There are many kinds of hypoglycemic drugs on the market, which can be divided into the following categories.
Insulin secretagogue
Insulin secretagogue is a standby first-line hypoglycemic agent, including sulfonylureas and non-sulfonylureas. It mainly plays a role in promoting insulin secretion, inhibiting ATP-dependent potassium channels, making K+ outflow, depolarization of β cells and Ca2+ inflow, thus inducing insulin secretion. In addition, it can strengthen the combination of insulin and its receptor, relieve the effect of insulin resistance after receptor and strengthen the effect of insulin.
Sulfur secretagogue
(1) Glipizide (Mepida, Ruiyining, Disha, Epipida, Youdaling): It is a second-generation sulfonylurea drug, which takes effect quickly in human body and lasts for 6-8 hours, especially suitable for reducing postprandial hyperglycemia; Because its metabolites are inactive and excreted quickly, it causes less hypoglycemia than glibenclamide and is suitable for elderly patients.
(2) Gliclazide (Dameikang): It is a second-generation sulfonylurea drug, and its efficacy is more than 10 times stronger than that of the first-generation tolbutamide; In addition, it can inhibit platelet adhesion and aggregation, and effectively prevent microthrombosis, thus preventing microangiopathy of type 2 diabetes. It is suitable for obese or diabetic adults with vascular diseases. Use with caution for the elderly and people with renal insufficiency.
(3) glibenclamide (glibenclamide): It is a second-generation sulfonylurea drug, which has the strongest hypoglycemic effect among all sulfonylurea drugs, 200-500 times that of tolbutamide, and its effect can last for 24 hours. It can be used for mild to moderate non-insulin-dependent type 2 diabetes, but it is prone to hypoglycemia, so it should be used with caution by the elderly and people with renal insufficiency.
(4) glibenclamide (clenbuterol): 20 times stronger than the first generation of tolbutamide, more easily absorbed than glibenclamide, and less prone to hypoglycemia; Its effect can last for 24 hours. Can be used for non-insulin dependent type 2 diabetes.
(5) glimepiride (Amory) is the third generation of oral sulfonylureas, and its mechanism of action is the same as other sulfonylureas, but it can increase the intake of glucose in the heart through ways unrelated to insulin, and its influence on cardiovascular system is less than other oral hypoglycemic drugs; Its half-life in vivo can be as long as 9 hours, and it only needs to be taken orally/kloc-0 times a day. It is suitable for non-insulin dependent type 2 diabetes.
(6) Gliquidone (Tang Shiping et al. ): The second generation of oral sulfonylurea hypoglycemic agents is a high-activity islet β -cell agent, which can induce the production of appropriate amount of insulin and reduce the blood sugar concentration by binding with specific receptors on islet β -cell membrane. After taking this product orally for 2~2.5 hours, it reaches the highest blood concentration and is completely absorbed soon. The plasma half-life is 1.5 hours, and the metabolism is complete. Its metabolites have no hypoglycemic effect, and most of them are excreted through bile digestive system. It is suitable for mild and moderate non-insulin-dependent type 2 diabetes with unsatisfactory effect of simple diet control. The islet B cells of patients have certain insulin secretion function without serious complications.
The above are commonly used sulfonylurea hypoglycemic agents at present, and the order of their hypoglycemic intensity from strong to weak is: glibenclamide > glipizide > gliquidone > gliclazide.
Non-sulfonylurea phenyllactic acid derivative secretagogue
It can directly improve the defect of early insulin secretion and has unique advantages in reducing postprandial blood sugar. It was found that the insulin secretion of repaglinide treatment group could be restored to the level of healthy control group. Repaglinide can also restore pulse insulin secretion and improve insulin sensitivity to some extent. The commonly used drugs are repaglinide and nateglinide. Repaglinide (Novolone): This drug will not cause severe hypoglycemia and liver injury. Patients with moderate liver and kidney damage also have better tolerance and less drug interaction, which is suitable for controlling postprandial blood sugar.
Metformin; Metformin (antidiabetic drugs, hypoglycemic drugs)
Metformin hydrochloride is a first-line hypoglycemic agent, which does not stimulate islet β cells and has little effect on normal people, but has obvious hypoglycemic effect on patients with type 2 diabetes. It does not affect insulin secretion, mainly by promoting the intake of glucose by peripheral tissues, inhibiting gluconeogenesis, reducing the output of hepatic glycogen, and delaying the absorption of glucose by intestinal tract, thus achieving the effect of lowering blood sugar. The commonly used drug is metformin. Metformin (Gehuazhi, Meidekang): The hypoglycemic effect is weaker than phenformin, but it is less toxic and has no hypoglycemic effect on normal people; Compared with sulfonylureas, this product does not stimulate insulin secretion, so it rarely causes hypoglycemia; In addition, this product has the effects of increasing insulin receptor, reducing insulin resistance, improving fat metabolism and fibrinolysis, and reducing platelet aggregation, which is conducive to alleviating the occurrence and development of cardiovascular complications. This is the first choice for children, overweight and obese type 2 diabetes. It is mainly used for obese or overweight patients with type 2 diabetes, and can also be used for patients with type/kloc-0 diabetes, which can reduce insulin dosage and can also be used for treating insulin resistance syndrome. Because of its great reaction to gastrointestinal tract, it should be taken during or after meals. Patients with renal insufficiency are prohibited.
