利拉鲁肽治疗 2 型糖尿病的心血管安全性和疗效的随机对照试验方案。

A randomized controlled trial protocol of the cardiovascular safety and efficacy of liraglutide in the treatment of type 2 diabetes.

机构信息

Department of Cardiology, Changhai Hospital of Naval Military Medical University, Shanghai 200438.

Department of Medicine, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002.

出版信息

Medicine (Baltimore). 2021 Jan 22;100(3):e23948. doi: 10.1097/MD.0000000000023948.

DOI:10.1097/MD.0000000000023948

PMID:33545972

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7837848/

Abstract

BACKGROUND

Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients.

METHODS

This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m2 body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model.

CONCLUSIONS

For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride.

TRIAL REGISTRATION

This study protocol was registered in Research Registry (researchregistry6306).

摘要

背景

最近，许多临床实验评估了利拉鲁肽在 2 型糖尿病治疗中的影响。然而，这些研究的结果并不一致，并且评估心血管安全性的高质量前瞻性试验数量有限。因此，本研究旨在评估利拉鲁肽在 2 型糖尿病患者中的心血管疗效和安全性。

方法

本研究是一项为期 26 周的活性对照、随机试验。我们的研究方案遵循赫尔辛基宣言和国际协调会议发布的良好临床实践指南。所有患者都将获得书面知情同意书，以参与我们的临床实验。年龄在 18 至 80 岁之间、体重指数在 45.0kg/m2 或以下、糖化血红蛋白在 7.5%至 10.0%之间、接受二甲双胍（每天 1500mg 或更多）治疗 3 个月或以上的 2 型糖尿病患者符合条件。所有患者随机分为 2 组（1:1）：利拉鲁肽安慰剂（每日一次，盲法）和利拉鲁肽（每日一次，盲法），均与格列美脲和二甲双胍联合使用（开放标签）。对于疗效变量，主要终点是治疗 26 周后基线糖化血红蛋白的变化。次要终点包括：餐后血糖、空腹血糖和糖化血红蛋白达标患者的比例；平均餐后血糖、空腹血糖和体重的变化，胰岛 B 细胞功能指数，以及通过稳态模型评估的血压和胰岛素抵抗的变化。