Diabetes has become the third major non-communicable disease after cardiovascular diseases and tumors, and in 2009, the International Diabetes Federation (IDF) announced that there are 285 million diabetic patients worldwide, and it is predicted that the number of diabetic patients will reach 435 million in 2030. type 2 diabetes accounts for about 90% of the total number of diabetic patients, and the situation of diabetes control is extremely serious. In addition to the five types of oral hypoglycemic agents and human insulin, such as sulfonylureas, glinides, biguanides, α-glucosidase inhibitors and thiazolidinediones, in recent years, new hypoglycemic agents such as glucagon-like peptide-1 (GLP-1) analogues, GLP-1 agonists, dipeptidyl peptidase IV (DPP-IV) inhibitors and insulin analogues have entered the stage of history in the field of diabetes treatment. have entered the stage of history and become powerful weapons to overcome diabetes. Sulfonylureas Sulfonylureas are pro-insulin secretagogues, and their main pharmacological effect is to stimulate insulin secretion by pancreatic B cells and increase insulin levels in the body to lower blood sugar. Clinical studies have shown that sulfonylureas can reduce glycosylated hemoglobin (HbA1c) by 1%-2%, and they are the main drugs recommended in the diabetes guidelines of many countries and international organizations for controlling high blood sugar in patients with type 2 diabetes. The name is generally “Gleevec”, and the common ones on the market in China are Glibenclamide (Eugenol), Glipizide (Mepida, Disulfiram, Rexin), Gliclazide (Damacell), Gliquidone (Glucophage), and Glimepiride (Amoxicillin). It is worth mentioning that the Chinese patent medicine Hypochondrium also contains glibenclamide (10 capsules of Hypochondrium contain 2.5mg of glibenclamide). These drugs are suitable for patients with type 2 diabetes whose own pancreatic B-cells have certain functions. The choice of which drug to take is based on high fasting or postprandial blood sugar, and is usually taken orally 30 minutes before meals. Because of the risk of hypoglycemia, all should start with a small dose and adjust the dosage according to blood glucose monitoring. When eating little or do not want to eat, the class of drugs should be reduced or suspended. Once hypoglycemia occurs, it should be corrected as soon as possible, especially when using glibenclamide, because of the strong hypoglycemic effect, the drug metabolism time is long, hypoglycemia is more stubborn, it is very easy to have a life-threatening condition, and it needs to be observed for more than 72 hours. Glinides Glinides are non-sulfonylurea insulin secretagogues, including Repaglinide (Novaluron) and Naglinide (Tangli). The mechanism of action is the same as that of sulfonylureas, which is to stimulate insulin secretion. The difference is that it is absorbed quickly, has a rapid onset of action and a short duration of action, and stimulates insulin secretion in the early phase, so that meals can be eaten immediately after taking the drug, without the need for 30 minutes in advance, and “fast in and fast out” significantly reduces postprandial blood sugar. Although hypoglycemia may occur, it occurs less frequently and to a lesser extent than sulfonylurea. It reduces HbA1c by 1%-1.5%. Biguanides At present, the main clinical use of biguanides is metformin (Gevalt, Bucco), and very few regions are still using phenelzine (hypoglycemic). They mainly act on the liver to reduce hepatic glucose output and increase the utilization of glucose in peripheral tissues to lower sugar. As one of the earliest oral hypoglycemic agents, metformin has experienced 50 years of hardships, along with the continuous development and re-understanding of the international and domestic concepts of diabetes prevention and treatment, and has the roles of improving insulin resistance, lowering blood lipids, reducing fatty liver, lowering body weight, macrovascular protection, and preventing diabetes in addition to lowering sugar. Its status in the treatment of type 2 diabetes has been further enhanced, and it has been used as the first-line starting drug in various clinical guidelines, especially for obese diabetic patients, and throughout the course of diabetes. Metformin lowers HbA1c by 1%-2% and does not cause hypoglycemia when used alone. However, because it is more prone to gastrointestinal reactions, such as nausea, vomiting and diarrhea, it is generally taken after meals and gradually increased from small doses to reduce gastrointestinal discomfort. The most serious adverse reactions of biguanide are lactic acidosis (LA) induced by hypoxia, hepatic and renal insufficiency, long-term alcohol abuse and the use of contrast imaging. Metformin was largely discontinued as a result, and the odds of developing LA with metformin was 6.3 visits/100,000? year, compared with a non-metformin incidence of 7.8 per 100,000? year, so it is safer. However, its use is prohibited in the above