be a risk factor for a variety of tumors, such as breast cancer, pancreatic cancer, colorectal cancer, and endometrial cancer. A number of studies have shown that metformin can activate the AMPK pathway, and the activation of the AMPK pathway can inhibit the occurrence and development of tumors in addition to affecting metabolism. Multiple meta-analysis results show that metformin treatment is associated with a reduction in the risk of lung cancer, prostate cancer, rectal cancer, breast cancer and other cancers.

3. More useful discoveries

In addition, according to the review of the Center for Drug Evaluation, other anti-diabetic effects reported in the relevant literature:

1) Change the intestinal flora. Intravenous metformin is much less effective than oral hypoglycemic. Recent studies have found that metformin can trigger beneficial changes in the gut microbes of patients with type 2 diabetes, thereby enhancing the ability of bacteria to produce special types of short-chain fatty acids, such as butyric acid and propionic acid. These short-chain fatty acids can effectively lower blood sugar in a variety of ways Level. Animal experiments have shown that the simultaneous administration of metformin and broad-spectrum antibiotics can affect the hypoglycemic effect of metformin.

2) Reduce the risk of Parkinson's disease in patients with type 2 diabetes. Metformin can activate the atypical protein kinase C (aPKC)-CBP pathway in downstream neural stem cells through the AMPK signaling pathway, promote the growth of new neurons, and have a repairing effect on nervous system damage. A retrospective cohort study showed that the risk of Parkinson's in patients with type 2 diabetes was 2.2 times that of non-diabetic patients, and the risk of patients treated with sulfonylureas alone was increased by 57%. The risk of sulfonylureas in combination with metformin did not increase.

3) Reversing left ventricular hypertrophy in non-diabetic patients A randomized controlled trial confirmed that metformin can reverse left ventricular hypertrophy in non-diabetic patients. This may be related to metformin reducing the weight of patients, improving the function of vascular endothelial cells, inhibiting ventricular remodeling, and delaying cardiomyocyte apoptosis. Previous studies have proven that obese type 2 diabetes patients who use metformin have a relative reduction of 35% in the risk of all-cause death and a 39% reduction in the risk of myocardial infarction. Combined use of metformin and insulin can increase the hypoglycemic effect of insulin and reduce the amount of insulin. Compared with insulin alone, it can reduce the risk of macrovascular events.

4) Prevention of age-related macular degeneration. Age-related macular degeneration is a degenerative disease. As age increases, retinal tissue degenerates and becomes thinner, causing a decline in macular function. Macular degeneration is one of the most difficult to treat eye diseases recognized by the international ophthalmology community. At present, there are not many effective treatment methods for macular degeneration. A new study from Taiwan, China found that the incidence of age-related macular degeneration in patients with type 2 diabetes taking metformin is significantly lower, which may be related to the anti-inflammatory and antioxidant functions of metformin.

5) Reversal of pulmonary fibrosis. Researchers at the University of Alabama at Birmingham found that in human patients with idiopathic pulmonary fibrosis and in mice with bleomycin-induced pulmonary fibrosis, the activity of AMPK in fibrotic tissue is reduced , And there are more myofibroblasts in the tissues that resist apoptosis. 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.

6) Reduce the risk of thrombosis caused by smog. After the fine particulate matter (PM2.5) in the air enters the human body, it can cause the alveolar macrophages to release the inflammatory factor interleukin-6 (IL-6). Animal experiments and human studies have proved IL-6 It induces the expression of a variety of coagulation factors in the liver, and has a tendency to increase arterial thrombosis. Animal studies have shown that metformin can prevent inflammation caused by smog, prevent immune cells from releasing a dangerous molecule into the blood, and inhibit the formation of arterial thrombosis, thereby reducing the risk of cardiovascular disease.

7) Reducing the side effects of glucocorticoid therapy A recent study explored the possibility of using metformin in conjunction with glucocorticoid therapy to reverse the adverse effects of glucocorticoids. This randomized, double-blind, placebo-controlled Phase 2 clinical trial enrolled 53 patients without diabetes and receiving continuous prednisone treatment in four hospitals in the United Kingdom. Among them, 26 received metformin treatment and 27 received placebo treatment, with gradual doses Increasingly, lasting 12 weeks in total. The results of the study showed that the subcutaneous fat of the trunk in the metformin group was reduced, carbohydrates, lipids, liver and bone metabolism indexes were improved, inflammatory indexes and clinical indexes of disease activity were all improved.

8) Reduce postoperative mortality and risk of readmission. AMPK activators such as metformin can inhibit the expression of inflammation-related genes and reduce tissue inflammatory damage through complex mechanisms. Studies have found that metformin can significantly reduce the damage of alveoli and respiratory bronchioles, reduce the infiltration of neutrophils and macrophages, and reduce pulmonary edema. A recent study published in the Journal of the American Medical Association Surgery found that people who took metformin before surgery had a 28% reduction in relative risk of death within 90 days after surgery, and a 16% reduction in relative risk of re-admission within 30 days and within 90 days. 14%.

9) Promote hair growth and treat hair loss HuangJing's team, a Chinese scientist at the University of California, Los Angeles, found that metformin, rapamycin and other drugs 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 famous academic journal " Cell Report. 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.

10) Assisting in smoking cessation Researchers from the University of Pennsylvania have found that long-term nicotine use can lead to the activation of AMPK signaling pathway, and AMPK signaling pathway will be inhibited when 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.

11) Reversal of biological age The official website of the international scientific journal "Nature" published a blockbuster news. A small clinical study in California, USA, 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. It must be noted that although the research on metformin has always been discovering new effects, from early research to the expansion of the final indications, a series of processes and more experimental confirmation are needed. Metformin is used as a hypoglycemic prescription drug. , It is not an indication for the crowd, please do not use it indiscriminately