Incretin-based diabetes medications like semaglutide and tirzepatide reduce cardiovascular-damaging triglycerides and VLDL cholesterol through direct metabolic mechanisms beyond simple weight loss. The analysis reveals these drugs work by modulating intestinal fat absorption, hepatic apolipoprotein B assembly, and peripheral lipoprotein breakdown through GLP-1, GIP, glucagon, and amylin signaling pathways. Dual-hormone agonists consistently produce greater lipid improvements than single-target drugs, suggesting broader metabolic reprogramming delivers superior benefits. This mechanistic understanding helps explain why newer incretin therapies show such promising cardiovascular outcomes in clinical trials. However, significant knowledge gaps remain that could impact long-term therapeutic strategies. Most studies lack apolipoprotein B measurements, the gold standard for assessing atherogenic burden, making it difficult to quantify true cardiovascular risk reduction. Additionally, the potential for lean muscle mass loss during rapid weight loss remains understudied, which could offset metabolic benefits. The field needs longer-term trials with comprehensive body composition analysis to fully validate these drugs' cardiovascular protective mechanisms and optimize treatment protocols for different patient populations.