Introduction: Recently, I have seen metformin referred to as a “miracle drug” on the Internet, and it has been used in clinical studies in the UK to “prolong life”. Metformin has been on fire for a while, and has also greatly attracted the attention of patients with polycystic ovary syndrome (hereinafter referred to as PCOS). Sisters diagnosed with PCOS often have this doubt: I went to the doctor at first because of “irregular menstruation” and “infertility”, and the doctor said I had “polycystic ovary syndrome”. The doctor said I had “polycystic ovary syndrome” and made me do a “sugar water test” and said I had “abnormal glucose tolerance (IGT)”, “insulin resistance (IR)”, etc. I was told to lose weight and gradually increase the dosage of “Metformin” …… isn’t metformin a “glucose-lowering drug”? But I don’t have diabetes, why should I take this and how should I take it? What does this have to do with the “miracle drug” that the internet is talking about? There is a lot of information, can’t hold it! PCOS patients are often associated with metabolic abnormalities First of all, it must be clear that polycystic ovary syndrome (hereinafter referred to as PCOS) is a reproductive dysfunction and metabolic abnormalities coexist. Metabolic abnormalities include insulin resistance, abnormal glucose metabolism, hyperlipidemia, etc. If not intervened, it may later develop into diabetes, obesity, metabolic syndrome, cardiovascular disease, etc. For women who are trying to get pregnant, poorly controlled metabolic problems can also aggravate reproductive dysfunction, including ovulation disorders, and become one of the many factors in infertility, difficulty in embryo implantation, higher miscarriage rates, and gestational diabetes. What is insulin resistance? Under normal circumstances, when we eat, glucose in the blood will rise, and insulin in the body will be secreted more to promote the use of glucose by cells, so that blood glucose will not soar. The body desperately wants to lower blood sugar and has to use more insulin, resulting in high insulin in the blood, which makes it easy to deposit fat and make people fat and prone to metabolic diseases. High insulin also aggravates the hyperandrogenemia of PCOS, which leads to irregular menstruation, non-ovulation and infertility. Obese patients with polycystic ovary syndrome are more likely to have combined insulin resistance, but thin people are not necessarily immune, as studies have found that 30% of non-obese PCOS patients still have insulin resistance. How do you assess for metabolic problems in PCOS? The most intuitive is to look at the fat first, specifically through BMI, waist circumference to assess the obesity of PCOS is usually manifested as centripetal obesity, even if the limbs are not fat, but the waist is thicker (waist circumference greater than 80cm), then we should suspect the existence of insulin resistance. The rest of the indicators include black acanthosis (dark and rough skin folds in the neck and armpits), blood lipids, blood pressure, etc., and oral glucose tolerance test (OGTT) + insulin release test, which is the previously mentioned “sugar water test,” in which blood is drawn at a fixed time before and after the oral dose of sugar water to test glucose and insulin levels respectively. The OGTT tests the body’s ability to regulate blood glucose, and abnormal results can be manifested as impaired fasting glucose IFG (high fasting glucose), or impaired glucose tolerance IGT (high blood glucose after taking sugar water), or diabetes (elevated blood glucose more severe than the first two). The presence of insulin resistance can be assessed by blood glucose and blood insulin levels. What should I do if I have “insulin resistance”? Metformin is an insulin sensitizer, as the name implies, which improves the sensitivity of tissue cells to insulin, allowing the cells to use glucose quickly, and also inhibits the liver from producing glucose, so that blood sugar comes down and insulin does not have to be secreted as much, and hyperglycemia and hyperinsulinemia are improved. This may be beneficial for weight loss, regulation of menstruation, ovulation, and reducing the risk of long term metabolic disease. Who should use it? Our Expert Consensus on the Diagnosis and Treatment of Polycystic Ovarian Syndrome (2008) recommends metformin for patients with PCOS who are obese or insulin resistant. 2010 European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) consensus on the treatment of PCOS recommends metformin for patients with PCOS with impaired glucose tolerance. 