The systems medicine view of semaglutide: from clinical trials to molecular mechanisms.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Expert Review of Clinical Pharmacology Pub Date : 2026-07-01 DOI:10.1080/17512433.2026.2695172

Rui Vitorino

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引用次数: 0

Abstract

Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a key therapy in managing type 2 diabetes (T2D), offering significant improvements in glycemic control, weight loss, and cardiovascular protection. Beyond these clinical benefits, multi-omics research is clarifying the molecular mechanisms underlying its systemic metabolic effects.

Areas covered: This review synthesizes findings from major clinical trials and recent proteomic and metabolomic studies to explain how semaglutide affects inflammatory, lipid, and extracellular matrix (ECM) pathways in multiple organs. Key molecular mediators, including adiponectin, fibroblast growth factor 21 (FGF21), apolipoprotein C-III (ApoC-III), ceramides, and ECM-remodeling proteins (MMPs, CTGF, α-SMA), are linked to improved insulin sensitivity, reduced adipose inflammation, and restored metabolic flexibility. The review also discusses the use of artificial intelligence (AI) and machine learning (ML) to connect omics biomarkers with clinical outcomes.

Expert opinion: Semaglutide exemplifies a precision medicine approach for T2D by linking clinical efficacy to molecular adaptation. Longitudinal validation of omics biomarkers and their integration into AI-driven diagnostic platforms could enable personalized, mechanism-based therapy that goes beyond glucose control to deliver comprehensive cardiometabolic protection.

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西马鲁肽的系统医学观点：从临床试验到分子机制。

Semaglutide是一种胰高血糖素样肽-1受体激动剂（GLP-1RA），是治疗2型糖尿病（T2D）的关键药物，在血糖控制、体重减轻和心血管保护方面有显著改善。除了这些临床益处，多组学研究正在阐明其系统代谢作用的分子机制。涵盖领域：本综述综合了主要临床试验和最近的蛋白质组学和代谢组学研究的结果，以解释semaglutide如何影响多个器官的炎症、脂质和细胞外基质（ECM）途径。关键的分子介质，包括脂联素、成纤维细胞生长因子21 （FGF21）、载脂蛋白C-III （ApoC-III）、神经酰胺和ecm重塑蛋白（MMPs、CTGF、α-SMA），与改善胰岛素敏感性、减少脂肪炎症和恢复代谢灵活性有关。该综述还讨论了人工智能（AI）和机器学习（ML）的使用，将组学生物标志物与临床结果联系起来。专家意见：Semaglutide通过将临床疗效与分子适应联系起来，为T2D的精准医学方法提供了例证。对组学生物标志物进行纵向验证，并将其整合到人工智能驱动的诊断平台中，可以实现个性化、基于机制的治疗，超越血糖控制，提供全面的心脏代谢保护。

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

Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.30

自引率

2.30%

发文量

127

期刊介绍： Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.