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VSMC phenotypic switching is characterized by transformation from a quiescent contractile to an activated synthetic phenotype, promoting proliferation and leading to the formation of the neointima, the pathological vascular compartment critical for the development of atherosclerosis

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This triple mechanism distinguishes retatrutide from existing approved weight loss peptides such as semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GIP/GLP-1 receptor agonist), although direct head-to-head trials comparing these agents have not been conducted, and comparative efficacy has not been established

Glucagon is classically viewed as a fasting and counter-regulatory hormone that increases hepatic glucose output through glycogenolysis and gluconeogenesis