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Diabetes is a group of metabolic diseases characterized by hyperglycemia. Poor long-term control of hyperglycemia can lead to damage to multiple organ tissues, accompanied by cardiovascular and cerebrovascular, eye, kidney, limbs, and other organ lesions. In addition to exercise and dietary intervention, medication intervention is also key to controlling blood sugar. Diabetes treatment drugs mainly include oral hypoglycemic agents and injectable hypoglycemic agents.Oral Hypoglycemic AgentsBased on their effects, they can…
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Diabetes is a group of metabolic diseases characterized by hyperglycemia. Poor long-term control of hyperglycemia can lead to damage to multiple organ tissues, accompanied by cardiovascular and cerebrovascular, eye, kidney, limbs, and other organ lesions. In addition to exercise and dietary intervention, medication intervention is also key to controlling blood sugar. Diabetes treatment drugs mainly include oral hypoglycemic agents and injectable hypoglycemic agents.
Oral Hypoglycemic Agents
Based on their effects, they can be divided into drugs that primarily promote insulin secretion and those that lower blood sugar through other mechanisms. The former mainly includes sulfonylureas and glinides, while the latter mainly includes biguanides, thiazolidinediones (TZDs), α-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose cotransporter 2 inhibitors (SGLT-2i). Different types of drugs vary in their hypoglycemic effect, risk of hypoglycemia, weight loss, and impact on the heart and kidneys, and they are not suitable for the same populations.
Sulfonylureas include glibenclamide (Glibenclamide), glipizide (Glipizide), glipizide (Glipizide), glipizide (Glipizide), and glimepiride (Glimepiride).
Sulfonylureas belong to insulin secretagogues, which mainly lower blood sugar by stimulating the secretion of insulin from pancreatic B cells and increasing the level of insulin in the body. Sulfonylureas can promote the production of endogenous insulin, so there is a certain risk of hypoglycemia, especially in elderly patients and patients with combined liver or kidney dysfunction.
Long-term use of sulfonylureas may lead to secondary failure of sulfonylureas, mainly due to pancreatic B cell function failure or insulin resistance that is difficult to alleviate. First-generation sulfonylureas such as tolbutamide and chlorpropamide have been phased out due to strong adverse reactions; second-generation include glibenclamide, glipizide, glipizide, and glimepiride; third-generation glimepiride has both insulin secretagogue and sensitization functions, is long-acting, and causes less hypoglycemia. Patients with mild to moderate renal insufficiency can use glimepiride, which is mainly excreted in feces via bile along with its metabolites.
Glinides include repaglinide (Repaglinide), nateglinide (Nateglinide), and mitiglinide. They can directly improve the early phase secretion defect of insulin and have a unique advantage in reducing postprandial blood sugar. Repaglinide can also restore pulsatile insulin secretion and improve insulin sensitivity to a certain extent. These drugs should be taken before meals and can be used alone or in combination with other hypoglycemic drugs (except sulfonylureas).
Common adverse reactions of glinides are hypoglycemia and weight gain, but the risk and degree of hypoglycemia are lighter than those of sulfonylureas. Glinides can be used in patients with renal insufficiency.
Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce the inactivation of GLP-1 in the body by inhibiting DPP-4, thereby increasing the level of endogenous GLP-1. Blood GLP-1 increases insulin secretion in a glucose concentration-dependent manner and inhibits glucagon secretion. Currently, DPP-4 inhibitors marketed in China include sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin.
The use of DPP-4 inhibitors alone does not increase the risk of hypoglycemia.
The effect of DPP-4 inhibitors on body weight is neutral. Linagliptin does not increase the risk of composite renal outcomes (renal death, progression to end-stage renal disease, or persistent eGFR decline of 40%).
When using sitagliptin, saxagliptin, alogliptin, and vildagliptin in patients with renal insufficiency, attention should be paid to reducing the drug dose according to the drug instructions. There is no need to adjust the dose when using linagliptin in patients with liver or renal insufficiency.
Biguanides include metformin (Metformin). Metformin is the first choice of medication for type 2 diabetes patients and the basic medication in combination therapy. It lowers blood sugar by reducing hepatic glucose output, increasing muscle glucose uptake, and improving peripheral insulin resistance. The hypoglycemic effect is strong, and the use of metformin alone does not increase the risk of hypoglycemia, but the combination of metformin with insulin or insulin secretagogues may increase the risk of hypoglycemia. Whether it is the “Chinese Type 2 Diabetes Prevention and Treatment Guidelines (2020 Edition)” released by the Chinese Diabetes Society or the “Diabetes Medical Diagnosis and Treatment Standards (2021 Edition)” issued by the American Diabetes Association, metformin is recommended as the preferred initial treatment drug for type 2 diabetes. Once treatment is initiated, if the patient can tolerate it and there are no contraindications, metformin should always be retained in the treatment plan.
Thiazolidinediones include rosiglitazone (Rosiglitazone) and pioglitazone (Pioglitazone). TZDs mainly lower blood sugar by increasing the sensitivity of target cells to insulin. Since the main pathogenesis of type 2 diabetes is insulin resistance and relative insulin secretion deficiency, and thiazolidinediones have a good effect on these two causes, they were highly regarded by clinicians at the beginning of marketing.
However, in May 2007, a meta-analysis published in the top medical journal “The New England Journal of Medicine” showed that rosiglitazone
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