Glucagon-like peptide-1 receptor agonists, namely GLP-1 receptor agonists, are a class of drugs for the treatment of type 2 diabetes. This type of drug can produce a hypoglycemic effect by stimulating the glucagon-like peptide-1 receptor and exert the effect of incretin. It is a kind of insulin secretion-stimulating drug that can reduce blood sugar and body weight. showed an advantage in protection.
Mechanism
Glucagon-like peptide-1 (GLP-1) is a multifunctional peptide hormone secreted by ileal and colonic L cells and plays an important role in regulating other physiological processes such as glucose homeostasis. Genetically encoded, with 50% homology to glucagon, it can promote the release of 50% to 70% of insulin after meals. GLP-1 is rapidly decomposed and inactivated by dipeptidyl peptidase 4 (DPP-4) after being secreted into the blood, and its half-life in vivo is only 2 min, which limits its application in hypoglycemic therapy. GLP-1 receptor agonists may have GLP-1-like effects while enhancing the duration of action due to structural differences from native GLP-1.
GLP-1 receptor agonists can stimulate insulin secretion in a glucose-dependent manner. GLP-1 receptor agonists promote insulin release mainly by activating GLP-1 receptors. GLP-1 receptor agonists bind to GLP-1 receptors and activate calmodulin through the cAMP/PKA pathway to increase the calcium influx of L-type voltage-gated calcium channels and the release of calcium from the endoplasmic reticulum. The efflux action of insulin is enhanced. GLP-1 promotes insulin secretion in a glucose-dependent manner. When the blood glucose concentration is high, it can significantly stimulate the release of insulin and inhibit the release of glucagon, thereby reducing blood glucose. , blood sugar generally does not decrease further, thus greatly reducing the risk of hypoglycemia. Studies have shown that when blood sugar is lower than 4.5mmol/L, GLP-1 no longer has insulin secretion effect. Therefore, GLP-1 receptor agonists make patients face less risk of hypoglycemia and are more conducive to achieving stable blood sugar reduction. .
In addition to promoting insulin synthesis and secretion, GLP-1 can also inhibit glucagon secretion, stimulate β-cell proliferation and regeneration, inhibit β-cell apoptosis, reduce food intake, delay gastric emptying and have potential protective effects on cardiomyocytes. . A number of clinical trials have shown that with the same hypoglycemic effect, GLP-1 receptor agonists have some advantages that other hypoglycemic drugs do not have. First, GLP-1 receptor agonists can delay gastric emptying, reduce food intake, make patients lose weight, and further improve blood lipid levels in patients with diabetes. Secondly, GLP-1 receptor agonists have a direct protective effect on nerve cells, cardiomyocytes, etc., and can also reduce intimal thickening and smooth muscle proliferation after vascular injury, and have potential anti-inflammatory and anti-atherosclerotic effects. .
GLP-1 drugs list
GLP-1 hypoglycemic drugs, the full name of glucagon-like peptide-1 receptor agonists, mainly include GLP-1-activating drugs, such as exenatide, lixisenatide, etc., and enhance the activity of GLP-1, The drugs that reduce its degradation, the degrading drugs of GLP-1 are DPP-4 inhibitors, such as alogliptin, sitagliptin, etc.
1. GLP-1 activating drugs: mainly include exenatide, lixisenatide, liraglutide, albiglutide, and dulaglutide. GLP-1 is a normal hormone released by human enteroendocrine cells. It can bind to the GLP-1 receptor of islet β cells with a high degree of heterosexuality, so that it stimulates the secretion of insulin and inhibits the production of glucagon. The characteristics of the drug are that it can keep blood sugar constant, while reducing the occurrence of hypoglycemia, while reducing blood sugar, it can also suppress appetite, and has a certain weight loss effect, especially for obesity caused by type 2 diabetes, the treatment effect is good;
2. DPP-4 inhibitors: mainly include alogliptin, sitagliptin, linagliptin, and saxagliptin. DPP-4 inhibitors can enhance the activity of GLP-1 and reduce the degradation of GLP-1, thereby increasing insulin secretion, inhibiting glucagon secretion, inhibiting intestinal glucose absorption, and reducing blood sugar. Clinically, DPP-4 inhibitors are widely used. Such drugs can be used in combination with other hypoglycemic drugs, such as acarbose, voglibose and other glycosidase inhibitors. Use in combination with insulin.
The specific drug that patients use to lower blood sugar should be carried out under the guidance of a doctor. To develop a reasonable treatment plan, in order to achieve better treatment effect.
Common adverse reactions
Common adverse reactions include hypoglycemia, gastrointestinal discomfort, dizziness, fatigue, nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, anorexia, etc.
Precautions
1. Not for use in patients with type 1 diabetes or diabetic ketoacidosis;
2. It cannot be used in patients with past history or family history of medullary thyroid cancer (MTC), and patients with type 2 multiple endocrine tumor syndrome (MEN2);
3. Cannot be used for patients with inflammatory bowel disease and diabetic gastroparesis;
4. Acute pancreatitis and thyroid-related adverse events have been reported, and attention should be paid during use;
5. Adverse events such as increased blood calcitonin, goiter and thyroid tumor may occur;
6. Do not use when the color of the solution changes obviously or when there are particles or turbidity;
7. Those who are allergic to GLP-1 analogues and any ingredients contained in it are prohibited;
8. Cannot be used in pregnant and lactating women;
9. Cannot be used for pediatric patients.
Summarize
GLP-1 receptor agonists have four main characteristics: strong hypoglycemic effect, weight loss, lower incidence of hypoglycemia than other hypoglycemic agents, and more cardiovascular benefits. Some GLP-1 receptor agonists also have the effect of lowering blood pressure and protecting the kidneys, and are a good class of insulin secretion-stimulating drugs. They are a good choice for obese patients with type 2 diabetes.