加拿大多伦多综合医院Mansoor Husain团队取得一项新突破，他们探讨了2型糖尿病患者口服Semaglutide和心血管结局的关联。 相关论文2019年8月29日发表在国际顶尖医学期刊《新英格兰医学杂志》上。

在这项事件驱动、随机、双盲、安慰剂对照试验中，研究组共招募了3183名患者，平均年龄为66岁，84.7%年龄超过50岁，患有心血管病或慢性肾病，随机分为口服Semaglutide组（1591名）和安慰剂组（1592名）。严重的心血管不良事件包括心血管原因导致的死亡、非致命性心肌梗死或非致命性卒中。

该试验的平均时间为15.9个月。Semaglutide组中有61名患者（3.8%）发生了严重的心血管不良事件，安慰剂组中有76名（4.8%），风险比为0.79，差异无统计学意义。其中，Semaglutide组心血管原因所致的死亡有15例（0.9%），安慰剂组有30例（1.9%），风险比为0.49；Semaglutide组非致命性心肌梗死37例（2.3%），安慰剂组31例（1.9%），风险比为1.18；Semaglutide组非致命性中风12例（0.8%），安慰剂组16例（1.0%），风险比为0.74。Semaglutide组共有23名患者（1.4%）死亡，安慰剂组共有45名患者（2.8%）死亡，风险比为0.51。两组中均有因胃肠道不良反应而停止服药的患者，但在Semaglutide组中更为常见。

在这项涉及2型糖尿病患者的试验中，口服Semaglutide的心血管危险性并不低于安慰剂。

据悉，2型糖尿病新疗法的心血管安全性尤为重要。皮下注射胰高血糖素样肽-1受体激动剂Semaglutide已被证实安全，但口服Semaglutide的安全性仍有待商榷。

附：英文原文

Title: Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

Author: Mansoor Husain, Andreas L. Birkenfeld, Morten Donsmark, et al

Issue&Volume: Vol 381 No 9, 29 August 2019

Abstract:

BACKGROUND

Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide.

METHODS
We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome).

RESULTS
A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide.

CONCLUSIONS
In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716. )

DOI: 10.1056/NEJMoa1901118

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1901118