ObjectiveTo explore therapeutic mechanisms and clinical application prospects of novel weight-loss medications in patients with obesity complicated by cardiovascular-kidney-metabolic (CKM) syndrome, aiming to provide theoretical support and therapeutic strategies for personalized precision management of CKM syndrome. MethodsRecent domestic and international studies were retrospectively reviewed, focusing on the mechanisms of action, clinical research outcomes, and application progress of novel weight-loss medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic peptide (GIP)/GLP-1 receptor agonists, triple GIP/GLP-1/glucagon receptor agonists, and amylin analogues. Special emphasis was placed on their comprehensive effects on cardiovascular, renal, and metabolic parameters. ResultsNovel weight-loss medications had demonstrated significant weight reduction and multisystem benefits through precise regulation of central appetite pathways, insulin sensitivity, and lipid metabolism. Among these medications, GLP-1 receptor agonists (e.g., semaglutide) and dual agonists (e.g., tirzepatide) had been confirmed in phase Ⅲ clinical trials (STEP and SURMOUNT studies) to effectively reduce cardiovascular event risks, slow renal function deterioration, and markedly improve glycemic control in obese patients with CKM syndrome. Triple agonists (e.g., retatrutide) and combination therapies (e.g., cagrisema) have further enhanced weight-loss efficacy, providing novel therapeutic avenues for obesity-related diseases. Additionally, these medications usually require combined application with traditional chronic disease medications, such as sodium-glucose linked transporter 2 inhibitors and renin-angiotensin-aldosterone system blockers, to achieve comprehensive therapeutic outcomes in CKM syndrome patients. However, further studies are needed to address long-term safety in real-world settings, optimization of drug formulations, and application in precision medicine. ConclusionsNovel weight-loss medications offer promising strategies for personalized precision treatment of obesity with CKM syndrome due to their significant weight-loss efficacy and multisystem synergistic effects. Although current clinical trials demonstrate substantial therapeutic potential, the complexity of CKM syndrome and individual patient variability necessitate additional in-depth research to facilitate broader clinical adoption and optimization of these medications.