Translational Advances in GLP-1–Based Therapies for Cardiometabolic Disease

Cardiometabolic diseases represent a major global health burden that is driven by complex metabolic, inflammatory, and vascular dysfunctions. Traditional therapies target individual risk factors and also fail to address the integrated nature of these conditions. However, glucagon-like peptide-1 (GLP-1) receptor agonists emerged as an important therapeutic class to improve glycemic control, promote weight loss, and reduce cardiovascular risk. Recent advances have led to the development of novel long-acting, oral, and multi-receptor agonists with enhanced efficacy and improved patient adherence. These agents exert multifaceted cardiometabolic benefits via central appetite regulation, modulation of adipose and hepatic metabolism, anti-inflammatory signaling, and direct vascular and cardiac protection. Clinical trials and real-world studies demonstrate significant reductions in major adverse cardiovascular events, improved renal outcomes, and sustained metabolic function. This narrative review summarizes the evolution of GLP–1–based therapies, highlights emerging dual and triple agonists, and discusses their mechanisms, clinical implications, and safety profiles. Understanding the integrated effects of novel GLP-1 agonists may facilitate personalized treatment strategies and support their expanding role in comprehensive cardiometabolic disease management.