Effect of Once-Weekly Subcutaneous Semaglutide on Arterial Inflammation in People with Type 2 Diabetes and Cardiovascular Disease Using PET-MRI: Primary Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

IF 3.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

American heart journal Pub Date : 2025-05-07 DOI:10.1016/j.ahj.2025.05.001

Stefan James, Andreas Dyreborg Christoffersen, Jens-Peter David, Marcus Hacker, Maria D Radu Juul Jensen, Linda Mellbin, Thomas R Pieber, Rasmus Sejersten Ripa, Peter Rossing, Eva Svehlikova, Andreas Kjaer

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引用次数: 0

Abstract

Background: Semaglutide has demonstrated cardiovascular benefits in people with type 2 diabetes (T2D) with cardiovascular disease (CVD). Inflammation plays a well-documented role in atherosclerosis and glucagon-like peptide-1 receptor agonists, like semaglutide, have shown anti-inflammatory effects in animal and clinical studies. This trial investigated the effect of semaglutide on atherosclerotic inflammation in the carotid arteries using positron emission tomography (PET)-magnetic resonance imaging (MRI).

Methods: Patients with T2D and CVD were randomized to double-blinded once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary and key secondary endpoints used PET-MRI with [¹⁸F]FDG and [⁶⁸Ga]DOTATATE tracers to assess change from baseline to week 26 in plaque inflammation in the segments of the carotid arteries that were determined to be the most diseased and where plaque inflammation was quantified by the maximum target-to-background ratio (TBR_max) of the tracers. Additional secondary endpoints assessed plaque morphology and burden using MRI at week 52, including total wall volume, lipid-rich necrotic core volume, and fibrous cap thickness.

Results: Of 101 patients, 87.1% were male, mean age was 66 years and they were well-treated according to guidelines. No significant treatment differences were observed between semaglutide and placebo for change in plaque inflammation at week 26 with either tracer; TBR_max of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [⁶⁸Ga]DOTATATE (ETD: 0.045, 95% CI: -‍0.314;0.404).

Conclusions: This trial explored the feasibility of following plaque inflammation with PET-MRI using [¹⁸F]FDG and [⁶⁸Ga]DOTATATE. A significant effect of semaglutide versus placebo on carotid plaque inflammation could not be detected through the methodology used in this trial, likely due to minimal baseline inflammation. However, this does not exclude an effect of semaglutide on inflammation seen in previous preclinical and clinical studies.

Trial registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT04032197.

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每周一次皮下注射西马鲁肽对2型糖尿病和心血管疾病患者动脉炎症的影响：PET-MRI：一项随机、双盲、安慰剂对照试验的主要结果

背景：Semaglutide已被证明对伴有心血管疾病（CVD）的2型糖尿病（T2D）患者有心血管益处。炎症在动脉粥样硬化中发挥着充分的作用，而胰高血糖素样肽-1受体激动剂，如西马鲁肽，在动物和临床研究中显示出抗炎作用。本试验利用正电子发射断层扫描(PET)-磁共振成像（MRI）研究了西马鲁肽对颈动脉粥样硬化性炎症的影响。方法：T2D和CVD患者随机分为双盲组，每周一次皮下注射西马鲁肽1.0 mg或安慰剂。主要终点和关键次要终点使用PET-MRI与[18F]FDG和[68Ga]DOTATATE示踪剂，评估从基线到第26周颈动脉最病变段斑块炎症的变化，并通过示踪剂的最大靶本比（TBRmax）量化斑块炎症。其他次要终点在第52周使用MRI评估斑块形态和负荷，包括总壁体积、富含脂质的坏死核心体积和纤维帽厚度。结果：101例患者中，男性占87.1%，平均年龄66岁，均按指南治疗。在使用任何一种示踪剂的第26周，在斑块炎症的变化方面，西马鲁肽和安慰剂之间没有观察到显著的治疗差异；FDG的TBRmax（估计治疗差[ETD]: 0.033, 95%可信区间[CI]: -0.118;0.184）和[68Ga]DOTATATE （ETD: 0.045, 95% CI: -‍0.314;0.404）。结论：本试验探讨了使用[18F]FDG和[68Ga]DOTATATE对斑块炎症进行PET-MRI跟踪的可行性。通过本试验中使用的方法无法检测到西马鲁肽与安慰剂对颈动脉斑块炎症的显著影响，可能是由于基线炎症最小。然而，这并不排除在以前的临床前和临床研究中发现的西马鲁肽对炎症的影响。试用注册：网址：https://www.Clinicaltrials: gov；唯一标识符：NCT04032197。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American heart journal 医学-心血管系统

CiteScore

8.20

自引率

2.10%

发文量

214

审稿时长

38 days

期刊介绍： The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.