James Stefan, Christoffersen Andreas Dyreborg, David Jens-Peter, Hacker Marcus, Jensen Maria D Radu Juul, Mellbin Linda, Pieber Thomas R, Ripa Rasmus Sejersten, Rossing Peter, Svehlikova Eva, Kjaer Andreas
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Novo Nordisk A/S, Aalborg, Denmark.
Am Heart J. 2025 Nov;289:17-27. doi: 10.1016/j.ahj.2025.05.001. Epub 2025 May 7.
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).
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 [F]FDG and [Ga]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) 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.
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 of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [Ga]DOTATATE (ETD: 0.045, 95% CI: -0.314;0.404).
This trial explored the feasibility of following plaque inflammation with PET-MRI using [F]FDG and [Ga]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.
URL: https://www.
gov; Unique identifier: NCT04032197.
司美格鲁肽已在患有心血管疾病（CVD）的2型糖尿病（T2D）患者中显示出心血管益处。炎症在动脉粥样硬化中起着有据可查的作用，而胰高血糖素样肽-1受体激动剂，如司美格鲁肽，在动物和临床研究中已显示出抗炎作用。本试验使用正电子发射断层扫描（PET）-磁共振成像（MRI）研究了司美格鲁肽对颈动脉粥样硬化炎症的影响。
患有T2D和CVD的患者被随机分为双盲组，每周皮下注射一次1.0 mg司美格鲁肽或安慰剂。主要和关键次要终点使用PET-MRI及[F]FDG和[Ga]DOTATATE示踪剂，以评估从基线到第26周时，颈动脉中病变最严重且通过示踪剂的最大靶本底比（TBR）对斑块炎症进行量化的节段中斑块炎症的变化。其他次要终点在第52周时使用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。
101例患者中，87.1%为男性，平均年龄66岁，且他们均按照指南进行了良好治疗。在第26周时，使用任何一种示踪剂，司美格鲁肽和安慰剂在斑块炎症变化方面均未观察到显著的治疗差异；FDG的TBR（估计治疗差异[ETD]：0.033，95%置信区间[CI]：-0.118；0.184）和[Ga]DOTATATE的TBR（ETD：0.045，95%CI：-0.314；0.404）。
本试验探索了使用[F]FDG和[Ga]DOTATATE通过PET-MRI追踪斑块炎症的可行性。通过本试验所采用的方法，未检测到司美格鲁肽与安慰剂相比对颈动脉斑块炎症有显著影响，这可能是由于基线炎症水平较低。然而，这并不排除司美格鲁肽在先前临床前和临床研究中所观察到的对炎症的影响。
网址：https://www.
gov；唯一标识符：NCT04032197。
