Among the many drugs used in the treatment of diabetes, metformin is the most widely used single drug with the strongest evidence of efficacy and the highest health economic benefit. As a classic drug that has been around for decades, metformin has gone through a rough patch, from being on the verge of being withdrawn from the market to becoming a core drug in the fight against type 2 diabetes (hereafter referred to as diabetes). More and more evidence-based medical evidence has established metformin as the king in the field of diabetes treatment. In the face of such an important drug, every diabetic patient needs to be fully informed, so let’s learn together. A. Metformin throughout the timeline of diabetes treatment Prevention of diabetes Stepping into middle and old age, being overweight or obese, having a diabetic in the immediate family, long-term lack of physical activity …… These are all risk factors that predispose to diabetes. For people at high risk of diabetes, they should first adjust their lifestyles and develop good eating and exercise habits. If the effect is not obvious and blood glucose still rises gradually and reaches “pre-diabetic” status, metformin can be used to delay and prevent the progression of diabetes. Starting treatment for diabetes Metformin has a superlative position among glucose-lowering drugs and is the drug of choice for diabetic patients. It is now believed that once diabetes is diagnosed, metformin should be the first choice of treatment unless there are contraindications to its use or drug intolerance. Long-term treatment of diabetes mellitus In the relevant guidelines and consensus at home and abroad, metformin is set as the first choice and full course drug for diabetes mellitus treatment. This means that if metformin alone does not work well, it is not recommended to change the drug, but to add other hypoglycemic drugs to continue treatment. In other words, metformin is used throughout the treatment of diabetes mellitus. Second, the correct use of metformin Dose The efficacy of metformin shows a dose-dependent effect, and the current clinical use of dose is generally low. Generally speaking, the recommended optimal effective dose is 2000 mg per day, with a maximum of 2550 mg. To prevent the occurrence of side effects such as gastrointestinal discomfort, it is recommended to start with a small dose and gradually increase to an appropriate dose. Dosage form You may notice that the same “metformin” looks very different. The reason for this is that there are various dosage forms of the drug, such as regular, enteric, and extended-release formulations. Compared to regular tablets that disintegrate rapidly in the stomach, enteric soluble formulations begin to dissolve only after entering the intestinal tract, and extended-release formulations dissolve slowly and continuously in the gastrointestinal tract. Although there is no significant difference in efficacy between the different dosage forms, the extended release and enteric soluble formulations can significantly reduce the gastrointestinal side effects of the drug. Third, metformin has a wide range of action Diabetes Metformin can inhibit hepatic synthesis of output glucose, improve insulin sensitivity, reduce intestinal glucose absorption, thus exerting a hypoglycemic effect. Not only can it work alone, metformin can also be used in combination with various other glucose-lowering drugs to play a synergistic role in sugar control. Even for patients with “type 1 diabetes” who must use insulin, metformin can be used to reduce insulin dosage and better maintain body weight and blood lipid levels. Overweight and obesity Metformin can help reduce weight by suppressing appetite, improving hyperinsulinemia, and increasing leptin sensitivity, especially in patients with combined overweight and obesity with diabetes. However, metformin is not currently recommended for the treatment of simple obesity with normal blood glucose. Lipid metabolism disorders Metformin can reduce plasma triglyceride, total cholesterol, LDL cholesterol levels and reduce liver steatosis in diabetic patients, and has an improvement effect on dyslipidemia and fatty liver. Polycystic ovary syndrome (PCOS) Metformin can improve the symptoms of hirsutism, promote regular menstruation and induce ovulation in PCOS patients. Foreign guidelines have listed metformin as the first-line drug for monotherapy or combination therapy in adolescent PCOS patients. Cardiovascular protection Patients using metformin have a significantly lower risk of cardiovascular events compared to other hypoglycemic agents. This may be attributed to the all-round effect of metformin in improving glucolipid metabolism, controlling body weight, and reducing insulin resistance, which comprehensively reduces the risk factors for cardiovascular disease. IV. Metformin in special states Elderly There is no age restriction on the use of metformin, but for patients over 65 years of age, monitoring of renal function at 3-6 month intervals is recommended. Children Metformin is not recommended for use in children under 10 years of age for the time being due to lack of sufficient evidence to support it. Pregnant women Metformin belongs to class B drugs in the pregnancy drug use classification, which does not increase the risk of fetal malformation and neonatal complications, and has advantages in controlling maternal weight and improving insulin resistance. V. China’s drug regulatory authorities have not approved the application of metformin to pregnant women with gestational diabetes mellitus Hepatic insufficiency Metformin is not metabolized by the liver and does not have hepatotoxicity. It only needs to be avoided when serum aminotransferase exceeds 3 times the upper limit of normal or when there is severe hepatic insufficiency. Liver function should be closely monitored for mildly elevated transaminases. Renal insufficiency Metformin itself has no effect on renal function, and the clinical practice of discontinuing metformin when proteinuria is seen is unfounded. Dose adjustment by estimation of glomerular filtration rate (eGFR) is recommended: no dose reduction is required for eGFR ≥ 60, dose reduction is required between 45 and 60, and is contraindicated for less than 45. Contrast examinations To prevent short-term renal overload and avoid metformin accumulation, suspension of metformin prior to contrast administration was previously required. The new view is that stopping metformin 2 days before imaging is only applicable to patients with abnormal renal function; for diabetic patients with normal renal function, it is not necessary to stop the drug before imaging, but it is recommended to stop the drug for 2-3 days after imaging, and then continue the drug after the renal function is normal on review. VI. Contraindications to the use of metformin Any drug has indications and contraindications, and metformin cannot be used in the following cases: moderate to severe renal insufficiency (eGFR<45) hypoxic disease severe infection and trauma, major surgery, clinical hypotension, etc. Known allergy to metformin hydrochloride acute and chronic metabolic acidosis alcoholics who receive intravascular injection of iodinated contrast agent (suspended) vitamin B12, folic acid deficiency is not corrected, VII. Conclusion With definite efficacy, sufficient evidence and low price, metformin has finally been crowned king in the field of diabetes treatment with many advantages, which also leaves us with many questions. With a "king", who is the most compatible "queen"? Who will take the place of the many who covet the throne? To answer these questions, it is not up to an "expert" to say, but a lot of well-designed medical research is needed to develop more reliable and scientific medication guidance for patients.