Biondi Filippo, Madonna Rosalinda
Department of Pathology, Cardiology Division, University of Pisa, Via Paradisa, 56124 Pisa, Italy.
J Clin Med. 2025 Apr 15;14(8):2705. doi: 10.3390/jcm14082705.
GLP1 receptor agonists (GLP1-RAs) have become a central component in the treatment of type 2 diabetes mellitus (T2DM) and are gaining prominence in the cardiovascular field. Semaglutide and other GLP1-RA molecules possess cardioprotective properties. Cardiotoxicity, a term used to refer to cardiovascular disease caused by anticancer treatment, is a collection of common and severe conditions. Its pharmacological prevention or mitigation is a clinical unmet need as options are few and limited to some specific clinical settings. GLP1-RAs have a promising pharmacological profile given their activity on a number of pathophysiological targets and signaling pathways including oxidative stress, autophagy, and STAT3 activation. Interestingly, abnormalities in some of the GLP-1-modulated pathways have been linked to cardiotoxicity. This scoping review aims to map the extent and assess the main characteristics of research on the role of GLP1-RAs in the prevention and/or mitigation of anticancer-related cardiotoxicity. : The selection process led to the inclusion of thirteen studies chosen from reports retrieved through the search string: ("semaglutide" OR "exenatide" OR "liraglutide" OR "dulaglutide" OR "tirzepatide" OR "GLP1 receptor agonist" OR "GLP1RA" OR "GLP1-RA" OR "GLP1" OR "Glucagon-like Peptide-1 Agonists") AND ("cardioncology" OR "cardiotoxicity" OR "chemotherapy" OR "anti-cancer treatment" OR "anti-cancer therapy"). The study complied with the PRISMA guidelines on scoping reviews. : Two studies were clinical and conducted on registries, eight used animal models, two were conducted on cell cultures, and one was conducted on both animal models and cell cultures. Evidence in favor of cardioprotection and a number of putative mechanisms emerged. : Evidence on GLP1-RAs' effect on cardiotoxicity is limited in both quantity and quality and suffers from poor study standardization. However, most included studies documented a rigorously defined cardioprotective effect and demonstrated changes in several pathophysiologically relevant targets and pathways, including NF-κB, IL-6, reactive oxygen species, and caspase-3. Further clinical studies are warranted.
胰高血糖素样肽-1受体激动剂（GLP1-RAs）已成为2型糖尿病（T2DM）治疗的核心组成部分，并在心血管领域日益受到关注。司美格鲁肽和其他GLP1-RA分子具有心脏保护特性。心脏毒性是一个用于指代由抗癌治疗引起的心血管疾病的术语，是一系列常见且严重的病症。其药理预防或缓解是临床未满足的需求，因为选择很少且仅限于某些特定临床情况。鉴于GLP1-RAs对包括氧化应激、自噬和STAT3激活在内的多种病理生理靶点和信号通路具有活性，它们具有良好的药理特性。有趣的是，一些GLP-1调节途径的异常与心脏毒性有关。本综述旨在梳理GLP1-RAs在预防和/或减轻抗癌相关心脏毒性作用方面的研究范围，并评估其主要特征。：筛选过程共纳入了13项研究，这些研究选自通过搜索词检索到的报告：（“司美格鲁肽”或“艾塞那肽”或“利拉鲁肽”或“度拉鲁肽”或“替尔泊肽”或“GLP1受体激动剂”或“GLP1RA”或“GLP1-RA”或“GLP1”或“胰高血糖素样肽-1激动剂”）以及（“心脏肿瘤学”或“心脏毒性”或“化疗”或“抗癌治疗”或“抗癌疗法”）。该研究遵循了PRISMA关于综述的指南。：两项研究为临床研究且基于登记处进行，八项使用动物模型，两项在细胞培养上进行，一项同时在动物模型和细胞培养上进行。支持心脏保护作用及一些假定机制的证据出现了。：关于GLP1-RAs对心脏毒性影响的证据在数量和质量上都很有限，且研究标准化程度较差。然而，大多数纳入研究记录了严格定义的心脏保护作用，并证明了几个病理生理相关靶点和途径的变化，包括核因子κB、白细胞介素-6、活性氧和半胱天冬酶-3。有必要进行进一步的临床研究。
