Stachteas Panagiotis, Nasoufidou Athina, Karakasis Paschalis, Koiliari Markella, Karagiannidis Efstratios, Koufakis Theocharis, Fragakis Nikolaos, Patoulias Dimitrios
Second Department of Cardiology, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
Second Propedeutic Department of Internal Medicine, Aristotle University Thessaloniki, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece.
Rev Cardiovasc Med. 2025 Jul 28;26(7):39691. doi: 10.31083/RCM39691. eCollection 2025 Jul.
The global surge in cardiometabolic diseases, including type 2 diabetes, obesity, and cardiovascular diseases, has reached pandemic levels, demanding bold and innovative solutions. Dual glucagon (Gcg) and glucagon-like peptide-1 (GLP-1) receptor agonists represent a groundbreaking advancement in the treatment of this complex and interconnected spectrum of disorders. By harnessing the synergistic power of GLP-1 and Gcg receptor activation, these agents go beyond glucose lowering and weight loss, unlocking new frontiers in energy expenditure, fat oxidation, and liver fat reduction-key targets in conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD). Emerging clinical evidence on agents such as survodutide and cotadutide has revealed striking improvements in glycated hemoglobin (HbA1c) levels and body weight, consistently outperforming traditional GLP-1 receptor agonists. More importantly, early evidence suggests meaningful benefits in cardiovascular and renal outcomes, positioning these therapies as comprehensive, disease-modifying tools for patients with multiple high-risk comorbidities. This review highlights the transformative potential of dual GLP-1/Gcg receptor agonists, providing a thorough examination of their mechanisms of action, clinical efficacy, and safety profiles across the cardio-metabolic continuum. As the limitations of existing therapies become increasingly evident, these next-generation agents are poised to redefine the standard of care across the cardiometabolic continuum, ushering in a new era of precision medicine for metabolic disease.
包括2型糖尿病、肥胖症和心血管疾病在内的心脏代谢疾病在全球范围内激增，已达到大流行程度，这需要大胆创新的解决方案。双重胰高血糖素（Gcg）和胰高血糖素样肽-1（GLP-1）受体激动剂代表了在治疗这一复杂且相互关联的疾病谱方面的一项突破性进展。通过利用GLP-1和Gcg受体激活的协同作用，这些药物不仅能降低血糖和减轻体重，还在能量消耗、脂肪氧化和减少肝脏脂肪方面开辟了新领域，而这些正是代谢功能障碍相关脂肪性肝病（MASLD）等疾病的关键靶点。关于司伏鲁肽和可他鲁肽等药物的新出现的临床证据显示，糖化血红蛋白（HbA1c）水平和体重有显著改善，始终优于传统的GLP-1受体激动剂。更重要的是，早期证据表明在心血管和肾脏结局方面有显著益处，使这些疗法成为患有多种高风险合并症患者的全面、改善疾病的工具。本综述强调了双重GLP-1/Gcg受体激动剂的变革潜力，全面审视了它们在心脏代谢连续统一体中的作用机制、临床疗效和安全性。随着现有疗法的局限性日益明显，这些下一代药物有望重新定义心脏代谢连续统一体的治疗标准，开创代谢疾病精准医学的新时代。
