加拿大麦克马斯特大学Hertzel C. Gerstein团队研究了efpeglatide治疗2型糖尿病的心血管和肾脏结局。2021年6月28日出版的《新英格兰医学杂志》发表了这项成果。

四种胰高血糖素样肽-1（GLP-1）受体激动剂在结构上与人类GLP-1相似，已被证明可降低2型糖尿病患者发生心血管不良事件的风险。以艾塞那肽为基础的GLP-1受体激动剂efpeglenatide对2型糖尿病患者心血管和肾脏预后的影响尚不确定，因为2型糖尿病患者本身也有发生心血管不良事件的高风险。

研究组在在28个国家的344个机构进行了一项随机、安慰剂对照试验，招募患有2型糖尿病、有心血管病史或当前肾脏疾病（定义为肾小球滤过率为25.0-59.9 mL/min/1.73 m²体表面积）且至少有一种其他心血管危险因素的参与者。将其按1：1：1的比例随机分配，每周接受4或6 mg的efpeglatide皮下注射或安慰剂治疗。主要结局是首次重大不良心血管事件（MACE；非致死性心肌梗死、非致死性中风、心血管疾病或不明原因死亡的综合症状）。

研究组共招募了4076名参与者，其中2717名接受efpeglatide治疗，1359名接受安慰剂治疗。中位随访1.81年，efpeglenatide组中有189名参与者（7.0%）发生了MACE事件（3.9件/100人-年），安慰剂组中有125名（9.2%），发生率为5.3件/100人-年，组间差异显著。Efpeglenatide组中有353名参与者（13.0%）发生综合肾结局事件（肾功能下降或蛋白尿），安慰剂组中有250名（18.4%），组间差异显著。Efpeglenatide组患者腹泻、便秘、恶心、呕吐或腹胀的发生率显著高于安慰剂组。

研究结果表明，对于有心血管疾病史或当前肾病并至少有一种其他心血管危险因素的2型糖尿病患者，每周皮下注射4或6 mg efpeglatide与安慰剂相比可显著降低心血管事件的风险。

附：英文原文

Title: Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes | NEJM

Author: Hertzel C. Gerstein, M.D.,, Naveed Sattar, M.D., Ph.D.,, Julio Rosenstock, M.D.,, Chinthanie Ramasundarahettige, M.Sc.,, Richard Pratley, M.D.,, Renato D. Lopes, M.D., Ph.D.,, Carolyn S.P. Lam, M.B., B.S., Ph.D.,, Nardev S. Khurmi, M.D.,, Laura Heenan, M.Sc.,, Stefano Del Prato, M.D.,, Leanne Dyal, M.Sc.,, and Kelley Branch, M.D.

Issue&Volume: 2021-06-28

Abstract: Background

Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain.

Methods

In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium–glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes).

Results

A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P=0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo.

Conclusions

In this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo.

DOI: 10.1056/NEJMoa2108269

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2108269