2013 American The 2013 American Society for Endocrinology guidelines for the management of polycystic ovary syndrome recommend the addition of metformin for patients with PCOS who have impaired glucose tolerance or metabolic syndrome in combination and for whom lifestyle modification has not been effective. How does metformin work? It is important to use enough to achieve efficacy. Metformin may bring about gastrointestinal reactions, that is, nausea, vomiting, bloating, diarrhea, indigestion, and abdominal discomfort. To reduce adverse reactions and enable patients to adhere to the full dose, start with a small dose and gradually increase the dose and take it with meals. Patients are usually told to take each dose at the same time as a meal and to increase the dose gradually. Week 1: 1 tablet (500 mg) once a day, e.g., one tablet with dinner every day; Week 2: if there is no GI reaction, increase the dose: 1 tablet twice a day with two meals; Week 3: if there is no discomfort, increase the dose: 1 tablet three times a day, i.e., 1 tablet with each of three meals, and maintain the dose thereafter. If you find the adverse effects intolerable after increasing the dose, you can drop to the previous lower dose, tolerate it and then try to increase the dose. Don’t worry too much, many people have no adverse reactions from the beginning to the end, and even if they do, most of the gastrointestinal discomfort caused by metformin occurs early in the dosing period (the first 10 weeks), and most people’s discomfort will gradually disappear as the duration of treatment increases. Use in special populations Can I use metformin after pregnancy? For mothers-to-be, if blood sugar is not well controlled during pregnancy, the incidence of embryonic malformations, miscarriage, and giant babies increases when the baby is in a hyperglycemic environment while developing inside the mother. Huge babies will be more prone to obesity, diabetes, hypertension, increased risk of cardiovascular disease, and possibly even intellectual defects and hyperactivity in childhood and adulthood. Therefore, it is best to have a blood glucose test before pregnancy, intervene if necessary, and become pregnant after satisfactory indicators. Blood glucose control during pregnancy is also important, so is it still possible to use metformin while pregnant? A number of studies in patients with gestational diabetes have confirmed the safety and efficacy of metformin use in early pregnancy. Studies in patients with PCOS have also shown that the use of metformin in early pregnancy does not increase the risk of fetal malformations and may reduce the incidence of miscarriage, gestational diabetes, and macrosomia. In the FDA’s classification of medications for pregnancy, metformin is a class B drug, which means it is relatively safe, but the Chinese drug regulatory authority has not approved the use of metformin in women during pregnancy, so many doctors would recommend discontinuing the drug after pregnancy is detected. Whether to use the drug or not, it is best to discuss with your doctor to weigh the pros and cons and develop a plan that suits you. For people with impaired liver or kidney function For people with impaired liver function: It is generally recommended to avoid the use of serum aminotransferase when it exceeds 3 times the upper limit of normal, and to monitor liver function closely when using it for mildly high aminotransferase. For people with impaired renal function: adjust the dosage by estimating the glomerular filtration rate (eGFR): no dosage reduction is required for eGFR ≥ 60, dosage reduction is required between 45-60, and discontinuation is required for less than 45. The reason for this is the concern that diseases of the liver and kidneys themselves affect the normal lactate clearance and lead to lactic acidosis, but this is very rare. Metformin itself is not hepatorenal toxic and is not a concern for normal people. People who need imaging do not need to stop using it before imaging if their kidney function is normal, and stop using it for 2-3 days after imaging, and can continue using it if their kidney function is normal on recheck. Long-term use of metformin for people with vitamin B12 deficiency can cause a decrease in vitamin B12 levels and should not be used by people with uncorrected vitamin B12 deficiency. For people who are not vitamin B12 deficient, appropriate vitamin B12 supplementation is recommended for long-term users. Besides improving insulin resistance, metformin has many other effects? Studies have shown additional benefits of metformin including: cardiovascular protective effects, improvement of blood lipids, improvement of fatty liver (non-alcoholic), and tumor suppressive effects. Metformin is so powerful and cheap, no wonder some people call metformin “miracle drug”, but it does not mean that with it you can “lazy”, you know, “keep your mouth shut, open your legs “The lifestyle modification is also an important part of the treatment of metabolic abnormalities in PCOS. Diet plus exercise + taking medication as prescribed by the doctor is the only way to good health.