cases. In case of LA, emergency hospitalization is required. Alpha glucosidase inhibitors Alpha glucosidase inhibitors lower postprandial blood glucose by delaying the absorption of carbohydrates in the upper part of the small intestine. It is suitable for Asian patients with carbohydrates as the main food component and elevated postprandial blood glucose. Acarbose (Bactrim, Carboplatin) and voglibose (Bexin) are available in China. It needs to be chewed at the same time as the main food to take effect. The most common adverse effects are abdominal distension, constipation, and excessive vector gas. It is advisable to start with small doses and gradually increase them to reduce gastrointestinal discomfort. Acarbose can lower HbA1c by 0.9% and does not cause hypoglycemia when used alone. And when hypoglycemia occurs in combination with other hypoglycemic drugs, glucose should be taken to correct it. Thiazolidinediones Thiazolidinediones mainly improve insulin sensitivity through the response of target cells to insulin. The ones marketed in China are rosiglitazone maleate (Vindia) and pioglitazone hydrochloride (Etain). Their pharmacological effects mainly include improving insulin resistance, lowering lipids, lowering blood pressure and reducing the risk of cardiovascular disease. It is easy to take once a day. Weight gain and edema are the most common adverse effects of these drugs. It is more significant when combined with insulin, so it should be used with caution in people with cardiac insufficiency, and small doses of diuretics can be used to reduce edema. Glucagon-like polypeptide-1 (GLP-1) analogues, GLP-1 receptor agonists and dipeptidyl peptidase IV (DPP-IV) inhibitors are all new hypoglycemic agents related to enteroglucagon. They are mainly used to lower postprandial hyperglycemia. Among them, GLP-1 analogue (liraglutide) and GLP-1 receptor agonist (exenatide) are both injectable. The pharmacological effects are to increase GLP-1, cause insulin secretion by glucose-dependent insulin B cells, suppress appetite and feeding, delay gastric contents emptying, reduce body weight, inhibit glucagon secretion, promote islet B cell proliferation and reduce apoptosis. Adverse reactions are mainly nausea and vomiting, which usually start from small doses and are injected subcutaneously within one hour before breakfast and dinner, and the gastrointestinal reactions will disappear as the treatment time is prolonged. DPP-IV inhibitors (sitagliptin and vildagliptin) are oral agents that protect endogenous GLP-1 from degradation and increase serum GLP-1 levels, resulting in increased glucose-stimulated insulin secretion. Adverse effects are mainly headache, nasal congestion and sore throat. Insulin analogues Since 1921, insulin has played an extremely important role as the most favorable hypoglycemic agent. However, it is difficult to overcome the gap between exogenous insulin subcutaneous injection and physiological secretion in the body. Therefore, the birth of insulin analogs solved a certain problem to some extent. The ultra-short-acting insulin analogues (lysergic insulin and menthol insulin) can directly enter the capillaries in the form of the presence of monomers to take effect, without the need to inject 30 minutes before a meal, with fast onset of action, and even if they are replenished after a meal, they still act at the postprandial blood glucose peak, with fast metabolism and low incidence of hypoglycemia before the next meal, which can effectively avoid the risk caused by blood glucose fluctuations. It is especially suitable for insulin pump treatment. The mixture of ultra-short-acting insulin analogues and zinc argin in different ratios (25/75,50/50,30/70) allows the majority of patients applying insulin therapy to simplify their treatment regimen and improve compliance compared to the traditional human short-acting plus medium-acting insulin formulations. Ultra-long-acting insulin analogues (glargine insulin and detergent insulin) have been widely used in clinical practice as basal insulin devices because of their long half-life. It also occupies an important position in the guidelines because of its low incidence of hypoglycemia and reduction of fasting glucose. However, there were reports from abroad that its increased risk of tumorigenesis had once caused panic, and the limitations and flaws of the research methods in this report were analyzed and clarified. Facing the challenge of diabetes, we have more advanced new weapons after understanding and mastering the experience of the traditional five classes of hypoglycemic drugs. “If you want to do a good job, you must first improve your weapon”. In the journey of fighting diabetes, only by knowing oneself and one’s opponent can we not lose a hundred battles. But we must not forget: while lowering high blood sugar, we must also always be alert to the occurrence of hypoglycemia! Because one serious medical hypoglycemia can offset the benefits of a lifetime of normal blood sugar!