α -glucosidase inhibitor
α -glucosidase inhibitor is a standby first-line hypoglycemic agent. These drugs competitively inhibit maltase, glucoamylase and sucrase, block the hydrolysis of 1, 4- glycosidic bond, delay the decomposition of starch, sucrose and maltose into glucose in the small intestine, and reduce postprandial blood sugar. Its commonly used drugs are: sugar-100, acarbose and voglibose.
(1) Sugar-100: The main component BTD- 1 is a fermented soybean extract for regulating the rapid increase of blood sugar after meals, which is produced by Bacillus subtilis and defatted soybean meal. 1- deoxynojirimycin (DNJ) produced by Bacillus subtilis has good inhibitory activity on α -glucosidase in small intestinal villi.
(2) Acarbose (white Tang Ping): It does not cause hypoglycemia and does not affect body weight when used alone; Can be used in combination with other oral hypoglycemic drugs and insulin. It can be used for various types of diabetes, improving postprandial blood sugar of patients with type 2 diabetes, and can also be used for other patients with ineffective oral hypoglycemic drugs.
(3) Voglibose (Beixin): It is a new generation of α -glucosidase inhibitor. The drug has stronger inhibitory effect on intestinal mucosal α -glucosidase (maltase, isomaltase, glycosidase) than acarbose, but weaker inhibitory effect on pancreatic α-amylase. It can be used as the first choice for type 2 diabetes, and can also be used in combination with other oral hypoglycemic drugs and insulin.
Insulin sensitizer
These drugs can reduce fasting and postprandial blood sugar by improving the sensitivity of target tissues to insulin, improving the ability to use insulin and improving glucose metabolism and lipid metabolism. When used alone, it does not cause hypoglycemia, and it is often combined with other oral hypoglycemic drugs, which can produce obvious synergistic effect. The commonly used drugs are rosiglitazone and pioglitazone.
(1) Rosiglitazone (Avandia): A new type of insulin sensitizer, which is ineffective for patients with 1 type diabetes and type 2 diabetes due to insulin deficiency. Elderly patients and people with impaired renal function do not need to adjust the dose. Use with caution in patients with anemia, edema and cardiac insufficiency, but not in patients with hepatic insufficiency. Avandia, as a commonly used hypoglycemic agent, has stopped being popularized in China because of the risk of cardiovascular disease. Experts suggest using Avandia with caution as appropriate.
(2) Pioglitazone: thiazolidinedione hypoglycemic agent, which belongs to insulin sensitizer. Its mechanism is related to the existence of insulin, which can reduce the insulin resistance of peripheral tissues and liver, increase the treatment of insulin-dependent glucose and reduce the output of liver sugar. It is suitable for type 2 diabetes (non-insulin dependent diabetes mellitus, NIDDM). In clinical controlled trials, pioglitazone combined with sulfonylureas, metformin or insulin can improve the curative effect. At the same time, with the worldwide use of rosiglitazone (Avandia) restricted or banned, the market of pioglitazone will expand.
Dipeptidyl peptidase -4
Dipeptidyl peptidase -4(DPP-4) inhibitor was approved in more than 80 countries in June 2006, and was listed in China in June 2065, with 438+00. It improves a physiological mechanism called "intestinal islet stimulating hormone" GLP- 1, reduces the inactivation of GLP- 1 in human body, and regulates glucose level by affecting β cells and α cells in pancreas. At present, several dipeptidyl peptidase products have been listed, such as Sigliptin, saxagliptin and Vigliptin.
GLP- 1 receptor agonist
Glucagon polypeptide and GLP- 1 receptor agonist are two main types of glucose-dependent insulinotropic polypeptide GIP. GLP- 1 receptor agonists enhance insulin secretion, inhibit pancreatic hyperglycemia secretion and delay gastric emptying in a glucose concentration-dependent manner, and reduce food intake through central appetite suppression. It has the function of losing weight and may have a good prospect in lowering blood pressure. The existence of GLP- 1 is an important condition for β cell regeneration. In 2004, it was found that GLP- 1 enhanced the regeneration of β cells, inhibited apoptosis and promoted the differentiation of pancreatic duct stem cells into β cells. GLP- 1 analogues are called differentiation factors (increasing new life), growth factors (enhancing replication) and survival factors (prolonging survival time and reducing apoptosis) of β cells. In 2005, FDA approved the use of subcutaneous preparations, such as exenatide and liraglutide, which are suitable for patients with type 2 diabetes who can not completely control their blood sugar by using metformin and sulfonylureas.