Diabetes is a chronic progressive disease, β The decline of cell function is the central link in the occurrence and development of type 2 diabetes. With the development of type 2 diabetes, most hypoglycemic drugs cannot maintain good blood glucose control for a long time. The survey on Chinese patients shows that only 51% of patients can adhere to the current treatment scheme for more than 1 year, 31.9% of patients have changed the treatment scheme in the past year, of which 70.6% have changed the treatment scheme at least once; Poor efficacy is one of the main reasons for changing the treatment plan.

The inability to control blood sugar for a long time has become an important problem in the clinical treatment of diabetes. The annual incidence of secondary failure of sulfonylurea drugs is about 5%~10%, and the 5-year failure rate of metformin monotherapy is as high as 51.7%. β The main reason for the secondary failure of hypoglycemic drugs is the gradual failure of cell function. Here will mainly combine β Cytoprotective effect system to explain the efficacy and tolerance of exenatide in long-term treatment

Protection β The natural course of type 2 diabetes is β The gradual failure of cell function and the gradual increase of blood sugar, the more serious the loss of pancreatic islet secretion function, the higher the blood sugar, and the further damage of hyperglycemia toxicity β Cells, forming a vicious circle. Research shows that early protection β The cells help to induce long-term remission of diabetes and delay the progress of diabetes. Therefore, protect β Cell Function, Delayed β Cell failure is the key to achieve lasting blood glucose control. β Cell is a kind of long-lived cell, and its functional failure needs to go through a long period of time.

β The failure of cell function is affected by many factors, including glycotoxicity, lipotoxicity, age and insulin resistance, which can lead to β Reversible and irreversible cell damage. For example, long-term exposure to severe hyperglycemia will affect the transcription and expression of insulin gene, leading to irreversible β Cell function damage; The short-term high glucose toxicity only affects β The secretion and storage of insulin in cells β Cell dysfunction is reversible. Early intensive insulin therapy is achieved through timely reversal β Reversible damage of cells to prevent irreversible damage β Cell function, inducing long-term remission of diabetes. Thiazolidinediones (TZD) can reduce the toxicity of high glucose by improving insulin resistance β Delayed cell burden β Cell failure.

At present, there are two GLP-1 receptor agonists listed in China: exenatide and liraglutide. Exenatide, trade name Baibida, is a short acting GLP-1 analog, which has 53% homology with human natural GLP-1. A number of basic and clinical studies have found that exenatide can improve β Function of cells. Basic research found that in newborn type 2 diabetes model rats, short-term treatment (7 days) and long-term treatment (2 months) with exenatide can significantly stimulate β Cell replication and regeneration.

Studies conducted in vivo and in vitro in mice pancreatic tissues have found that exenatide can promote β The effect of cell proliferation is mainly realized through PI3k/Akt signal transduction pathway. Mitochondrial oxidative stress is the pancreatic islet β The basis of cell apoptosis, exenatide can protect β Mitochondria of cells are protected from oxidative fmoc-osu stress and reduce the rate of apoptosis. Therefore, exenatide can promote β Cell Proliferation, Inhibition β Apoptosis, Increased β Number of cells to improve β Cell function