Incretin-based therapies are gaining momentum as a key strategy for reducing cardiovascular risk in individuals with obesity and/or type 2 diabetes (T2D). As therapeutic approaches extend beyond classical GLP-1 agonism, it remains unclear whether the cardiovascular benefits primarily reflect direct reductions in atherogenic lipoproteins—namely LDL, VLDL, and triglycerides—or broader effects mediated by weight loss, improved insulin sensitivity, and reduced ectopic adiposity. This review examines these relationships in depth. We summarize molecular, cellular, and physiological evidence describing how GLP-1, GIP, glucagon, and amylin signaling regulate intestinal lipid absorption, hepatic apoB-lipoprotein assembly, and peripheral lipoprotein catabolism. These mechanistic insights are integrated with available clinical data on single, dual, and triple incretin-based agonists and related compounds. Overall, incretin-based therapies predominantly reduce triglycerides and VLDL cholesterol, with these changes closely linked to reductions in hepatic ectopic adiposity and paralleling improvements in glycemic control, insulin sensitivity, and body weight. Agents that additionally activate glucagon or amylin pathways consistently produce greater lipid-lowering effects, supporting the concept that lipid benefits scale with global metabolic reprogramming rather than isolated receptor activation. Despite consistent lipid improvements, the short duration of most clinical trials limits assessment of long-term cardiovascular risk reduction. Moreover, the absence of apolipoprotein B data precludes definitive conclusions regarding changes in atherogenic lipoprotein burden. Uncertainty also remains regarding the preservation of lean mass during substantial weight loss. This review provides an up-to-date synthesis linking incretin pharmacology to lipid metabolism and identifies priorities for future cardiometabolic research.