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Semaglutide, a diabetes drug, can also reduce alcohol consumption by modulating the brains reward and punishment systems GLP-1RAs in the cardiovascular system In the cardiovascular system, GLP-1 can reduce cardiac ischemia-reperfusion injury through the activation of specific signaling pathways, such as the PI3K/Akt pathway.437,438 This involves modulating the cell apoptosis process, for example, by decreasing the Bax/Bcl-2 ratio in cardiomyocytes, reducing cytochrome C release, and caspase activation.438,439 GLP-1 can also enhance endothelial function by promoting the production of NO, possibly through activating eNOS, thereby affecting vasodilation, anti-inflammatory actions, and anti-atherosclerosis.43,192,440,441 GLP-1RAs and AS AS is characterized by the formation of fibrofatty plaques within arterial walls and is one of the foremost global causes of mortality.5 GLP-1RAs, as exemplified by liraglutide and semaglutide, exhibit pronounced cardiovascular protective effects.43 Liraglutide and semaglutide have been demonstrated to be effective at reducing lipid and blood pressure levels through numerous scientific investigations, thereby contributing to the mitigation of AS and cardiovascular ailments.442 Preclinical studies have documented the inhibitory effects of GLP-1RAs on the development of AS in animal models.443 These agents exert their anti-atherosclerotic effects through various mechanisms, including by improving blood lipid profiles,444 preserving endothelial integrity and regulating endothelial function,445 as well as modulating inflammatory processes.70 GLP-1RAs confer substantial benefits for individuals with AS owing to their multifaceted impact on various aspects of cardiovascular health.39,40,446 Notably, GLP-1RAs exhibit pronounced efficacy in optimizing blood lipid profiles by effectively suppressing chylomicron secretion in the intestine, thereby mitigating the occurrence of postprandial hyperlipidemia.447 Moreover, these agents promote hemodynamic equilibrium,18 diminish thrombotic propensity,448 alleviate endothelial oxidative stress,449 attenuate inflammatory processes,450 and foster a favorable balance of the gut microbiota,451 all of which collectively contribute to the salutary effects of these agents in patients with AS

Clinicians should judiciously balance potential benefits against risks when considering the use of these agents in pregnant patients and, where feasible, engage in thorough preconception counseling.225,226 Future research should prioritize the evaluation of long-term safety outcomes during pregnancy and potential fetal effects to inform safer clinical practices
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