Pharmacological treatment of hyperglycemia is mostly based on the two main pathophysiological alterations that lead to elevated blood glucose in humans – insulin resistance and impaired insulin secretion. Oral hypoglycemic agents can be divided into pro-insulin secretagogues (sulfonylureas, glinides, DPP-4 inhibitors) and non-pro-insulin secretagogues (biguanides, TZDs, α-glucosidase inhibitors) depending on their effects. Sulfonylureas and glinides directly stimulate insulin secretion; DPP-4 inhibitors increase GLP-1 concentration by reducing the breakdown of GLP-1 in vivo, thus promoting insulin secretion; the main pharmacological effect of biguanides is to reduce hepatic glucose output; the main pharmacological effect of TZDs is to improve insulin resistance; the main pharmacological effect of α-glucosidase inhibitors is to delay carbohydrate in the intestinal tract digestion and absorption in the intestine. Medical nutrition therapy and exercise therapy for diabetes are the basic measures to control hyperglycemia in type 2 diabetes. Type 2 diabetes is a progressive disease. In the natural course of type 2 diabetes, the function of pancreatic β-cells gradually declines with the prolongation of the disease, and the degree of insulin resistance does not change much. Therefore, as the course of type 2 diabetes progresses, the dependence on exogenous means of glycemic control gradually increases. Combination therapy between oral medications is often required in clinical practice. The six types of diabetic oral hypoglycemic agents commonly used in clinical practice include: 1. Biguanides: (reduce hepatic glucose output and improve peripheral insulin resistance, with metformin) The main clinically used biguanides are metformin hydrochloride. The main pharmacological effect of metformin is to lower blood glucose by reducing hepatic glucose output and improving peripheral insulin resistance. Many national and international organizations have developed diabetes guidelines that recommend metformin as the first-line drug and the base drug in combination for the control of hyperglycemia in patients with type 2 diabetes. Clinical trials have shown that metformin can reduce HbA1c by 1% to 2% and can lead to weight loss. In the UKPDS trial metformin was also shown to reduce cardiovascular events and death in obese patients with type 2 diabetes. Metformin alone does not cause hypoglycemia, but its combination with insulin or insulinotropic agents can increase the risk of hypoglycemia. The main side effects of metformin are gastrointestinal reactions. Starting with a small dose and gradually increasing it is an effective way to reduce adverse reactions. A rare serious side effect of metformin is the induction of lactic acidosis. Therefore, biguanides are contraindicated in patients with renal insufficiency (blood creatinine level >1.5mg/dl in men and >1.4mg/dl in women or glomerular filtration rate <60ml/min), hepatic insufficiency, severe infection, hypoxia or major surgery. When using iodinated contrast agents for imaging examinations, metformin should be temporarily discontinued. 2. Sulfonylureas (insulinotropic agents, including glibenclamide, glimepiride, gliclazide, glipizide and gliquidone) Sulfonylureas are insulinotropic agents, and their main pharmacological effect is to lower blood glucose by stimulating insulin secretion from pancreatic beta cells and increasing insulin levels in the body. Clinical trials show that sulfonylureas can reduce HbA1c by 1% to 2%, and are the main drugs recommended in the diabetes guidelines formulated by many countries and international organizations for controlling high blood sugar in patients with type 2 diabetes. At present, the main sulfonylureas listed in China are glibenclamide, glimepiride, gliclazide, glipizide and glipizide. Sulfonylureas can lead to hypoglycemia if used improperly, especially in elderly patients and those with hepatic and renal insufficiency; sulfonylureas can also lead to weight gain. Patients with mild renal insufficiency are advised to choose glipizide. When patients have poor compliance, it is recommended to take a sulfonylurea that is taken only once a day. Sulfonylurea is a fixed-dose combination containing glibenclamide and a variety of Chinese herbal ingredients. 3. Thiazolidinediones (lowering blood sugar by increasing the sensitivity of target cells to insulin action, with rosiglitazone and pioglitazone) Thiazolidinediones (TZDs) lower blood sugar mainly by increasing the sensitivity of target cells to insulin action. The main TZDs currently available in China are rosiglitazone maleate and pioglitazone hydrochloride. Clinical trials have shown that TZDs can reduce HbA1c by 1.0% to 1.5%. TZDs do not cause hypoglycemia when used alone, but can increase the risk of hypoglycemia when used in combination with insulin or insulin-producing agents. The use of TZDs is also associated with an increased risk of fracture and heart failure. This class of drugs should be contraindicated in patients with heart failure [New York Heart Association (NYHA) cardiac class II or higher], active liver disease or transaminases elevated more than 2.5 times the upper limit of normal, and a history of severe osteoporosis and fractures. The use of rosiglitazone is strictly limited in China because of the controversial safety issues. For patients with diabetes who have not used rosiglitazone and its combination, rosiglitazone and its combination should be considered only when other hypoglycemic agents are not available or when the goal of glycemic control cannot be achieved with other hypoglycemic agents. For those who are already using rosiglitazone and its combination, the risk of cardiovascular disease should be evaluated and the decision to continue using the drug should be made after weighing the advantages and disadvantages of using the drug.4. Glinides (insulinotropic agents, including repaglinide, nateglinide and miglinide) are non-sulfonylurea insulinotropic agents, and those marketed in China include repaglinide, nateglinide and miglinide. This kind of drugs mainly through stimulating the early secretion of insulin and reduce postprandial blood sugar, with the characteristics of fast absorption, fast onset and short duration of action, can reduce HbA1c 0.3% ~ 1.5%. These drugs need to be taken immediately before meals, and can be used alone or in combination with other hypoglycemic drugs (except sulfonylureas). The common side effects of glinides are hypoglycemia and weight gain, but the risk and degree of hypoglycemia are milder than those of sulfonylureas. 5. α-glucosidase inhibitors (inhibit the absorption of carbohydrates in the upper part of the small intestine and lower blood glucose, with acarbose, voglibose and miglitol) α-glucosidase inhibitors lower postprandial blood glucose by inhibiting the absorption of carbohydrates in the upper part of the small intestine. It is suitable for patients with carbohydrates as the main food component and elevated postprandial blood glucose. The α-glucosidase inhibitors listed in China include acarbose, voglibose and miglitol. α-glucosidase inhibitors can reduce HbAlc by 0.5% to 0.8% without increasing body weight and have a tendency to reduce body weight, and can be combined with sulfonylureas, biguanides, TZDs or insulin. α-glucosidase inhibitors have common adverse reactions such as gastrointestinal reactions, bloating and exhaustion. Starting with a small dose and gradually increasing it is an effective way to reduce adverse reactions. Hypoglycemia usually does not occur when taking this class of drugs alone; if hypoglycemia occurs in patients with combined use of α-glucosidase inhibitors, glucose or honey is required for treatment, and the effect of consuming sucrose or starchy food to correct hypoglycemia is poor. 6. dipeptidyl peptidase-4 inhibitors (GLP-1 inactivation is reduced, which in turn enhances insulin secretion, inhibits glucagon secretion and lowers blood glucose, with selegiline, saxagliptin and vincristine). GLP-1 enhances insulin secretion and inhibits glucagon secretion in a glucose concentration-dependent manner. The DPP-4 inhibitors currently available in China are sitagliptin, saxagliptin and vildagliptin. Clinical trials including Chinese patients with type 2 diabetes have shown that selegiline can reduce HbA1c by 1.0%. The use of DPP-4 inhibitors alone did not increase the risk of hypoglycemia or increase body weight. When used in patients with renal insufficiency, care should be taken to reduce the drug dose in accordance with the drug's instructions.