Peptide Knowledge Center

Development of exenatide

Exenatide (Byetta, Bretta) is the first GLP-1 receptor agonist to be marketed, and was approved by SFDA of China in August 2009 Exenatide is suitable for T2DM patients who are still dissatisfied with the addition of sulfonamides and (or) thiazolidinediones based on metformin to control blood glucose. It is injected under the endothelium 60 minutes before breakfast and dinner every day On January 27, 2012, the US Food and Drug Administration approved the marketing application of exenatide injection, a sustained-release dosage form, once a week. This is the first treatment drug used once a week in the treatment of type 2 diabetes. The extension of the administration time makes it more convenient for patients to use drugs and greatly improves patients' compliance The research and development of long-acting GLP-1 agonists is also one of the current research focuses

The exenatide impurities sustained-release preparation disperses exenatide molecules into microspheres. After being injected subcutaneously into the body, the microsphere particles slow down the effective ingredients into the internal circulation through spontaneous hydrolysis This mechanism of action is more conducive to maintaining the drug concentration above the effective blood concentration for a long time, so as to better play the pharmacological role

Clinical efficacy of exenatide sustained release preparation

Many clinical studies have confirmed that exenatide, whether used alone or in combination, can effectively reduce the blood sugar level of patients with type 2 diabetes The "DURATION" series of studies is a large-scale clinical trial of exenatide sustained-release preparation in the treatment of type 2 diabetes, including six randomized controlled studies. A total of 3225 patients with type 2 diabetes participated in the clinical trial. Its purpose is to study the efficacy and safety of exenatide single drug treatment and combined treatment with one or more oral hypoglycemic drugs at different stages of type 2 diabetes treatment DURATION-1 is a 5-year randomized, non blind clinical trial. A total of 295 patients participated in the trial in the early stage. The trial randomly divided the subjects into two groups according to the ratio of 1:1. One group switched to use exenatide sustained-release preparation after injection of exenatide short acting preparation in the first stage of the trial; The other group was always treated with exenatide sustained-release preparation From the experimental results, the HbA1c level in both groups decreased by 2% and the body weight decreased by more than 4 kg

The DURATION-2 trial was also carried out in two stages. During the trial, 491 patients with type 2 diabetes who had been treated with metformin were divided into three groups, with the addition of exenatide sustained-release preparation, sigliptin and pioglitazone, respectively At the end of the first 26 weeks of the trial, HbA1c in the three groups of exenatide sustained release preparation, sitagliptin and pioglitazone decreased by 1.5%, 0.9% and 1.2% respectively. In terms of weight control, the weight changes in the three groups were - 2.3 kg, - 1.5 kg and+2.8 kg, respectively. From the test data, exenatide sustained release preparation showed great advantages, which further confirmed the safety and effectiveness of exenatide sustained release preparation DURATION - 3 A total of 456 patients were enrolled in the trial On the basis of existing anti diabetes treatment, subjects were randomly added with exenatide sustained-release preparation or insulin glargine After 3 years of tests, the exenatide sustained-release preparation group showed a more obvious effect on the reduction of HbA1c compared with insulin glargine group.

Safety of exenatide sustained-release preparations

The safety data of exenatide sustained-release preparations are mostly from the DURATION test project. The adverse reactions are mainly gastrointestinal reactions such as nausea, with the incidence ranging from 9.3% to 26.4% fmoc-osu The report pointed out that the symptoms of nausea mainly occurred in the first 6-8 weeks of treatment, and then gradually relieved In the comparison test with other oral hypoglycemic drugs, none of the patients in the exenatide sustained-release preparation group had severe hypoglycemic reaction, and the main adverse reactions were nausea and diarrhea


For patients with type 2 diabetes, blood sugar control is highly dependent on adherence to medication After January 2012, a new long-acting exenatide sustained-release preparation with lower frequency of use and excellent efficacy came out, which showed good therapeutic effect and tolerance in blood glucose control, weight loss and cardiovascular risk reduction This drug is considered to be a potential new member of the GLP-1 analog market. In the first quarter of 2014, AstraZeneca announced that FDA approved the launch of exenatide sustained-release suspension injection pen similar to liraglutide. This is a pre filled disposable pen syringe, which does not require patients to convert drugs between vials and syringes during self injection. This new injection system will improve the convenience of patients' use, It is expected to greatly improve the enthusiasm of doctors and patients