The earliest glucose-lowering drugs: many have been abandoned The first generation of sulfonylurea glucose-lowering drugs In 1942, Janbon, a French physician, noticed hypoglycemia in many patients while treating typhoid fever with sulfonylureas. And another French scientist, Loubatieres, also confirmed the hypoglycemic effect of sulfonylureas in the laboratory. After continuous efforts of scientists, the first generation of sulfonylurea hypoglycemic drug, methanesulfonylurea (D860, methanesulfonate), was introduced in 1956. It had a weak hypoglycemic effect, so the dosage was larger and had to be taken three times a day. Later, chlorosulfonylurea, which is taken once a day, was introduced, but its hypoglycemic effect is too strong and it is easy to cause hypoglycemia. Biguanide hypoglycemic drugs In response to the problem of hypoglycemia of sulfonylureas, scientists introduced metformin and phenethylbiguanide (hypoglycemic) at the end of the 1950s. Later, phenethylbiguanide was banned in many countries because it was prone to lactic acidosis, which is very lethal. Current glucose-lowering drugs: therapeutic effects continue to improve Metformin (Gevalt, Medecan, Diabetes lozenges) Metformin has been used since 1957 and is currently the first-line glucose-lowering drug, especially for overweight patients with type 2 diabetes. Second-generation sulfonylurea hypoglycemic agents The hypoglycemic effect of second-generation sulfonylurea hypoglycemic agents is less affected and interfered by other drugs, and the side effects are light. In descending order of glucose-lowering effect, they are Glibenclamide (Eugenol), Glibenclamide (Glyburide), Glipizide (Qinsu, Mepida, Disa, Udalin), Gliclazide (Damecam) and Gliquidone (Glucophage). Third-generation sulfonylurea hypoglycemic agents The ideal sulfonylurea hypoglycemic agent should be able to promote insulin secretion without stimulating secretion too much, and also have some extra-pancreatic effects. The representative of this type of drug is Glimepiride (Amoril). It has the strongest extrapancreatic hypoglycemic effect compared to the previous two generations. Glimepiride pro-insulin secretagogue It does not need to be taken half an hour earlier and thus is called a mealtime glucose regulator. One is a derivative of benzoic acid, Repaglinide (Novaluron), and the other is a derivative of phenylalanine, Naglinide (Tangli). These drugs are mainly metabolized in the liver and can be used in patients with mild renal insufficiency. Alpha glucosidase inhibitors This is a pseudoglucose that takes over the absorption of glucose from the small intestine. Patients must take the drug with the first bite of the meal, otherwise it does not work to preempt the occupation. There are two kinds of drugs available, one is acarbose (Bacitracin, Carboplatin) and the other is voglibose (Bexin). Such drugs are the only drugs used for hypoglycemic tolerance in China. Thiazolidinediones (glitazones) This is a class of oral hypoglycemic drugs that can increase insulin sensitivity. Currently in clinical use are rosiglitazone (Vindia) and pioglitazone (Ecto, Caspian). Compound formulation The first oral hypoglycemic compound currently on the market is the compound formulation of metformin and rosiglitazone, Vindamine. It contains 500 mg of metformin and 2 mg of rosiglitazone. The future of glucose-lowering drugs: oral insulin to look forward to Oral insulin This is the long-desired oral drug that can be free from insulin injections. However, because insulin is affected by stomach acid, oral administration has been an insurmountable obstacle. Oral insulin may be one of the future directions through technological improvement and the use of oral buccal mucosa absorption. Dipeptidyl peptidase-IV inhibitors New dipeptidyl peptidase-IV inhibitors such as sitagliptin (Genovel) and vigliptin (Galvus). Sodium glucose transporter-2 inhibitors A study has shown that treatment with sodium glucose transporter-2 inhibitors for 12 weeks can reduce fasting glucose by 30-50 mg/dl. A phase III clinical study of this drug, Dapagliflozin, is currently underway. Long-acting interleukin 1β antagonist Inhibition of interleukin 1β improves islet function and prevents premature islet cell death in patients with type 2 diabetes. Glucokinase activator It promotes both an increase in glucose-dependent insulin secretion and stimulates the efficient use of glucose in the liver.